FDA/CDC

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration is investigating whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers.

Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.

Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.

Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.

Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).

“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.

Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration is investigating whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers.

Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.

Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.

Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.

Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).

“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.

Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration is investigating whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers.

Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.

Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.

Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.

Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).

“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.

Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

A version of this article first appeared on Medscape.com.

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine