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FDA approves drug to treat 2 types of AML
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com. 
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com.
The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.
The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.
The company says the drug will be commercially available within a week.
The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
For more information on CPX-351, visit http://www.vyxeos.com.
FDA approves first treatment for cGVHD
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
FDA grants drug orphan designation for PNH
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA approves enasidenib to treat relapsed/refractory AML
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).
The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.
Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.
The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.
Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.
Companion diagnostic
Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.
The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.
Enasidenib is licensed from Agios Pharmaceuticals.
Trial results
The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).
Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.
The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.
The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.
The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.
The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).
For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).
The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.
Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.
FDA grants acalabrutinib breakthrough designation
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.
The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.
Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.
ASCO updates guidelines on antiemetic use in cancer patients
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.
The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.
“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.
“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”
To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.
“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.
“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”
Key recommendations in the updated guidelines include:
For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.
For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).
Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.
Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.
FDA grants drug breakthrough designation for AML
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).
The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About venetoclax
Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.
Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.
The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.
They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.
The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.
The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.
The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).
Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).
The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About venetoclax
Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.
Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.
The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.
They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.
The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.
The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.
The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).
Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).
The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About venetoclax
Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.
Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.
The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.
They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.
The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.
The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.
The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).
Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).
Product granted fast track designation for aTTP
The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About caplacizumab
Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.
Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.
The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.
The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).
The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.
There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.
There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.
The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.
A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.
In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.
There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.
Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.
The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About caplacizumab
Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.
Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.
The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.
The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).
The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.
There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.
There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.
The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.
A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.
In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.
There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.
Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.
The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
About caplacizumab
Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.
Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.
The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.
The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).
The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.
There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.
There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.
The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.
A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.
In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.
There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.
Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.
Health Canada approves new use for brentuximab vedotin
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).
Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).
This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.
Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.
Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.
AETHERA trial
Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.
The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).
FDA grants orphan designation to gilteritinib in AML
The US Food and Drug Administration (FDA) has granted orphan drug designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib, an inhibitor of FLT3 and AXL, has demonstrated activity against FLT3 internal tandem duplication (ITD) as well as tyrosine kinase domain, 2 mutations that are seen in up to a third of patients with AML.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were presented at the 2017 ASCO Annual Meeting.
The goal of the study was to determine the tolerability and antileukemic activity of once-daily gilteritinib in a FLT3-ITD-enriched, relapsed/refractory AML population.
The drug exhibited “potent” FLT3 inhibition at doses greater than 80 mg/day. In patients who received such doses, the greatest overall response rate was 52%, and the longest median overall survival was 31 weeks.
The maximum tolerated dose of gilteritinib was 300 mg/day. Dose-limiting toxicities included diarrhea and liver function abnormalities.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib, an inhibitor of FLT3 and AXL, has demonstrated activity against FLT3 internal tandem duplication (ITD) as well as tyrosine kinase domain, 2 mutations that are seen in up to a third of patients with AML.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were presented at the 2017 ASCO Annual Meeting.
The goal of the study was to determine the tolerability and antileukemic activity of once-daily gilteritinib in a FLT3-ITD-enriched, relapsed/refractory AML population.
The drug exhibited “potent” FLT3 inhibition at doses greater than 80 mg/day. In patients who received such doses, the greatest overall response rate was 52%, and the longest median overall survival was 31 weeks.
The maximum tolerated dose of gilteritinib was 300 mg/day. Dose-limiting toxicities included diarrhea and liver function abnormalities.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib, an inhibitor of FLT3 and AXL, has demonstrated activity against FLT3 internal tandem duplication (ITD) as well as tyrosine kinase domain, 2 mutations that are seen in up to a third of patients with AML.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were presented at the 2017 ASCO Annual Meeting.
The goal of the study was to determine the tolerability and antileukemic activity of once-daily gilteritinib in a FLT3-ITD-enriched, relapsed/refractory AML population.
The drug exhibited “potent” FLT3 inhibition at doses greater than 80 mg/day. In patients who received such doses, the greatest overall response rate was 52%, and the longest median overall survival was 31 weeks.
The maximum tolerated dose of gilteritinib was 300 mg/day. Dose-limiting toxicities included diarrhea and liver function abnormalities.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.