Pharmacy

Prescription medications

Credit: Steven Harbour

The US Food and Drug Administration (FDA) has launched a program that allows certain companies to expedite the importation of drugs and drug ingredients.

Thirteen companies have been selected to take part in this 2-year program, called the Secure Supply Chain Pilot Program.

As the companies meet certain criteria, they are eligible to receive expedited entry for up to 5 drug products. These products can enter the US after electronic screening without undergoing human examination.

The FDA said its goal with this program is to allow the agency to focus its imports surveillance resources on preventing the entry of drugs that are most likely to compromise the quality and safety of the US drug supply.

The companies that have been accepted into the program are:

• AbbVie Inc.
• Allergan, Inc.
• Astellas U.S. Technologies, Inc.
• Bristol-Myers Squibb Company
• Celgene Corporation
• GE Healthcare Inc.
• GlaxoSmithKline LLC
• Merck Sharp & Dohme Corporation
• Mylan Pharmaceuticals Inc.
• Novartis Pharmaceuticals Corporation
• Pfizer, Inc.
• Teva Pharmaceutcials USA, Inc.
• Watson Laboratories, Inc.

Each of these companies met the participation conditions, including:

• Committing to comply with requirements of the Food, Drug, and Cosmetics Act (FDCA)
• Having a validated, secure supply chain protocol per the US Customs and Border Protection’s Customs-Trade Partnership Against Terrorism (C-TPAT) program
• Having a plan in place to quickly correct potential problems the FDA identifies regarding importation of specific products
• Having effective recall and corrective action plans in place
• Maintaining control over their drugs from the time of manufacture abroad through entry into the US.

Over the next 2 years, the FDA will evaluate whether this program enhances imported drug compliance with FDA regulations and the security of the drug supply chain. If the FDA deems the program effective, a more permanent program may be established and possibly extended to additional companies.

For more information, see the FDA’s notice about the program, published in the Federal Register last August.

Prescription medications

Credit: Steven Harbour

The US Food and Drug Administration (FDA) has launched a program that allows certain companies to expedite the importation of drugs and drug ingredients.

Thirteen companies have been selected to take part in this 2-year program, called the Secure Supply Chain Pilot Program.

As the companies meet certain criteria, they are eligible to receive expedited entry for up to 5 drug products. These products can enter the US after electronic screening without undergoing human examination.

The FDA said its goal with this program is to allow the agency to focus its imports surveillance resources on preventing the entry of drugs that are most likely to compromise the quality and safety of the US drug supply.

The companies that have been accepted into the program are:

• AbbVie Inc.
• Allergan, Inc.
• Astellas U.S. Technologies, Inc.
• Bristol-Myers Squibb Company
• Celgene Corporation
• GE Healthcare Inc.
• GlaxoSmithKline LLC
• Merck Sharp & Dohme Corporation
• Mylan Pharmaceuticals Inc.
• Novartis Pharmaceuticals Corporation
• Pfizer, Inc.
• Teva Pharmaceutcials USA, Inc.
• Watson Laboratories, Inc.

Each of these companies met the participation conditions, including:

• Committing to comply with requirements of the Food, Drug, and Cosmetics Act (FDCA)
• Having a validated, secure supply chain protocol per the US Customs and Border Protection’s Customs-Trade Partnership Against Terrorism (C-TPAT) program
• Having a plan in place to quickly correct potential problems the FDA identifies regarding importation of specific products
• Having effective recall and corrective action plans in place
• Maintaining control over their drugs from the time of manufacture abroad through entry into the US.

Over the next 2 years, the FDA will evaluate whether this program enhances imported drug compliance with FDA regulations and the security of the drug supply chain. If the FDA deems the program effective, a more permanent program may be established and possibly extended to additional companies.

For more information, see the FDA’s notice about the program, published in the Federal Register last August.

Prescription medications

Credit: Steven Harbour

The US Food and Drug Administration (FDA) has launched a program that allows certain companies to expedite the importation of drugs and drug ingredients.

Thirteen companies have been selected to take part in this 2-year program, called the Secure Supply Chain Pilot Program.

As the companies meet certain criteria, they are eligible to receive expedited entry for up to 5 drug products. These products can enter the US after electronic screening without undergoing human examination.

The FDA said its goal with this program is to allow the agency to focus its imports surveillance resources on preventing the entry of drugs that are most likely to compromise the quality and safety of the US drug supply.

The companies that have been accepted into the program are:

• AbbVie Inc.
• Allergan, Inc.
• Astellas U.S. Technologies, Inc.
• Bristol-Myers Squibb Company
• Celgene Corporation
• GE Healthcare Inc.
• GlaxoSmithKline LLC
• Merck Sharp & Dohme Corporation
• Mylan Pharmaceuticals Inc.
• Novartis Pharmaceuticals Corporation
• Pfizer, Inc.
• Teva Pharmaceutcials USA, Inc.
• Watson Laboratories, Inc.

Each of these companies met the participation conditions, including:

• Committing to comply with requirements of the Food, Drug, and Cosmetics Act (FDCA)
• Having a validated, secure supply chain protocol per the US Customs and Border Protection’s Customs-Trade Partnership Against Terrorism (C-TPAT) program
• Having a plan in place to quickly correct potential problems the FDA identifies regarding importation of specific products
• Having effective recall and corrective action plans in place
• Maintaining control over their drugs from the time of manufacture abroad through entry into the US.

Over the next 2 years, the FDA will evaluate whether this program enhances imported drug compliance with FDA regulations and the security of the drug supply chain. If the FDA deems the program effective, a more permanent program may be established and possibly extended to additional companies.

For more information, see the FDA’s notice about the program, published in the Federal Register last August.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Drug in vials

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted full approval of omacetaxine mepesuccinate (Synribo) for the treatment of chronic myeloid leukemia (CML).

The drug received accelerated approval in October 2012 to treat adults with chronic phase (CP) or accelerated phase (AP) CML who were resistant to or could not tolerate 2 or more tyrosine kinase inhibitors (TKIs).

But additional clinical trial data were required before the FDA could grant the drug full approval.

Now, the agency has granted that approval based on the final analysis of two phase 2 trials.

The original approval of omacetaxine mepesuccinate was based on an analysis of combined data subsets from these trials. The pooled analysis included patients who had received 2 or more approved TKIs and, at a minimum, had evidence of resistance or intolerance to dasatinib and/or nilotinib.

Forty-seven percent of patients with CP CML and 63% of patients with AP CML had failed treatment with 3 TKIs—imatinib, dasatinib, and nilotinib. The majority of patients had also received other treatments, including hydroxyurea, interferon, and cytarabine.

Among CP patients, 18% (14/76) achieved a major cytogenetic response (MCyR). The mean time to MCyR onset was 3.5 months, and the median duration of MCyR was 12.5 months.

Among AP Patients, 14% (5/35) achieved a major hematologic response (MaHR). The mean time to MaHR onset was 2.3 months, and the median duration of MaHR was 4.7 months.

The most common adverse events for AP and CP patients (occurring in 20% or more) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia.

Omacetaxine mepesuccinate is the first protein synthesis inhibitor for CML. Although the drug’s mechanism of action is not fully understood, it is known to prevent the production of Bcr-Abl and Mcl-1, which help drive CML.

For more details on omacetaxine mepesuccinate, see the full prescribing information.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

Thrombus

Credit: Andre E.X. Brown

The US Food and Drug Administration (FDA) has again decided not to approve the anticoagulant rivaroxaban (Xarelto) for use in patients with acute coronary syndromes (ACS).

The drug’s developers are seeking approval of rivaroxaban to reduce the risk of secondary cardiovascular events—heart attack, stroke, or death—and to reduce the risk of stent thrombosis in ACS patients.

For both indications, the drug would be given in combination with standard antiplatelet therapy.

This is not the first time the FDA has decided against approving rivaroxaban for use in ACS patients. The agency rejected the drug as prophylaxis for cardiovascular events in June 2012 and March 2013. And the drug was denied approval for stent thrombosis in June 2013.

Nevertheless, it seems the companies developing rivaroxaban—Janssen Research & Development, LLC and Bayer HealthCare—plan to continue pursuing approvals for these indications.

“We remain committed to providing patients who have suffered from acute coronary syndrome with additional protection against stent thrombosis and secondary, life-threatening cardiovascular events,” said Paul Burton, MD, PhD, Vice President, Clinical Development, Janssen Research & Development.

“We are evaluating the contents of the [FDA’s complete response] letters and will determine the appropriate next steps.”

Both applications for expanding rivaroxaban use were based on results from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in November 2011.

The study showed that rivaroxaban, when given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients, compared to placebo. But rivaroxaban also increased the risk of major bleeding and intracranial hemorrhage.

In past evaluations of rivaroxaban, the FDA and its advisors expressed concerns about data from this trial, particularly the risk of bleeding associated with rivaroxaban and some gaps in trial data.

Although Janssen submitted the missing data, the FDA still had reservations about rivaroxaban’s safety and efficacy in ACS patients. The FDA recently suggested the company limit the proposed duration of rivaroxaban treatment, as the drug might be safer and more effective when given for a shorter period.

So Janssen changed the suggested treatment duration to 90 days. But last month, an FDA advisory committee still recommended against expanding the drug’s indication. And the agency seems to have taken that recommendation to heart.

Rivaroxaban is currently FDA-approved to treat patients with venous thromboembolism (VTE) and to reduce the risk of VTE recurrence following an initial 6-month treatment for acute VTE. The drug is also approved for use as thromboprophylaxis for patients with non-valvular atrial fibrillation, those who have undergone knee replacement surgery, and patients who have had hip replacement surgery.

Patient consults with pharmacist

Credit: Rhoda Baer

The US Food and Drug Administration (FDA) has expanded the indication for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica).

Last November, the drug gained accelerated approval as a “breakthrough therapy” for patients with mantle cell lymphoma who had received at least 1 prior therapy.

Now, ibrutinib has been granted accelerated approval to treat patients with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy.

The accelerated approval process allows the FDA to approve a drug based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Both approvals of ibrutinib are based on observed benefits in overall response rates.

Ibrutinib also received priority review and orphan-product designation for CLL.

Trial results

The accelerated approval of ibrutinib is based on results of a phase 1b/2 study, which included 48 patients with relapsed or refractory CLL. The patients had been diagnosed an average of 6.7 years prior to study enrollment and had received 4 prior therapies.

All patients received 420 mg of ibrutinib orally until disease progression or the development of unacceptable toxicity.

The overall response rate was 58.3%, and all of these were partial responses. The median duration of response was not reached (range, 5.6 months to more than 24.2 months).

Study investigators have not established whether ibrutinib confers improvements in survival or disease-related symptoms.

The median treatment duration was 15.6 months. Ten percent of patients (n=5) discontinued treatment due to adverse events. Three of these patients developed infections, and 2 had subdural hematomas. Thirteen percent of patients experienced adverse events that led to dose reductions.

The most commonly occurring adverse events (all grades and grade 3/4, respectively) included thrombocytopenia (71%, 10%), diarrhea (63%, 4%), bruising (54%, 2%), neutropenia (54%, 27%), anemia (44%, 0%), upper respiratory tract infection (48%, 26%), fatigue (31%, 4%), musculoskeletal pain (27%, 6%), rash (27%, 0%), pyrexia (25%, 2%), constipation (23%, 2%), peripheral edema (23%, 0%), arthralgia (23%, 0%), nausea (21%, 2%), stomatitis (21%, 0%), sinusitis (21%, 6%), and dizziness (21%, 0%).

Ibrutinib is being developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. For full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

Patient consults with pharmacist

Credit: Rhoda Baer

The US Food and Drug Administration (FDA) has expanded the indication for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica).

Last November, the drug gained accelerated approval as a “breakthrough therapy” for patients with mantle cell lymphoma who had received at least 1 prior therapy.

Now, ibrutinib has been granted accelerated approval to treat patients with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy.

The accelerated approval process allows the FDA to approve a drug based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Both approvals of ibrutinib are based on observed benefits in overall response rates.

Ibrutinib also received priority review and orphan-product designation for CLL.

Trial results

The accelerated approval of ibrutinib is based on results of a phase 1b/2 study, which included 48 patients with relapsed or refractory CLL. The patients had been diagnosed an average of 6.7 years prior to study enrollment and had received 4 prior therapies.

All patients received 420 mg of ibrutinib orally until disease progression or the development of unacceptable toxicity.

The overall response rate was 58.3%, and all of these were partial responses. The median duration of response was not reached (range, 5.6 months to more than 24.2 months).

Study investigators have not established whether ibrutinib confers improvements in survival or disease-related symptoms.

The median treatment duration was 15.6 months. Ten percent of patients (n=5) discontinued treatment due to adverse events. Three of these patients developed infections, and 2 had subdural hematomas. Thirteen percent of patients experienced adverse events that led to dose reductions.

The most commonly occurring adverse events (all grades and grade 3/4, respectively) included thrombocytopenia (71%, 10%), diarrhea (63%, 4%), bruising (54%, 2%), neutropenia (54%, 27%), anemia (44%, 0%), upper respiratory tract infection (48%, 26%), fatigue (31%, 4%), musculoskeletal pain (27%, 6%), rash (27%, 0%), pyrexia (25%, 2%), constipation (23%, 2%), peripheral edema (23%, 0%), arthralgia (23%, 0%), nausea (21%, 2%), stomatitis (21%, 0%), sinusitis (21%, 6%), and dizziness (21%, 0%).

Ibrutinib is being developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. For full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

Patient consults with pharmacist

Credit: Rhoda Baer

The US Food and Drug Administration (FDA) has expanded the indication for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica).

Last November, the drug gained accelerated approval as a “breakthrough therapy” for patients with mantle cell lymphoma who had received at least 1 prior therapy.

Now, ibrutinib has been granted accelerated approval to treat patients with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy.

The accelerated approval process allows the FDA to approve a drug based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Both approvals of ibrutinib are based on observed benefits in overall response rates.

Ibrutinib also received priority review and orphan-product designation for CLL.

Trial results

The accelerated approval of ibrutinib is based on results of a phase 1b/2 study, which included 48 patients with relapsed or refractory CLL. The patients had been diagnosed an average of 6.7 years prior to study enrollment and had received 4 prior therapies.

All patients received 420 mg of ibrutinib orally until disease progression or the development of unacceptable toxicity.

The overall response rate was 58.3%, and all of these were partial responses. The median duration of response was not reached (range, 5.6 months to more than 24.2 months).

Study investigators have not established whether ibrutinib confers improvements in survival or disease-related symptoms.

The median treatment duration was 15.6 months. Ten percent of patients (n=5) discontinued treatment due to adverse events. Three of these patients developed infections, and 2 had subdural hematomas. Thirteen percent of patients experienced adverse events that led to dose reductions.

The most commonly occurring adverse events (all grades and grade 3/4, respectively) included thrombocytopenia (71%, 10%), diarrhea (63%, 4%), bruising (54%, 2%), neutropenia (54%, 27%), anemia (44%, 0%), upper respiratory tract infection (48%, 26%), fatigue (31%, 4%), musculoskeletal pain (27%, 6%), rash (27%, 0%), pyrexia (25%, 2%), constipation (23%, 2%), peripheral edema (23%, 0%), arthralgia (23%, 0%), nausea (21%, 2%), stomatitis (21%, 0%), sinusitis (21%, 6%), and dizziness (21%, 0%).

Ibrutinib is being developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. For full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

Prescription medications

Credit: CDC

Health Canada has approved pomalidomide (Pomalyst) for use in combination with dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM).

Patients must have received at least 2 prior therapies, failed treatment with lenalidomide and bortezomib, and experienced disease progression while on their last treatment regimen.

Health Canada had given pomalidomide priority review status due to the unmet need of effective therapies for patients with aggressive MM.

“Until now, there have been no approved options for patients whose disease has progressed despite available treatments,” said Donna E. Reece, MD, of the Princess Margaret Cancer Centre in Toronto.

“With Pomalyst, we have a new option that extends periods of remission, is generally well-tolerated, and can be taken in the convenience of a patient’s home.”

Trial prompts approval

Health Canada based its approval of pomalidomide on findings from the MM-003 trial. Regulatory agencies in the United States and European Union, both of which approved pomalidomide last year, based their decisions on the results of this study as well.

The phase 3 trial included 455 patients with relapsed or refractory MM who had received a median of 5 prior treatment regimens.

Patients were randomized to receive pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone alone (HiDEX, n=153). The median follow-up was 10 months.

Researchers found that response and survival rates were superior in the POM-LoDEX arm, and rates of adverse events were largely similar between the 2 arms.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months and 6.1 months, respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar.

Rates of grade 3/4 non-hematologic toxicities were also comparable and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

These results were presented at the 2013 ASCO Annual Meeting and published in The Lancet Oncology in October.

Drug availability

Pomalidomide is expected to be commercially available in Canada in March.

The drug will be distributed through a risk-management program called RevAid, which was developed in 2008. By adding pomalidomide to the program, regulators are aiming to prevent fetal exposure to the drug because of its structural similarities to thalidomide, a known human teratogen.

Under the program, only prescribers and pharmacists registered with RevAid are able to prescribe and dispense pomalidomide. In addition, only those patients who are registered and meet all the conditions of the RevAid program will receive the drug.

Prescription medications

Credit: CDC

Health Canada has approved pomalidomide (Pomalyst) for use in combination with dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM).

Patients must have received at least 2 prior therapies, failed treatment with lenalidomide and bortezomib, and experienced disease progression while on their last treatment regimen.

Health Canada had given pomalidomide priority review status due to the unmet need of effective therapies for patients with aggressive MM.

“Until now, there have been no approved options for patients whose disease has progressed despite available treatments,” said Donna E. Reece, MD, of the Princess Margaret Cancer Centre in Toronto.

“With Pomalyst, we have a new option that extends periods of remission, is generally well-tolerated, and can be taken in the convenience of a patient’s home.”

Trial prompts approval

Health Canada based its approval of pomalidomide on findings from the MM-003 trial. Regulatory agencies in the United States and European Union, both of which approved pomalidomide last year, based their decisions on the results of this study as well.

The phase 3 trial included 455 patients with relapsed or refractory MM who had received a median of 5 prior treatment regimens.

Patients were randomized to receive pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone alone (HiDEX, n=153). The median follow-up was 10 months.

Researchers found that response and survival rates were superior in the POM-LoDEX arm, and rates of adverse events were largely similar between the 2 arms.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months and 6.1 months, respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar.

Rates of grade 3/4 non-hematologic toxicities were also comparable and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

These results were presented at the 2013 ASCO Annual Meeting and published in The Lancet Oncology in October.

Drug availability

Pomalidomide is expected to be commercially available in Canada in March.

The drug will be distributed through a risk-management program called RevAid, which was developed in 2008. By adding pomalidomide to the program, regulators are aiming to prevent fetal exposure to the drug because of its structural similarities to thalidomide, a known human teratogen.

Under the program, only prescribers and pharmacists registered with RevAid are able to prescribe and dispense pomalidomide. In addition, only those patients who are registered and meet all the conditions of the RevAid program will receive the drug.

Prescription medications

Credit: CDC

Health Canada has approved pomalidomide (Pomalyst) for use in combination with dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM).

Patients must have received at least 2 prior therapies, failed treatment with lenalidomide and bortezomib, and experienced disease progression while on their last treatment regimen.

Health Canada had given pomalidomide priority review status due to the unmet need of effective therapies for patients with aggressive MM.

“Until now, there have been no approved options for patients whose disease has progressed despite available treatments,” said Donna E. Reece, MD, of the Princess Margaret Cancer Centre in Toronto.

“With Pomalyst, we have a new option that extends periods of remission, is generally well-tolerated, and can be taken in the convenience of a patient’s home.”

Trial prompts approval

Health Canada based its approval of pomalidomide on findings from the MM-003 trial. Regulatory agencies in the United States and European Union, both of which approved pomalidomide last year, based their decisions on the results of this study as well.

The phase 3 trial included 455 patients with relapsed or refractory MM who had received a median of 5 prior treatment regimens.

Patients were randomized to receive pomalidomide plus low-dose dexamethasone (POM-LoDEX, n=302) or high-dose dexamethasone alone (HiDEX, n=153). The median follow-up was 10 months.

Researchers found that response and survival rates were superior in the POM-LoDEX arm, and rates of adverse events were largely similar between the 2 arms.

The overall response rate was 31% (n=95) in the POM-LoDEX arm and 10% (n=15) in the HiDEX arm. The median duration of response was 7.0 months and 6.1 months, respectively.

The median progression-free survival was 4.0 months in the POM-LoDEX arm and 1.9 months in the HiDEX arm (P<0.001). And the median overall survival was 12.7 months in the POM-LoDEX arm and 8.1 months in the HiDEX arm (P=0.028).

Patients in the POM-LoDEX arm experienced more grade 3/4 neutropenia than patients in the HiDEX arm. But rates of grade 3/4 anemia and thrombocytopenia were similar.

Rates of grade 3/4 non-hematologic toxicities were also comparable and included infection, pneumonia, hemorrhage, glucose intolerance, and fatigue. Other adverse events of note included venous thromboembolism and peripheral neuropathy, which occurred at similar rates in both arms.

These results were presented at the 2013 ASCO Annual Meeting and published in The Lancet Oncology in October.

Drug availability

Pomalidomide is expected to be commercially available in Canada in March.

The drug will be distributed through a risk-management program called RevAid, which was developed in 2008. By adding pomalidomide to the program, regulators are aiming to prevent fetal exposure to the drug because of its structural similarities to thalidomide, a known human teratogen.

Under the program, only prescribers and pharmacists registered with RevAid are able to prescribe and dispense pomalidomide. In addition, only those patients who are registered and meet all the conditions of the RevAid program will receive the drug.

Nurse hangs bags filled

with chemotherapy drugs

Credit: Bill Branson

A group of healthcare experts has created a “blueprint” for managing and preventing drug shortages.

They devised 6 recommendations for preempting shortages of pediatric oncology drugs, but the suggestions can be applied to other drugs as well.

Some of the recommendations would represent new norms for healthcare practice, such as sharing scarce drugs among healthcare institutions and not giving preferential access to patients participating in clinical trials.

The suggestions appear in a consensus statement published in Pediatrics.

“Although our recommendations were developed with pediatric oncology in mind, and serve as a blueprint for preventing children with cancer from lacking access to essential life-saving medications, we believe that they apply more broadly across medicine to include pediatrics and adult medicine in general,” said statement author Yoram Unguru, MD, of the Johns Hopkins Berman Institute of Bioethics in Baltimore, Maryland.

He and his coauthors developed the following recommendations:

1. Support national polices—and develop new measures—to prevent drug shortages
2. Use drug supplies efficiently to reduce the likelihood of shortages
3. Give equal priority to evidence-based uses of drugs, whether they occur within or outside clinical trials
4. Develop an improved clearinghouse for sharing drug shortage information
5. Explore the sharing of drug supplies among institutions
6. Develop strategies to engage stakeholders in the management of drug shortages.

For each recommendation, the authors included potential barriers to its implementation. A centralized information source of drug supply information, for instance, comes with the risk that such information will encourage hoarding of existing supplies. This includes “gray market” suppliers that sell scarce drugs for inflated prices.

The authors also pointed to the marketplace economy as an obstacle to implementing their recommendations and preventing drug shortages. Drug manufacturers do not like to disclose manufacturing problems that lead to shortages, nor are competitive healthcare institutions accustomed to cooperating to share resources.

Nonetheless, the authors called for an exploration of “ways to facilitate inter-institutional and inter-state transfer of drugs, especially during shortages,” as well as the ethical obligation to patients inside vs outside a healthcare institution when there is a drug shortage.

“The reasons for drug shortages are complex, but we must not lose sight of the fact that, without access to these life-saving drugs, children and adults with cancer will almost certainly die,” Dr Unguru said. “It is untenable for this situation to continue any longer. We have a clear moral obligation to act to address this critical issue.”

Nurse hangs bags filled

with chemotherapy drugs

Credit: Bill Branson

A group of healthcare experts has created a “blueprint” for managing and preventing drug shortages.

They devised 6 recommendations for preempting shortages of pediatric oncology drugs, but the suggestions can be applied to other drugs as well.

Some of the recommendations would represent new norms for healthcare practice, such as sharing scarce drugs among healthcare institutions and not giving preferential access to patients participating in clinical trials.

The suggestions appear in a consensus statement published in Pediatrics.

“Although our recommendations were developed with pediatric oncology in mind, and serve as a blueprint for preventing children with cancer from lacking access to essential life-saving medications, we believe that they apply more broadly across medicine to include pediatrics and adult medicine in general,” said statement author Yoram Unguru, MD, of the Johns Hopkins Berman Institute of Bioethics in Baltimore, Maryland.

He and his coauthors developed the following recommendations:

1. Support national polices—and develop new measures—to prevent drug shortages
2. Use drug supplies efficiently to reduce the likelihood of shortages
3. Give equal priority to evidence-based uses of drugs, whether they occur within or outside clinical trials
4. Develop an improved clearinghouse for sharing drug shortage information
5. Explore the sharing of drug supplies among institutions
6. Develop strategies to engage stakeholders in the management of drug shortages.

For each recommendation, the authors included potential barriers to its implementation. A centralized information source of drug supply information, for instance, comes with the risk that such information will encourage hoarding of existing supplies. This includes “gray market” suppliers that sell scarce drugs for inflated prices.

The authors also pointed to the marketplace economy as an obstacle to implementing their recommendations and preventing drug shortages. Drug manufacturers do not like to disclose manufacturing problems that lead to shortages, nor are competitive healthcare institutions accustomed to cooperating to share resources.

Nonetheless, the authors called for an exploration of “ways to facilitate inter-institutional and inter-state transfer of drugs, especially during shortages,” as well as the ethical obligation to patients inside vs outside a healthcare institution when there is a drug shortage.

“The reasons for drug shortages are complex, but we must not lose sight of the fact that, without access to these life-saving drugs, children and adults with cancer will almost certainly die,” Dr Unguru said. “It is untenable for this situation to continue any longer. We have a clear moral obligation to act to address this critical issue.”

Nurse hangs bags filled

with chemotherapy drugs

Credit: Bill Branson

A group of healthcare experts has created a “blueprint” for managing and preventing drug shortages.

They devised 6 recommendations for preempting shortages of pediatric oncology drugs, but the suggestions can be applied to other drugs as well.

Some of the recommendations would represent new norms for healthcare practice, such as sharing scarce drugs among healthcare institutions and not giving preferential access to patients participating in clinical trials.

The suggestions appear in a consensus statement published in Pediatrics.

“Although our recommendations were developed with pediatric oncology in mind, and serve as a blueprint for preventing children with cancer from lacking access to essential life-saving medications, we believe that they apply more broadly across medicine to include pediatrics and adult medicine in general,” said statement author Yoram Unguru, MD, of the Johns Hopkins Berman Institute of Bioethics in Baltimore, Maryland.

He and his coauthors developed the following recommendations:

1. Support national polices—and develop new measures—to prevent drug shortages
2. Use drug supplies efficiently to reduce the likelihood of shortages
3. Give equal priority to evidence-based uses of drugs, whether they occur within or outside clinical trials
4. Develop an improved clearinghouse for sharing drug shortage information
5. Explore the sharing of drug supplies among institutions
6. Develop strategies to engage stakeholders in the management of drug shortages.

For each recommendation, the authors included potential barriers to its implementation. A centralized information source of drug supply information, for instance, comes with the risk that such information will encourage hoarding of existing supplies. This includes “gray market” suppliers that sell scarce drugs for inflated prices.

The authors also pointed to the marketplace economy as an obstacle to implementing their recommendations and preventing drug shortages. Drug manufacturers do not like to disclose manufacturing problems that lead to shortages, nor are competitive healthcare institutions accustomed to cooperating to share resources.

Nonetheless, the authors called for an exploration of “ways to facilitate inter-institutional and inter-state transfer of drugs, especially during shortages,” as well as the ethical obligation to patients inside vs outside a healthcare institution when there is a drug shortage.

“The reasons for drug shortages are complex, but we must not lose sight of the fact that, without access to these life-saving drugs, children and adults with cancer will almost certainly die,” Dr Unguru said. “It is untenable for this situation to continue any longer. We have a clear moral obligation to act to address this critical issue.”

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the thrombopoietin receptor agonist eltrombopag (Promacta/Revolade) to treat patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is not approved in this setting anywhere in the world, and there are no approved therapies for SAA patients who are unresponsive to initial IST.

Of those patients who are unresponsive to initial IST, approximately 40% die from infection or bleeding within 5 years of their diagnosis.

Breakthrough therapy designation is the newest of the FDA’s programs aimed at accelerating the development and review of drugs for serious or life-threatening conditions. A drug receives the designation when preliminary clinical evidence suggests it may offer substantial improvement over available therapies on at least one clinically significant endpoint.

Eltrombopag was granted breakthrough designation based on results from an open-label, phase 2 study in 43 heavily pretreated SAA patients with an insufficient response to IST. Updated results of this trial were published in December (Desmond et al, Blood 2013).

Patients received varying doses of eltrombopag to improve blood counts. At 3 to 4 months of follow-up, the overall response rate was 40% (17/43), which included 1 tri-lineage and 5 bi-lineage responses.

Most of the 17 patients who remained on eltrombopag in an extension study continued to show improvement, but 3 lost their response. Ultimately, 7 patients had significant increases in neutrophil, red cell, and platelet counts.

Five patients who experienced robust near-normalization of blood counts discontinued the drug and maintained stable counts a median of 13 months after discontinuation (range, 1-15).

Eight patients, including 2 who responded, developed new cytogenetic abnormalities while on eltrombopag. But none have evolved to acute myeloid leukemia to date.

The only dose-limiting toxicity was reversible transaminitis. Two patients had reversible transaminitis related to treatment, and both required dose interruption.

There were no thrombotic events while patients were on treatment, but 1 responding patient developed deep-vein thrombosis 14 months after treatment discontinuation.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the thrombopoietin receptor agonist eltrombopag (Promacta/Revolade) to treat patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is not approved in this setting anywhere in the world, and there are no approved therapies for SAA patients who are unresponsive to initial IST.

Of those patients who are unresponsive to initial IST, approximately 40% die from infection or bleeding within 5 years of their diagnosis.

Breakthrough therapy designation is the newest of the FDA’s programs aimed at accelerating the development and review of drugs for serious or life-threatening conditions. A drug receives the designation when preliminary clinical evidence suggests it may offer substantial improvement over available therapies on at least one clinically significant endpoint.

Eltrombopag was granted breakthrough designation based on results from an open-label, phase 2 study in 43 heavily pretreated SAA patients with an insufficient response to IST. Updated results of this trial were published in December (Desmond et al, Blood 2013).

Patients received varying doses of eltrombopag to improve blood counts. At 3 to 4 months of follow-up, the overall response rate was 40% (17/43), which included 1 tri-lineage and 5 bi-lineage responses.

Most of the 17 patients who remained on eltrombopag in an extension study continued to show improvement, but 3 lost their response. Ultimately, 7 patients had significant increases in neutrophil, red cell, and platelet counts.

Five patients who experienced robust near-normalization of blood counts discontinued the drug and maintained stable counts a median of 13 months after discontinuation (range, 1-15).

Eight patients, including 2 who responded, developed new cytogenetic abnormalities while on eltrombopag. But none have evolved to acute myeloid leukemia to date.

The only dose-limiting toxicity was reversible transaminitis. Two patients had reversible transaminitis related to treatment, and both required dose interruption.

There were no thrombotic events while patients were on treatment, but 1 responding patient developed deep-vein thrombosis 14 months after treatment discontinuation.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the thrombopoietin receptor agonist eltrombopag (Promacta/Revolade) to treat patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is not approved in this setting anywhere in the world, and there are no approved therapies for SAA patients who are unresponsive to initial IST.

Of those patients who are unresponsive to initial IST, approximately 40% die from infection or bleeding within 5 years of their diagnosis.

Breakthrough therapy designation is the newest of the FDA’s programs aimed at accelerating the development and review of drugs for serious or life-threatening conditions. A drug receives the designation when preliminary clinical evidence suggests it may offer substantial improvement over available therapies on at least one clinically significant endpoint.

Eltrombopag was granted breakthrough designation based on results from an open-label, phase 2 study in 43 heavily pretreated SAA patients with an insufficient response to IST. Updated results of this trial were published in December (Desmond et al, Blood 2013).

Patients received varying doses of eltrombopag to improve blood counts. At 3 to 4 months of follow-up, the overall response rate was 40% (17/43), which included 1 tri-lineage and 5 bi-lineage responses.

Most of the 17 patients who remained on eltrombopag in an extension study continued to show improvement, but 3 lost their response. Ultimately, 7 patients had significant increases in neutrophil, red cell, and platelet counts.

Five patients who experienced robust near-normalization of blood counts discontinued the drug and maintained stable counts a median of 13 months after discontinuation (range, 1-15).

Eight patients, including 2 who responded, developed new cytogenetic abnormalities while on eltrombopag. But none have evolved to acute myeloid leukemia to date.

The only dose-limiting toxicity was reversible transaminitis. Two patients had reversible transaminitis related to treatment, and both required dose interruption.

There were no thrombotic events while patients were on treatment, but 1 responding patient developed deep-vein thrombosis 14 months after treatment discontinuation.

Prescription bottles

Credit: Steven Harbour

The phase 3 RESONATE study has been stopped early due to positive results in patients receiving ibrutinib.

In this trial, researchers compared the BTK inhibitor ibrutinib to the CD20-directed antibody ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The study has ended early because 2 key endpoints were met—namely, ibrutinib significantly improved progression-free and overall survival rates.

The RESONATE study enrolled 391 patients with relapsed or refractory CLL or SLL with measurable nodal disease who were not eligible for treatment with purine-analog-based therapy. Patients had received at least 1 prior therapy.

The researchers randomized patients to receive 420 mg of ibrutinib orally once daily or intravenous doses of ofatumumab over the course of 24 weeks until disease progression or unacceptable toxicity.

At the planned interim analysis, ibrutinib had significantly improved progression-free survival (the primary endpoint) and overall survival (a secondary endpoint).

And the safety profile of ibrutinib was acceptable, according to the companies developing the drug (Pharmacyclics, Inc. and Janssen Research and Development, LLC).

Based on these results, an independent data monitoring committee recommended that patients in the ofatumumab arm be given access to ibrutinib.

Pharmacyclics has informed the US Food and Drug Administration of this recommendation, and Janssen has informed the European Medicines Agency. Both companies are in talks with the health authorities to define the next regulatory steps.

Pharmacyclics has said detailed data from the RESONATE study will be presented at an upcoming oncology conference.

Ibrutinib was recently approved by the US Food and Drug Administration to treat mantle cell lymphoma.

Prescription bottles

Credit: Steven Harbour

The phase 3 RESONATE study has been stopped early due to positive results in patients receiving ibrutinib.

In this trial, researchers compared the BTK inhibitor ibrutinib to the CD20-directed antibody ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The study has ended early because 2 key endpoints were met—namely, ibrutinib significantly improved progression-free and overall survival rates.

The RESONATE study enrolled 391 patients with relapsed or refractory CLL or SLL with measurable nodal disease who were not eligible for treatment with purine-analog-based therapy. Patients had received at least 1 prior therapy.

The researchers randomized patients to receive 420 mg of ibrutinib orally once daily or intravenous doses of ofatumumab over the course of 24 weeks until disease progression or unacceptable toxicity.

At the planned interim analysis, ibrutinib had significantly improved progression-free survival (the primary endpoint) and overall survival (a secondary endpoint).

And the safety profile of ibrutinib was acceptable, according to the companies developing the drug (Pharmacyclics, Inc. and Janssen Research and Development, LLC).

Based on these results, an independent data monitoring committee recommended that patients in the ofatumumab arm be given access to ibrutinib.

Pharmacyclics has informed the US Food and Drug Administration of this recommendation, and Janssen has informed the European Medicines Agency. Both companies are in talks with the health authorities to define the next regulatory steps.

Pharmacyclics has said detailed data from the RESONATE study will be presented at an upcoming oncology conference.

Ibrutinib was recently approved by the US Food and Drug Administration to treat mantle cell lymphoma.

Prescription bottles

Credit: Steven Harbour

The phase 3 RESONATE study has been stopped early due to positive results in patients receiving ibrutinib.

In this trial, researchers compared the BTK inhibitor ibrutinib to the CD20-directed antibody ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The study has ended early because 2 key endpoints were met—namely, ibrutinib significantly improved progression-free and overall survival rates.

The RESONATE study enrolled 391 patients with relapsed or refractory CLL or SLL with measurable nodal disease who were not eligible for treatment with purine-analog-based therapy. Patients had received at least 1 prior therapy.

The researchers randomized patients to receive 420 mg of ibrutinib orally once daily or intravenous doses of ofatumumab over the course of 24 weeks until disease progression or unacceptable toxicity.

At the planned interim analysis, ibrutinib had significantly improved progression-free survival (the primary endpoint) and overall survival (a secondary endpoint).

And the safety profile of ibrutinib was acceptable, according to the companies developing the drug (Pharmacyclics, Inc. and Janssen Research and Development, LLC).

Based on these results, an independent data monitoring committee recommended that patients in the ofatumumab arm be given access to ibrutinib.

Pharmacyclics has informed the US Food and Drug Administration of this recommendation, and Janssen has informed the European Medicines Agency. Both companies are in talks with the health authorities to define the next regulatory steps.

Pharmacyclics has said detailed data from the RESONATE study will be presented at an upcoming oncology conference.

Ibrutinib was recently approved by the US Food and Drug Administration to treat mantle cell lymphoma.

Preparing medication for a trial

Credit: Esther Dyson

New research suggests that drugs are often rejected by the US Food and Drug Administration (FDA), not because they are unsafe or ineffective, but because there is not enough evidence to determine the drugs’ safety and efficacy.

Investigators reviewed about 300 drug applications and discovered a number of reasons why drugs were denied approval on the first try.

The FDA cited issues with dosing, trial populations, study endpoints, and inconsistencies in data as reasons for denial.

Leonard V. Sacks, MBBCh, of the FDA in Silver Springs, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The team reviewed marketing applications for all new molecular entities (NMEs; active ingredients never before marketed in the US) first submitted to the FDA between 2000 and 2012.

They used FDA correspondence and reviews to determine the scientific and regulatory reasons approvals were delayed or denied.

Of the 302 NME applications, 222 (73.5%) ultimately achieved marketing approval.

Half of all NMEs (151) were rejected on the first try, but 71 (47.0%) of these were approved following resubmission. The median time to approval was 435 days after the first action letter (range, 47-2374 days).

Drugs were denied approval for a number of reasons, including:

• Uncertainty about the optimal dose to maximize efficacy and minimize safety risks (15.9%)
• Inconsistent results for multiple predefined study endpoints (13.2%)
• Trial endpoints were unsatisfactory (13.2%)
• Inconsistencies in efficacy for portions of the study population (11.3%)
• The populations studied did not reflect the populations likely to use the drug (7.3%).

The investigators also found that the frequency of safety deficiencies was similar among never-approved drugs and drugs with delayed approval. However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals.

There were 48 drugs with initial efficacy concerns, and only 31.3% of these were eventually approved, compared to 61.5% of the 39 drugs with safety concerns alone.

There were 20 drugs (13.2%) that, despite showing superiority to placebo, were considered to have inadequate efficacy compared with the standard of care.

The investigators said that, taken together, these findings suggest there is room for improvement in new drug applications. But if drug sponsors increase communication with the FDA, particularly with regard to study design, they could reduce delays in drug approval.

Preparing medication for a trial

Credit: Esther Dyson

New research suggests that drugs are often rejected by the US Food and Drug Administration (FDA), not because they are unsafe or ineffective, but because there is not enough evidence to determine the drugs’ safety and efficacy.

Investigators reviewed about 300 drug applications and discovered a number of reasons why drugs were denied approval on the first try.

The FDA cited issues with dosing, trial populations, study endpoints, and inconsistencies in data as reasons for denial.

Leonard V. Sacks, MBBCh, of the FDA in Silver Springs, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The team reviewed marketing applications for all new molecular entities (NMEs; active ingredients never before marketed in the US) first submitted to the FDA between 2000 and 2012.

They used FDA correspondence and reviews to determine the scientific and regulatory reasons approvals were delayed or denied.

Of the 302 NME applications, 222 (73.5%) ultimately achieved marketing approval.

Half of all NMEs (151) were rejected on the first try, but 71 (47.0%) of these were approved following resubmission. The median time to approval was 435 days after the first action letter (range, 47-2374 days).

Drugs were denied approval for a number of reasons, including:

• Uncertainty about the optimal dose to maximize efficacy and minimize safety risks (15.9%)
• Inconsistent results for multiple predefined study endpoints (13.2%)
• Trial endpoints were unsatisfactory (13.2%)
• Inconsistencies in efficacy for portions of the study population (11.3%)
• The populations studied did not reflect the populations likely to use the drug (7.3%).

The investigators also found that the frequency of safety deficiencies was similar among never-approved drugs and drugs with delayed approval. However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals.

There were 48 drugs with initial efficacy concerns, and only 31.3% of these were eventually approved, compared to 61.5% of the 39 drugs with safety concerns alone.

There were 20 drugs (13.2%) that, despite showing superiority to placebo, were considered to have inadequate efficacy compared with the standard of care.

The investigators said that, taken together, these findings suggest there is room for improvement in new drug applications. But if drug sponsors increase communication with the FDA, particularly with regard to study design, they could reduce delays in drug approval.

Preparing medication for a trial

Credit: Esther Dyson

New research suggests that drugs are often rejected by the US Food and Drug Administration (FDA), not because they are unsafe or ineffective, but because there is not enough evidence to determine the drugs’ safety and efficacy.

Investigators reviewed about 300 drug applications and discovered a number of reasons why drugs were denied approval on the first try.

The FDA cited issues with dosing, trial populations, study endpoints, and inconsistencies in data as reasons for denial.

Leonard V. Sacks, MBBCh, of the FDA in Silver Springs, Maryland, and his colleagues conducted this research and reported the results in JAMA.

The team reviewed marketing applications for all new molecular entities (NMEs; active ingredients never before marketed in the US) first submitted to the FDA between 2000 and 2012.

They used FDA correspondence and reviews to determine the scientific and regulatory reasons approvals were delayed or denied.

Of the 302 NME applications, 222 (73.5%) ultimately achieved marketing approval.

Half of all NMEs (151) were rejected on the first try, but 71 (47.0%) of these were approved following resubmission. The median time to approval was 435 days after the first action letter (range, 47-2374 days).

Drugs were denied approval for a number of reasons, including:

• Uncertainty about the optimal dose to maximize efficacy and minimize safety risks (15.9%)
• Inconsistent results for multiple predefined study endpoints (13.2%)
• Trial endpoints were unsatisfactory (13.2%)
• Inconsistencies in efficacy for portions of the study population (11.3%)
• The populations studied did not reflect the populations likely to use the drug (7.3%).

The investigators also found that the frequency of safety deficiencies was similar among never-approved drugs and drugs with delayed approval. However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals.

There were 48 drugs with initial efficacy concerns, and only 31.3% of these were eventually approved, compared to 61.5% of the 39 drugs with safety concerns alone.

There were 20 drugs (13.2%) that, despite showing superiority to placebo, were considered to have inadequate efficacy compared with the standard of care.

The investigators said that, taken together, these findings suggest there is room for improvement in new drug applications. But if drug sponsors increase communication with the FDA, particularly with regard to study design, they could reduce delays in drug approval.

Bag of saline solution

The US Food and Drug Administration (FDA) has acknowledged the current shortage of intravenous (IV) solutions, particularly 0.9% sodium chloride injection (ie, saline), which is used as a priming solution and to provide patients with the necessary fluids for hydration.

The agency said the shortage has been triggered by a range of factors. A few manufacturers have cited increased demand as the cause, and the FDA said this could be a result of flu season.

The agency is now working with 3 manufacturers of IV solutions, Baxter Healthcare Corp., B. Braun Medical Inc., and Hospira Inc., to help preserve the supply of these products.

However, the FDA noted that addressing the shortage will depend on the demand of these products and supplier production. Millions of these IV solutions are used each week by healthcare professionals.

Visit the FDA’s drug shortage webpage for updates.

Bag of saline solution

The US Food and Drug Administration (FDA) has acknowledged the current shortage of intravenous (IV) solutions, particularly 0.9% sodium chloride injection (ie, saline), which is used as a priming solution and to provide patients with the necessary fluids for hydration.

The agency said the shortage has been triggered by a range of factors. A few manufacturers have cited increased demand as the cause, and the FDA said this could be a result of flu season.

The agency is now working with 3 manufacturers of IV solutions, Baxter Healthcare Corp., B. Braun Medical Inc., and Hospira Inc., to help preserve the supply of these products.

However, the FDA noted that addressing the shortage will depend on the demand of these products and supplier production. Millions of these IV solutions are used each week by healthcare professionals.

Visit the FDA’s drug shortage webpage for updates.

Bag of saline solution

The US Food and Drug Administration (FDA) has acknowledged the current shortage of intravenous (IV) solutions, particularly 0.9% sodium chloride injection (ie, saline), which is used as a priming solution and to provide patients with the necessary fluids for hydration.

The agency said the shortage has been triggered by a range of factors. A few manufacturers have cited increased demand as the cause, and the FDA said this could be a result of flu season.

The agency is now working with 3 manufacturers of IV solutions, Baxter Healthcare Corp., B. Braun Medical Inc., and Hospira Inc., to help preserve the supply of these products.

However, the FDA noted that addressing the shortage will depend on the demand of these products and supplier production. Millions of these IV solutions are used each week by healthcare professionals.

Visit the FDA’s drug shortage webpage for updates.