Pharmacy

Preparing drugs for a trial

Credit: Esther Dyson

After 2 deaths among patients receiving the BCL-2 inhibitor ABT-199, the company developing the drug has suspended enrollment in 5 trials and stopped dose-escalation of the drug.

The patients died of tumor lysis syndrome, a complication that likely stems from the drug’s potency, according to Tracy Sorrentino, a spokeswoman for the company, AbbVie.

Research has suggested the risk of tumor lysis syndrome might be eliminated by altering the dose of ABT-199, Sorrentino said.

But until that is confirmed, AbbVie has stopped dose-escalation in patients receiving ABT-199 and voluntarily suspended enrollment in phase 1 trials of the drug.

The trials are testing ABT-199, both alone and in combination, as a treatment for chronic lymphocytic leukemia, non-Hodgkin lymphoma, and small lymphocytic lymphoma.

Though enrollment has stopped for these trials, dosing of active patients in ABT-199 trials will continue. In addition, a study testing ABT-199 in women with systemic lupus erythematosus is still enrolling patients.

Sorrentino said AbbVie has “every expectation” the suspended enrollment is temporary, and refining the dose of ABT-199 may eliminate the problem. In fact, the company is still planning to begin phase 3 trials of the drug later this year.

Preparing drugs for a trial

Credit: Esther Dyson

After 2 deaths among patients receiving the BCL-2 inhibitor ABT-199, the company developing the drug has suspended enrollment in 5 trials and stopped dose-escalation of the drug.

The patients died of tumor lysis syndrome, a complication that likely stems from the drug’s potency, according to Tracy Sorrentino, a spokeswoman for the company, AbbVie.

Research has suggested the risk of tumor lysis syndrome might be eliminated by altering the dose of ABT-199, Sorrentino said.

But until that is confirmed, AbbVie has stopped dose-escalation in patients receiving ABT-199 and voluntarily suspended enrollment in phase 1 trials of the drug.

The trials are testing ABT-199, both alone and in combination, as a treatment for chronic lymphocytic leukemia, non-Hodgkin lymphoma, and small lymphocytic lymphoma.

Though enrollment has stopped for these trials, dosing of active patients in ABT-199 trials will continue. In addition, a study testing ABT-199 in women with systemic lupus erythematosus is still enrolling patients.

Sorrentino said AbbVie has “every expectation” the suspended enrollment is temporary, and refining the dose of ABT-199 may eliminate the problem. In fact, the company is still planning to begin phase 3 trials of the drug later this year.

Preparing drugs for a trial

Credit: Esther Dyson

After 2 deaths among patients receiving the BCL-2 inhibitor ABT-199, the company developing the drug has suspended enrollment in 5 trials and stopped dose-escalation of the drug.

The patients died of tumor lysis syndrome, a complication that likely stems from the drug’s potency, according to Tracy Sorrentino, a spokeswoman for the company, AbbVie.

Research has suggested the risk of tumor lysis syndrome might be eliminated by altering the dose of ABT-199, Sorrentino said.

But until that is confirmed, AbbVie has stopped dose-escalation in patients receiving ABT-199 and voluntarily suspended enrollment in phase 1 trials of the drug.

The trials are testing ABT-199, both alone and in combination, as a treatment for chronic lymphocytic leukemia, non-Hodgkin lymphoma, and small lymphocytic lymphoma.

Though enrollment has stopped for these trials, dosing of active patients in ABT-199 trials will continue. In addition, a study testing ABT-199 in women with systemic lupus erythematosus is still enrolling patients.

Sorrentino said AbbVie has “every expectation” the suspended enrollment is temporary, and refining the dose of ABT-199 may eliminate the problem. In fact, the company is still planning to begin phase 3 trials of the drug later this year.

Prescriptions
Credit: Steven Harbour

The US Food and Drug Administration (FDA) has granted accelerated approval for the immunomodulatory agent pomalidomide (Pomalyst) to treat patients with advanced multiple myeloma (MM).

Continued FDA approval for the drug may be contingent upon verification and description of clinical benefit in confirmatory trials.

Pomalidomide is intended for use in combination with dexamethasone to treat MM patients who have received at least 2 prior

therapies (including lenalidomide and a proteasome inhibitor) and who experienced progression within 60 days of their last treatment.

Pomalidomide has demonstrated some efficacy in this patient population in a number of studies.

In a study published in Blood last year (PG Richardson et al.), pomalidomide elicited responses in MM patients who were refractory to lenalidomide, bortezomib, or both drugs.

In a study presented at ASH 2011 (abstract 634), pomalidomide did not fare as well when given alone to patients with refractory MM. However, combining the drug with low-dose dexamethasone significantly improved responses.

A study presented at ASH 2012 (LBA-6) built upon those findings, showing that pomalidomide plus low-dose dexamethasone was superior to high-dose dexamethasone in MM patients who were refractory to lenalidomide and bortezomib.

Common side effects observed with pomalidomide include neutropenia, anemia, thrombocytopenia, fatigue, weakness, constipation, diarrhea, upper respiratory tract infections, back pain, and fever.

In addition, pomalidomide has been shown to cause venous thromboembolism, as well as severe, life-threatening birth defects in pregnant women. The drug carries a boxed warning alerting patients and healthcare professionals to both of these risks.

Because of the embryo-fetal risk, pomalidomide is available only through the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers must be certified with the program by enrolling and complying with the REMS requirements.

Patients must sign a patient-physician agreement form and comply with the REMS requirements. In particular, female patients who are not pregnant but can become pregnant must comply with the pregnancy testing and contraception requirements, and males must comply with contraception requirements.

Pharmacies must be certified with the Pomalyst REMS Program, must only dispense the drug to patients who are authorized to receive it, and must comply with REMS requirements. Both lenalidomide and thalidomide have similar REMS.

Pomalidomide is marketed by Celgene, which is based in Summit, New Jersey.

Prescriptions
Credit: Steven Harbour

The US Food and Drug Administration (FDA) has granted accelerated approval for the immunomodulatory agent pomalidomide (Pomalyst) to treat patients with advanced multiple myeloma (MM).

Continued FDA approval for the drug may be contingent upon verification and description of clinical benefit in confirmatory trials.

Pomalidomide is intended for use in combination with dexamethasone to treat MM patients who have received at least 2 prior

therapies (including lenalidomide and a proteasome inhibitor) and who experienced progression within 60 days of their last treatment.

Pomalidomide has demonstrated some efficacy in this patient population in a number of studies.

In a study published in Blood last year (PG Richardson et al.), pomalidomide elicited responses in MM patients who were refractory to lenalidomide, bortezomib, or both drugs.

In a study presented at ASH 2011 (abstract 634), pomalidomide did not fare as well when given alone to patients with refractory MM. However, combining the drug with low-dose dexamethasone significantly improved responses.

A study presented at ASH 2012 (LBA-6) built upon those findings, showing that pomalidomide plus low-dose dexamethasone was superior to high-dose dexamethasone in MM patients who were refractory to lenalidomide and bortezomib.

Common side effects observed with pomalidomide include neutropenia, anemia, thrombocytopenia, fatigue, weakness, constipation, diarrhea, upper respiratory tract infections, back pain, and fever.

In addition, pomalidomide has been shown to cause venous thromboembolism, as well as severe, life-threatening birth defects in pregnant women. The drug carries a boxed warning alerting patients and healthcare professionals to both of these risks.

Because of the embryo-fetal risk, pomalidomide is available only through the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers must be certified with the program by enrolling and complying with the REMS requirements.

Patients must sign a patient-physician agreement form and comply with the REMS requirements. In particular, female patients who are not pregnant but can become pregnant must comply with the pregnancy testing and contraception requirements, and males must comply with contraception requirements.

Pharmacies must be certified with the Pomalyst REMS Program, must only dispense the drug to patients who are authorized to receive it, and must comply with REMS requirements. Both lenalidomide and thalidomide have similar REMS.

Pomalidomide is marketed by Celgene, which is based in Summit, New Jersey.

Prescriptions
Credit: Steven Harbour

The US Food and Drug Administration (FDA) has granted accelerated approval for the immunomodulatory agent pomalidomide (Pomalyst) to treat patients with advanced multiple myeloma (MM).

Continued FDA approval for the drug may be contingent upon verification and description of clinical benefit in confirmatory trials.

Pomalidomide is intended for use in combination with dexamethasone to treat MM patients who have received at least 2 prior

therapies (including lenalidomide and a proteasome inhibitor) and who experienced progression within 60 days of their last treatment.

Pomalidomide has demonstrated some efficacy in this patient population in a number of studies.

In a study published in Blood last year (PG Richardson et al.), pomalidomide elicited responses in MM patients who were refractory to lenalidomide, bortezomib, or both drugs.

In a study presented at ASH 2011 (abstract 634), pomalidomide did not fare as well when given alone to patients with refractory MM. However, combining the drug with low-dose dexamethasone significantly improved responses.

A study presented at ASH 2012 (LBA-6) built upon those findings, showing that pomalidomide plus low-dose dexamethasone was superior to high-dose dexamethasone in MM patients who were refractory to lenalidomide and bortezomib.

Common side effects observed with pomalidomide include neutropenia, anemia, thrombocytopenia, fatigue, weakness, constipation, diarrhea, upper respiratory tract infections, back pain, and fever.

In addition, pomalidomide has been shown to cause venous thromboembolism, as well as severe, life-threatening birth defects in pregnant women. The drug carries a boxed warning alerting patients and healthcare professionals to both of these risks.

Because of the embryo-fetal risk, pomalidomide is available only through the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers must be certified with the program by enrolling and complying with the REMS requirements.

Patients must sign a patient-physician agreement form and comply with the REMS requirements. In particular, female patients who are not pregnant but can become pregnant must comply with the pregnancy testing and contraception requirements, and males must comply with contraception requirements.

Pharmacies must be certified with the Pomalyst REMS Program, must only dispense the drug to patients who are authorized to receive it, and must comply with REMS requirements. Both lenalidomide and thalidomide have similar REMS.

Pomalidomide is marketed by Celgene, which is based in Summit, New Jersey.

The FDA generally approves drugs faster than its Canadian and European counterparts, according to a study published in this week’s edition of NEJM.

The researchers say these results refute criticisms that the drug approval process in the US is slow and that agencies in other countries tend to approve new therapies first.

“The perception that the FDA is too slow implies that sick patients are waiting unnecessarily for regulators to complete their review of new drug applications,” said lead study author Nicholas Downing, a medical student at Yale University.

He and his colleagues decided to conduct this study because there have been no recent comparisons of the FDA’s review speed with that of agencies in other countries.

So the researchers reviewed drug approval decisions made by the FDA, Health Canada, and the European Medicines Agency (EMA) between 2001 and 2010. The team said they chose Health Canada and the EMA as comparisons because these agencies face similar pressures to approve new drugs quickly while ensuring they don’t put patients at risk.

The investigators studied each regulator’s database of drug approvals to identify novel therapeutics, as well as the timing of key regulatory events. They then calculated each agency’s review speed.

The median total time to review a new drug application was 322 days at the FDA, 366 days at the EMA, and 393 days at Health Canada.

“Among the subsample of drugs approved for all 3 regulators, the FDA’s reviews were over 3 months faster than those of the EMA or Health Canada,” Downing said. “The total review time at the FDA was faster than EMA, despite the FDA’s far higher proportion of applications requiring multiple regulatory reviews.”

The researchers also found that, during the review period, the FDA approved 225 new drugs, the EMA approved 186, and Health Canada approved 99. Additionally, of the therapies that have been approved by all 3 agencies, most drugs were first approved in the US.

“[W]e found that 64% of medicines approved in both the US and in Europe were approved for US patients first,” Downing said. “And 86% of medicines approved in both the US and Canada were also approved first in the US.”

Downing and his colleagues noted that this study has 2 key limitations. First, the researchers didn’t account for drugs that were ultimately rejected, as the regulatory agencies don’t release review times for drugs that are never approved. However, the team also pointed out that the FDA approves more than 80% of its applications, so the exclusion may not have made much of an impact.

Secondly, the study included only new molecular entities and original biologic agents. In order to get a more accurate reading on the regulatory review process, research would need to evaluate the review of generic drugs, reformulated drugs, combination therapies, and medical devices.

The FDA generally approves drugs faster than its Canadian and European counterparts, according to a study published in this week’s edition of NEJM.

The researchers say these results refute criticisms that the drug approval process in the US is slow and that agencies in other countries tend to approve new therapies first.

“The perception that the FDA is too slow implies that sick patients are waiting unnecessarily for regulators to complete their review of new drug applications,” said lead study author Nicholas Downing, a medical student at Yale University.

He and his colleagues decided to conduct this study because there have been no recent comparisons of the FDA’s review speed with that of agencies in other countries.

So the researchers reviewed drug approval decisions made by the FDA, Health Canada, and the European Medicines Agency (EMA) between 2001 and 2010. The team said they chose Health Canada and the EMA as comparisons because these agencies face similar pressures to approve new drugs quickly while ensuring they don’t put patients at risk.

The investigators studied each regulator’s database of drug approvals to identify novel therapeutics, as well as the timing of key regulatory events. They then calculated each agency’s review speed.

The median total time to review a new drug application was 322 days at the FDA, 366 days at the EMA, and 393 days at Health Canada.

“Among the subsample of drugs approved for all 3 regulators, the FDA’s reviews were over 3 months faster than those of the EMA or Health Canada,” Downing said. “The total review time at the FDA was faster than EMA, despite the FDA’s far higher proportion of applications requiring multiple regulatory reviews.”

The researchers also found that, during the review period, the FDA approved 225 new drugs, the EMA approved 186, and Health Canada approved 99. Additionally, of the therapies that have been approved by all 3 agencies, most drugs were first approved in the US.

“[W]e found that 64% of medicines approved in both the US and in Europe were approved for US patients first,” Downing said. “And 86% of medicines approved in both the US and Canada were also approved first in the US.”

Downing and his colleagues noted that this study has 2 key limitations. First, the researchers didn’t account for drugs that were ultimately rejected, as the regulatory agencies don’t release review times for drugs that are never approved. However, the team also pointed out that the FDA approves more than 80% of its applications, so the exclusion may not have made much of an impact.

Secondly, the study included only new molecular entities and original biologic agents. In order to get a more accurate reading on the regulatory review process, research would need to evaluate the review of generic drugs, reformulated drugs, combination therapies, and medical devices.

The FDA generally approves drugs faster than its Canadian and European counterparts, according to a study published in this week’s edition of NEJM.

The researchers say these results refute criticisms that the drug approval process in the US is slow and that agencies in other countries tend to approve new therapies first.

“The perception that the FDA is too slow implies that sick patients are waiting unnecessarily for regulators to complete their review of new drug applications,” said lead study author Nicholas Downing, a medical student at Yale University.

He and his colleagues decided to conduct this study because there have been no recent comparisons of the FDA’s review speed with that of agencies in other countries.

So the researchers reviewed drug approval decisions made by the FDA, Health Canada, and the European Medicines Agency (EMA) between 2001 and 2010. The team said they chose Health Canada and the EMA as comparisons because these agencies face similar pressures to approve new drugs quickly while ensuring they don’t put patients at risk.

The investigators studied each regulator’s database of drug approvals to identify novel therapeutics, as well as the timing of key regulatory events. They then calculated each agency’s review speed.

The median total time to review a new drug application was 322 days at the FDA, 366 days at the EMA, and 393 days at Health Canada.

“Among the subsample of drugs approved for all 3 regulators, the FDA’s reviews were over 3 months faster than those of the EMA or Health Canada,” Downing said. “The total review time at the FDA was faster than EMA, despite the FDA’s far higher proportion of applications requiring multiple regulatory reviews.”

The researchers also found that, during the review period, the FDA approved 225 new drugs, the EMA approved 186, and Health Canada approved 99. Additionally, of the therapies that have been approved by all 3 agencies, most drugs were first approved in the US.

“[W]e found that 64% of medicines approved in both the US and in Europe were approved for US patients first,” Downing said. “And 86% of medicines approved in both the US and Canada were also approved first in the US.”

Downing and his colleagues noted that this study has 2 key limitations. First, the researchers didn’t account for drugs that were ultimately rejected, as the regulatory agencies don’t release review times for drugs that are never approved. However, the team also pointed out that the FDA approves more than 80% of its applications, so the exclusion may not have made much of an impact.

Secondly, the study included only new molecular entities and original biologic agents. In order to get a more accurate reading on the regulatory review process, research would need to evaluate the review of generic drugs, reformulated drugs, combination therapies, and medical devices.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.