FDA Drops Restrictions for Thrombocytopenia Treatments

The Food and Drug Administration’s decision to downsize the Risk Evaluation and Mitigation Strategies for romiplostim and eltrombopag shows that the agency is continuing its trend of moving away from an aggressive application of the drug safety tools, particularly when additional information comes in through the assessment process.

The FDA announced Dec. 6 that it would no longer require health care professionals, hospitals, specialty care facilities, and patients to enroll in a restricted access program in order to prescribe or receive the thrombocytopenia treatments and that physicians will no longer be required to complete periodic safety forms for patients receiving the therapies.

Pharmacies also will no longer be required to enroll in the programs or verify prescriber and patient enrollment before dispensing eltrombopag (Promacta, GlaxoSmithKline), an oral therapy covered under Medicare Part D.

Drug maker Amgen is hoping that the revision to the Risk Evaluation and Mitigation Strategies (REMS) will help it get romiplostim (marketed as Nplate) off the Centers for Medicare and Medicaid Services list for a potential Medicare National Coverage Determination.

Modified REMS for the two drugs will now include a communications plan to inform health care professionals about changes to the risk management program and to reinforce safety risks associated with each product. The patient Medication Guide will be separated from the REMS, but continue to be part of labeling.

The changes came after additional information was submitted under the REMS assessment process. The FDA has already shown a willingness to modify the programs based on incoming information, such as for golimumab and sacrosidase. And the agency has modified its approach to Medication Guides and REMS, no longer requiring all MedGuides to be linked to the REMS.

REMS Review Led to Labeling Changes

The FDA approved both romiplostim and eltrombopag in 2008 to treat adults with chronic immune thrombocytopenia – a rare autoimmune-mediated blood disorder that results in a low platelet count and associated bleeding risk – who have not responded to corticosteroids, immunoglobulins or splenectomy. The drugs work by stimulating bone marrow to produce needed platelets, but the process is not without risk.

Since the approvals, the FDA has monitored bone marrow changes of collagen deposition (reticulin), risk of blood clots, risk of developing blood-related cancers resulting from bone marrow stimulation, and the increased risk of low blood platelet count or bleeding after discontinuation. Eltrombopag also carries a boxed warning concerning the risk of liver toxicity. In addition to the reports required by the REMS, the drugs’ manufacturers have submitted data from ongoing clinical trials to clarify the safety profiles of their therapies.

The agency based the new labeling on both long-term safety data submitted from those trials and a determination that causality of adverse events in the individual case safety reports collected through the REMS was difficult to assign when the side effects of the therapies were mixed with the underlying medical conditions of the patients.

While REMS continue to be "vital tools" for FDA, "the agency remains committed to exercising a flexible and responsible regulatory approach" to ensure the programs are effective and efficient and not "resulting in an unnecessary burden on health care professionals and patients," Center for Drug Evaluation and Research Director Janet Woodcock said in a statement.

Will Labeling Changes Soften CMS’s Position on Romiplostim?

CMS put romiplostim on its list of potential National Coverage Determination topics even before it was approved, expressing safety concerns regarding thrombopoiesis-stimulating agents because they lacked long-term safety data, an overhang that has irked Amgen. The company has argued that romiplostim’s comprehensive REMS program – the first to include a mandatory patient registry – and long list of postmarketing safety studies precluded the need for CMS to consider coverage restrictions.

It appears that the most recent REMS assessment, based on completed phase IV clinical studies, was how Amgen was able to convince the government to drop some of the most arduous restrictions.

"The Pink Sheet" and this news organization are owned by Elsevier.

The Food and Drug Administration’s decision to downsize the Risk Evaluation and Mitigation Strategies for romiplostim and eltrombopag shows that the agency is continuing its trend of moving away from an aggressive application of the drug safety tools, particularly when additional information comes in through the assessment process.

The FDA announced Dec. 6 that it would no longer require health care professionals, hospitals, specialty care facilities, and patients to enroll in a restricted access program in order to prescribe or receive the thrombocytopenia treatments and that physicians will no longer be required to complete periodic safety forms for patients receiving the therapies.

Pharmacies also will no longer be required to enroll in the programs or verify prescriber and patient enrollment before dispensing eltrombopag (Promacta, GlaxoSmithKline), an oral therapy covered under Medicare Part D.

Drug maker Amgen is hoping that the revision to the Risk Evaluation and Mitigation Strategies (REMS) will help it get romiplostim (marketed as Nplate) off the Centers for Medicare and Medicaid Services list for a potential Medicare National Coverage Determination.

Modified REMS for the two drugs will now include a communications plan to inform health care professionals about changes to the risk management program and to reinforce safety risks associated with each product. The patient Medication Guide will be separated from the REMS, but continue to be part of labeling.

The changes came after additional information was submitted under the REMS assessment process. The FDA has already shown a willingness to modify the programs based on incoming information, such as for golimumab and sacrosidase. And the agency has modified its approach to Medication Guides and REMS, no longer requiring all MedGuides to be linked to the REMS.

REMS Review Led to Labeling Changes

The FDA approved both romiplostim and eltrombopag in 2008 to treat adults with chronic immune thrombocytopenia – a rare autoimmune-mediated blood disorder that results in a low platelet count and associated bleeding risk – who have not responded to corticosteroids, immunoglobulins or splenectomy. The drugs work by stimulating bone marrow to produce needed platelets, but the process is not without risk.

Since the approvals, the FDA has monitored bone marrow changes of collagen deposition (reticulin), risk of blood clots, risk of developing blood-related cancers resulting from bone marrow stimulation, and the increased risk of low blood platelet count or bleeding after discontinuation. Eltrombopag also carries a boxed warning concerning the risk of liver toxicity. In addition to the reports required by the REMS, the drugs’ manufacturers have submitted data from ongoing clinical trials to clarify the safety profiles of their therapies.

The agency based the new labeling on both long-term safety data submitted from those trials and a determination that causality of adverse events in the individual case safety reports collected through the REMS was difficult to assign when the side effects of the therapies were mixed with the underlying medical conditions of the patients.

While REMS continue to be "vital tools" for FDA, "the agency remains committed to exercising a flexible and responsible regulatory approach" to ensure the programs are effective and efficient and not "resulting in an unnecessary burden on health care professionals and patients," Center for Drug Evaluation and Research Director Janet Woodcock said in a statement.

Will Labeling Changes Soften CMS’s Position on Romiplostim?

CMS put romiplostim on its list of potential National Coverage Determination topics even before it was approved, expressing safety concerns regarding thrombopoiesis-stimulating agents because they lacked long-term safety data, an overhang that has irked Amgen. The company has argued that romiplostim’s comprehensive REMS program – the first to include a mandatory patient registry – and long list of postmarketing safety studies precluded the need for CMS to consider coverage restrictions.

It appears that the most recent REMS assessment, based on completed phase IV clinical studies, was how Amgen was able to convince the government to drop some of the most arduous restrictions.

"The Pink Sheet" and this news organization are owned by Elsevier.

The Food and Drug Administration’s decision to downsize the Risk Evaluation and Mitigation Strategies for romiplostim and eltrombopag shows that the agency is continuing its trend of moving away from an aggressive application of the drug safety tools, particularly when additional information comes in through the assessment process.

The FDA announced Dec. 6 that it would no longer require health care professionals, hospitals, specialty care facilities, and patients to enroll in a restricted access program in order to prescribe or receive the thrombocytopenia treatments and that physicians will no longer be required to complete periodic safety forms for patients receiving the therapies.

Pharmacies also will no longer be required to enroll in the programs or verify prescriber and patient enrollment before dispensing eltrombopag (Promacta, GlaxoSmithKline), an oral therapy covered under Medicare Part D.

Drug maker Amgen is hoping that the revision to the Risk Evaluation and Mitigation Strategies (REMS) will help it get romiplostim (marketed as Nplate) off the Centers for Medicare and Medicaid Services list for a potential Medicare National Coverage Determination.

Modified REMS for the two drugs will now include a communications plan to inform health care professionals about changes to the risk management program and to reinforce safety risks associated with each product. The patient Medication Guide will be separated from the REMS, but continue to be part of labeling.

The changes came after additional information was submitted under the REMS assessment process. The FDA has already shown a willingness to modify the programs based on incoming information, such as for golimumab and sacrosidase. And the agency has modified its approach to Medication Guides and REMS, no longer requiring all MedGuides to be linked to the REMS.

REMS Review Led to Labeling Changes

The FDA approved both romiplostim and eltrombopag in 2008 to treat adults with chronic immune thrombocytopenia – a rare autoimmune-mediated blood disorder that results in a low platelet count and associated bleeding risk – who have not responded to corticosteroids, immunoglobulins or splenectomy. The drugs work by stimulating bone marrow to produce needed platelets, but the process is not without risk.

Since the approvals, the FDA has monitored bone marrow changes of collagen deposition (reticulin), risk of blood clots, risk of developing blood-related cancers resulting from bone marrow stimulation, and the increased risk of low blood platelet count or bleeding after discontinuation. Eltrombopag also carries a boxed warning concerning the risk of liver toxicity. In addition to the reports required by the REMS, the drugs’ manufacturers have submitted data from ongoing clinical trials to clarify the safety profiles of their therapies.

The agency based the new labeling on both long-term safety data submitted from those trials and a determination that causality of adverse events in the individual case safety reports collected through the REMS was difficult to assign when the side effects of the therapies were mixed with the underlying medical conditions of the patients.

While REMS continue to be "vital tools" for FDA, "the agency remains committed to exercising a flexible and responsible regulatory approach" to ensure the programs are effective and efficient and not "resulting in an unnecessary burden on health care professionals and patients," Center for Drug Evaluation and Research Director Janet Woodcock said in a statement.

Will Labeling Changes Soften CMS’s Position on Romiplostim?

CMS put romiplostim on its list of potential National Coverage Determination topics even before it was approved, expressing safety concerns regarding thrombopoiesis-stimulating agents because they lacked long-term safety data, an overhang that has irked Amgen. The company has argued that romiplostim’s comprehensive REMS program – the first to include a mandatory patient registry – and long list of postmarketing safety studies precluded the need for CMS to consider coverage restrictions.

It appears that the most recent REMS assessment, based on completed phase IV clinical studies, was how Amgen was able to convince the government to drop some of the most arduous restrictions.

"The Pink Sheet" and this news organization are owned by Elsevier.