FDA Drops Safety Requirement For Nplate and Promacta
The U.S. Food and Drug Administration (FDA) has lifted requirements that anyone using, prescribing, or providing Nplate (Romiplostim) of Promacta (eltrombopag) enroll in a monitoring program, the agency said today.
"An FDA-initiated review of the current information has determined that while safety risks for both Nplate and Promacta still exist, certain restrictive requirements of the [risk evaluation and management strategy (REMS)] programs are no longer necessary to ensure that the benefits of the drugs outweigh their risks," the agency said in a press release.
Both Nplate and Promacta were both approved in August of 2008 to treat adult patients with chronic immune thrombocytopenia (ITP) who responded inadequately to corticosteroids, immunoglobulins, or splenectomy.
ITP is a rare blood disorder where patients are have a low number of platelets in their bloodstream, and can lead to serious and uncontrolled bleeding. The treatments stimulate the bone marrow to produce more platelets.
At the time of approval, experience with both drugs was limited, and safety concerns led to a decision to require a REMS program that included restricted distribution requirements for each drug to ensure that the benefits of the drugs outweighed their risks, the FDA said.
The clinical trials upon which the approvals were based consisted of small pools of participants and were relatively short in duration, the FDA said, but they identified several safety concerns for both drugs including evidence of bone marrow changes of collagen deposition (reticulin), higher risk for blood clots, increased risk of developing hematological malignancies resulting from the stimulation of bone marrow cells, worsening low blood platelet count, and the risk for bleeding shortly after discontinuing the drugs. Promacta may also cause liver injury.
FDA’s restricted distribution requirements required healthcare professionals, pharmacies, hospitals, specialty care facilities, and patients to enroll in a special access program to prescribe, dispense, or receive the drugs.
The goals of the REMS were to promote informed risk-benefit decisions before initiating treatment and while patients are on treatment to ensure appropriate use of the drugs and to establish the overall long-term safety and safe use of the drugs through periodic monitoring of all patients who receive them.
FDA has continued to monitor the safety of Nplate and Promacta, and to evaluate the REMS, the agency said, but in their review have suggested that the adverse events of concern with the drugs may be part of the natural history of ITP and other serious medical conditions in patients who use the drug, the agency said.
Furthermore because treated patients had underlying medical conditions that confounded with drug side effects, the data collected from the REMS programs were challenging to interpret, the FDA said.
On Tuesday, FDA decided to lift the old requirements that were part of the REMS program which monitored patient safety, and resolve that clinical trials, post-approval studies, and post-marketing adverse event reports should provide the necessary data to continue monitoring the long-term safety of Nplate and Promacta.
Doctors, hospitals, specialty care facilities, and patients are no longer required to be enrolled in the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program or the Promacta CARES Program to prescribe, dispense, or receive these products.
Doctors are no longer required to complete periodic safety forms for patients receiving Nplate or Promacta.
Pharmacies and pharmacists are no longer required to enroll in the Promacta CARES Program or verify prescriber and patient enrollment before dispensing Promacta.
Instead, the modified REMS programs will include a communication plan that will inform healthcare professionals about the changes to the REMS and the risks associated with each product.
Amgen also released a statement that states that its researchers, working with the FDA, "have determined that the safety information collected through the REMS, which is based on individual case safety reports, is inherently confounded by underlying medical conditions in the treated patient population and thus cannot be used to determine the precise role of Nplate in the development of the adverse events."