FDA approves romiplostim for thrombocytopenia

The agency developed a Risk Evaluation and Mitigation Strategy to achieve a positive benefit-risk ratio.

The FDA announced on Friday that romiplostim is approved for treatment in both splenectomized and non-splenectomized patients with chronic immune thrombocytopenic purpura.

The approval of romiplostim (Nplate, Amgen) was based on safety and efficacy data from two phase-3 trials published in a February issue of the Lancet.

Romiplostim is only approved in patients with chronic immune thrombocytopenic purpura and not for patients with myelodysplasia.

Safety concerns with romiplostim include fibrous bone marrow deposits and a possible drop in platelet counts after discontinuing romiplostim therapy. In addition, according to an FDA press release, in a study of 44 patients who had myelodysplasia and received romiplostim, four patients developed leukemia. Under the FDA Amendments Act of 2007, the FDA has developed a Risk Evaluation and Mitigation Strategy because of the risks associated with romiplostim. This strategy includes a patient medication guide and requires that all patients and prescribers enroll in a long-term safety tracking program.

Phase-3 data

In the two phase-3 trials, researchers from Massachusetts General Hospital and other sites across the United States and Europe evaluated the safety and efficacy of romiplostim in splenectomized (n=63) and non-splenectomized (n=62) patients with a mean of three platelet counts 30x10⁹/L or less. Patients were randomly assigned to weekly subcutaneous injections of romiplostim (splenectomized study, n=42; non-splenectomized study, n=41) or placebo (n=21) for 24 weeks.

Sixteen splenectomized and 25 non-splenectomized patients assigned to romiplostim had a durable platelet response, compared with zero splenectomized and one non-splenectomized patient assigned placebo.

The overall platelet response rate was superior for romiplostim in both splenectomized (79%) and non-splenectomized (88%) patients, compared with placebo (splenectomized, n=0 and non-splenectomized, 14%; P<.0001).

Patients assigned to romiplostim reached platelet counts of 50x10⁹/L or more for a longer period of time than those assigned to placebo (mean 13.8 weeks vs. 0.8 weeks).

Researchers reported a decrease or discontinuation of concurrent therapies, such as corticosteroids, in 87% of patients assigned to romiplostim, compared with 38% of placebo.

According to the researchers, mild to moderate adverse events were reported in 95% of patients assigned placebo and 100% of those assigned romiplostim. The most common adverse events in the romiplostim group were headache (35%), fatigue (33%) and epistaxis (32%).

Lancet. 2008;371:395-403.

This approval has been a while in coming and this is the first of several drugs like this that are going to be coming along. This rests on 2 bases: We now recognize that a lot of thrombocytopenia in chronic immune thrombocytopenic purpura is due to a lack of production and not the destruction of circulating platelets. And they’ve now found ways of stimulating the production by imitating thrombopoietin, and this is one of them. This is important because it treats patients who were formerly refractory to the treatments we had, which were often quite dangerous and difficult, and appears to treat them quite readily without serious side effects. Chronic immune thrombocytopenic purpura is a reasonably common problem, so this decision will affect a lot of people.

– Wendell Rosse, MD

HemOnc Today Editorial Board member