The FDA has approved a supplemental Biologics License Application for romiplostim, updating its label to include data demonstrating sustained platelet responses in adults with immune thrombocytopenia. Romiplostim is approved for the treatment of adult patients with newly diagnosed or persistent who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The FDA has approved a supplemental Biologics License Application (sBLA) for romiplostim (Nplate), updating its label to include data demonstrating sustained platelet responses in adults with immune thrombocytopenia (ITP). Romiplostim is approved for the treatment of adult patients with newly diagnosed or persistent (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.1
The approval is based on a phase II trial of 75 previously treated adult patients who are ≤6 months from their ITP diagnosis. Regarding the primary study endpoint, patients had a median length of platelet response (≥50 x 109/L) of 11 months (95% CI, 10-11) during the 12-month treatment period, and first platelet response occurred at a median time of 2.1 weeks (95% CI, 1.1-3.0) from treatment initiation. Seventy (93%) of 75 patients had ≥1 platelet response during the 1-year treatment period. The study also met its secondary endpoint, with 32% (n = 24) of patients achieving remission for ≥6 months.
"These new data are the first of their kind to prospectively examine treatment-free remission as an outcome for patients with ITP. Thirty-two percent of patients who received Nplate soon after an insufficient response to the first course of steroids maintained platelet response for at least six months without Nplate or any other ITP therapy," David M. Reese, MD, executive vice president of Research and Development at Amgen, the developer of romiplostim, said in a press release.
"This approval will provide patients the opportunity to receive Nplate earlier in the course of their disease, potentially reducing their need for prolonged steroid use. We are excited to make Nplate available to more patients with this rare blood disorder," added Reese.
The single-arm, open-label study included 75 adult patients diagnosed with ITP within ≤6 months who had an insufficient response (platelet count ≤30 x 109/L) to first-line therapy, including corticosteroids. Overall, prior treatments included corticosteroids, immunoglobulins and anti-D immunoglobulins, and rescue therapies were allowed. Patients enrolled on the study at median time of 2.2 months from ITP diagnosis. Romiplostim was administered subcutaneously through weekly injections over a 12-month treatment course. To maintain platelet counts (50 x 109/L to 200 x 109/L), individual dose adjustments were allowed.
Adverse events occurring in ≥5% of patients and at a rate ≥5% compared with placebo or standard of care included bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea, and oropharyngeal pain. The thrombocytosis rate was 2%.
Romiplostim also has an approved indication for pediatric patients. In December 2018, the FDA approved romiplostim for the treatment of pediatric patients aged ≥1 year with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The approval was based on 2 double-blind, placebo-controlled trials in this patient population. The first study (NCT01444417) randomized 62 patients with relapsed/refractory disease following ≥1 previous ITP treatment in a 2:1 ratio to either romiplostim (n = 42) or placebo (n = 20).2,3
Fifty-two percent (n = 22) of patients in the romiplostim arm achieved durable platelet response compared with 10% (n = 2) of the placebo arm (P <.05). According to the FDA, the trial design defined durable platelet response as “at least 6 weekly platelet counts ≥50 × 109/L during weeks 18 through 25 of treatment.” Seventy-one percent (n = 30) versus 20% (n = 4) of patients in the 2 arms, respectively, had overall platelet response (P <.05), which the FDA explained that the trial defined as “a durable or a transient platelet response.” In the romiplostim group, patients had platelet counts ≥50 x 109/L for a median of 12 weeks versus 1 week in the control arm (P <.05).
The second trial (NCT00515203) randomized 22 patients in a 3:1 ratio to romiplostim (n = 17) or placebo (n = 5). In the romiplostim group 88% (n = 15; 95% CI, 64%-99%) of patients during the treatment period reached a platelet count ≥50 x 109/L for 2 consecutive weeks and an increase in platelet count of ≥20 × 109/L above baseline for 2 consecutive weeks. Neither outcome measure was reached by any patient treated with placebo.
All-grade adverse events that occurred in ≥25% of patients were contusion, upper respiratory tract infection, and oropharyngeal pain.