Romiplostim Receives FDA Approval for Pediatric ITP

December 14, 2018

Article

Romiplostim has been granted FDA approval for the treatment of pediatric patients aged ≥1 year with immune thrombocytopenia for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim (Nplate) has been granted FDA approval for the treatment of pediatric patients aged ≥1 year with immune thrombocytopenia (ITP) for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

In granting approval, the FDA considered data from 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).

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.

The FDA noted that all-grade adverse events (AEs) that occurred in ≥25% of patients were contusion, upper respiratory tract infection, and oropharyngeal pain.

Data were recently presented at the 2018 ASH Annual Meeting for an integrated analysis of data from 5 clinical trials that showed that most pediatric patients with ITP had rapid and durable platelet responses when treated with romiplostim.

Nearly 90% of 282 evaluable patients had platelet responses, which occurred after a median treatment duration of 6 weeks. Patients remained in response for a median of 76% of months during follow-up.

In general, romiplostim was well tolerated; 3% of patients discontinued treatment because of AEs.

The findings from 5 clinical trials of children with ITP treated with romiplostim included randomized and placebo-controlled trials, single-arm trials, open-label trials, and extension studies. The 282 children included in the analysis had a median age of 10, median ITP duration of 1.9 years, and median baseline platelet count of 14.3 x 10⁹/L.

The patients received a median of 2 prior ITP therapies before initiating romiplostim, and 46% of patients had 3 or more prior treatments. Treatment history most often included corticosteroids (88%), intravenous immunoglobulin (87%), anti-D antibody (23%), and rituximab (Rituxan; 21%).

Patients began romiplostim treatment at a dose of 1 µg/kg weekly, titrated to a maximum dose of 10 µg/kg weekly as needed to maintain a platelet count of 50,000 to 200,000/mL. The 282 patients had a median treatment duration of 65 weeks, including 62% of patients treated for at least 48 weeks, and the median dose was 6.6 µg/kg.

Overall, 89% of patients treated with romiplostim achieved a platelet response, defined as platelet count ≥50 x 10⁹/L. Patients maintained responses for a median of 11 months and for 75.6% of all months on treatment. When response was calculated from initial response (N = 232), patients maintained the response for a median of 14 months and for 92.3% of treatment months.

Among the 19 patients who had prolonged treatment-free responses, the median duration of the treatment-free intervals was 12 months.

A summary of the safety data showed that 24% of patients had a serious AE during romiplostim treatment, but no fatal AEs occurred. One patient had thrombocytosis associated with a platelet count of 1462 x 109/L at week 14 that persisted for 1 week. Another patient had elevated platelet counts on 10 different occasions during weeks 20 and 172, reaching a maximum of 872 x 109/L but without a thrombotic event.

The most commonly reported AEs in romiplostim-treated patients were headache (40%), epistaxis (39%), pyrexia (32%), and nasopharyngitis. Sixty-eight percent of patients had bleeding AEs, most of which were mild or moderate in severity. The most frequent bleeding AEs were epistaxis (39%), contusion (28%), petechiae (24%), and hematoma (15%). The most common serious AE was epistaxis (6%).

Data for 1 patient who had a bone marrow biopsy at investigator request showed an increase in modified Bauermeister bone marrow grade from 0 to 2 without any associated AE. In an ongoing open-label trial, bone marrow biopsies in 32 patients showed no collagen or bone marrow abnormalities.

References:

FDA approves romiplostim for pediatric patients with immune thrombocytopenia. FDA. Posted December 14, 2018. Accessed December 14, 2018. https://bit.ly/2EiYOnf?rel=0"
Tarantino MD, Despotovic J, Roy J, et al. Safety and efficacy of romiplostim in over 200 children with immune thrombocytopenia (ITP): results of an integrated database of 5 clinical trials. In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 2428