The FDA has approved romiplostim (Nplate) 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.
The approval is 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).1
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
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.
"Children with ITP are at risk for serious bleeding events and spontaneous bruising due to low platelet counts, which can be worrying for these young patients and their parents. Currently, these patients have a limited number of treatment options, especially for those with refractory disease," Michael D. Tarantino, MD, president of the Bleeding and Clotting Disorders Institute and professor of Pediatrics and Medicine, University of Illinois College of Medicine-Peoria, said in a statement. "Today's approval of Nplate offers new hope to the pediatric ITP community as it provides children with a new treatment option that may help to maintain safe platelet counts."
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.2
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
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.
- 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