Amgen Inc. (Nasdaq: AMGN) today announced the publication of results from the first open-label study to compare Nplate® (romiplostim) treatment to standard of care therapies (SOC) in non-splenectomized adult patients with chronic immune thrombocytopenia (ITP). The study results, which were published today in the New England Journal of Medicine (NEJM), show that both the incidence of treatment failure and need for splenectomy were reduced among the Nplate-treated patients. Data also showed that patients receiving SOC therapies required splenectomies earlier when compared with patients treated with Nplate. Additionally, patients in the Nplate group experienced increased platelet counts, higher platelet response rates, less bleeding, and fewer blood transfusions compared to patients in the SOC group. Adverse events associated with Nplate treatment were similar to those in previous studies, were generally mild or moderate in severity, and did not result in treatment discontinuation. Headache and fatigue were the most commonly reported adverse events.
"This is the first study to compare a variety of ITP treatments and demonstrated that Nplate not only maintained platelet counts more effectively than standard medical treatments, but also reduced overall treatment failure and splenectomies," said Dr. David J. Kuter, head of Hematology, Massachusetts General Hospital, Boston, and lead investigator and study author.
Chronic ITP is a serious autoimmune disorder characterized by low platelet counts in the blood (thrombocytopenia), which can lead to serious bleeding events.
Nplate Study Meets Co-Primary Endpoints
The year-long, open-label study had two co-primary endpoints: the incidence of treatment failure and the incidence of splenectomy.
- Incidence of Treatment Failure: The Nplate group had a significantly lower incidence of treatment failure. Results showed that 11 percent of Nplate patients (18/157) experienced treatment failure compared with 30 percent of SOC patients (23/77).
- Treatment failures were defined as patients having platelet counts less than or equal to 20,000 platelets per microliter for four consecutive weeks at the highest recommended dose and schedule, a major bleeding event, and/or a change in therapy due to intolerable side effects or bleeding symptoms. Patients who required a splenectomy due to intolerable side effects or bleeding symptoms were also counted as treatment failures.
- Incidence of Splenectomy: Nplate patients had a significantly lower incidence of splenectomy. Nine percent of Nplate patients (14/157) underwent splenectomy compared with 36 percent of patients (28/77) in the SOC group (p<0.001, odds ratio 0.17, 95 percent CI, 0.08-0.35).
Patients were enrolled into the study from North America, Europe, and Australia. Geographical regions had no effect on either incidence of treatment failure or splenectomy.
Nplate Study Meets Secondary Endpoints
Secondary endpoints of the study included time to splenectomy, platelet counts, and platelet response.
- Time to Splenectomy: Patients receiving Nplate experienced a significantly longer time to splenectomy than did SOC-treated patients (p<0.001).
- Platelet Count: The mean platelet count was higher in the Nplate group than the SOC group throughout the treatment period.
- Platelet Response: The platelet response rate (a weekly platelet count greater than 50,000 platelets per microliter) was 2.3 times greater in Nplate-treated patients than in SOC-treated patients (p<0.001).
- Between weeks two and 52, the percentage of patients with a platelet response ranged from 71 percent (108/152) to 92 percent (127/138) in the Nplate group (median platelet count: 108,000 to 176,000 platelets per microliter) and between 26 percent (16/62) and 51 percent (26/51) in the SOC group (median platelet count: 35,000 to 52,000 platelets per microliter).
"For many adult chronic ITP patients, the side effects of some SOC treatments, including splenectomies, are often more debilitating than the disease itself," said Professor Mathias Rummel, head of hematology at the Hospital of the Justus-Liebig University, Giessen, Germany. "Nplate may offer the potential for long-term effective treatment in patients who wish either to avoid or defer a splenectomy."
Nplate Study Shows Favorable Benefit: Risk Profile for Chronic ITP Patients
The safety profile was also comparable between patients receiving Nplate and those receiving SOC according to results from the study.
- Bleeding Events: There was a statistically significant lower exposure-adjusted incidence of overall bleeding events.
- Blood Transfusions: Forty-one blood transfusions were administered to 8 percent of Nplate patients (12/154) compared to 76 transfusions to 16 percent of SOC patients (12/75).
More than 90 percent of patients in both groups reported at least one adverse event during the treatment period. Headache and fatigue were the most commonly reported adverse events. Fewer patients in the Nplate group experienced a serious adverse event than the SOC group. Serious adverse events occurred in 23 percent (35/154) of patients who received Nplate and 37 percent (28/75) of patients who received SOC. Likewise, treatment-related serious adverse events occurred in fewer Nplate-treated patients (5 percent, 7/154) compared with 8 percent (6/75) of the SOC-treated patients. The most common serious adverse event was thrombocytopenia which occurred in 3 percent (5/154) of Nplate-treated patients and 12 percent (9/75) of SOC-treated patients. Two hematologic malignancies occurred in SOC-treated patients.