Rilzabrutinib provides durable platelet response for relapsed immune thrombocytopenia
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Key takeaways:
- Rilzabrutinib demonstrated rapid, stable and durable platelet responses among patients with relapsed immune thrombocytopenia.
- The study is ongoing to gain additional data in a narrower cohort of patients.
SAN DIEGO — Rilzabrutinib treatment led to rapid, stable and durable platelet responses among patients with relapsed immune thrombocytopenia, according to data presented at ASH Annual Meeting and Exposition.
Preliminary evidence had previously shown that treatment with the agent resulted in similar platelet responses and a favorable safety profile among patients with previously treat immune thrombocytopenia, researchers noted.
“It was reassuring that we still had a similar response rate,” Nichola Cooper, MD, professor of immune hematology at Imperial College London, told Healio. “This was patients that were even more refractory than in part A [of the study], so to continue to get a response rate in these patients was reassuring to see that it does indeed work, at least through part B of this study.”
Background and methodology
Researchers conducted a phase 1/phase 2 open-label study to evaluate the efficacy and safety of rilzabrutinib (Sanofi) — reversible Bruton tyrosine kinase inhibitor — among adults with relapsed immune thrombocytopenia.
They previously determined through part A of the study, published in The New England Journal of Medicine, that treatment with the investigativeagent resulted in rapid and durable platelet responses and a favorable safety profile among this patient population.
Part B of the study assessed the efficacy and safety of rilzabrutinib 400 mg given twice a day in patients with relapsed immune thrombocytopenia aged between 18 and 80 years with at least two baseline platelet counts higher than 30 × 109/L no less than 7 days apart in the 15 days before the first dose.
Safety and durable platelet response, defined as platelet counts 50 × 109/L on 8 or more of the last 12 weeks of rilzabrutinib without rescue medication, served as the primary endpoint.
Researchers allowed patients who completed 24 weeks of rilzabrutinib with platelet counts 50 × 109/L or 30 × 109/L and doubling from baseline in 4 or more of the last 8 weeks of treatment without rescue medication to continue in the long-term extension period of the study.
At baseline, 26 patients (median age, 57 years; 62% women) enrolled with a median baseline platelet count of 13 × 109/L (range, 2-24 × 109/L); patients also had a median duration of immune thrombocytopenia of 10.3 years (range, 0.7–48.2).
Results, next steps
Among the study population, nine patients (35%; 95% CI, 17-56) achieved the primary endpoint of durable platelet response, with approximately 25% of patients achieving platelet counts 50 × 109/L by day 15 of rilzabrutinib treatment.
Among 16 patients who achieved platelet counts 50 × 109/L, researchers noted a median time to first platelet count 50 × 109/L of 15 days (range, 7-134). Median platelet counts for both responders and nonresponders increased over time, according to researchers, exceeding the platelet count thresholds of 30 × 109/L at day 57 and 50 × 109/L at day 120.
Three patients (12%) received rescue medication during the main treatment period, whereas 15 patients (58%) completed 24 weeks of rilzabrutinib and 11 patients (42%) entered the long-term extension period.
During the main treatment period, researchers noted a median duration of treatment of 167 days (range, 7-169); 16 patients (62%) had one or more related treatment-emergent adverse events, including 35% diarrhea, 23% headache and 15% nausea.
Researchers labeled most adverse events as grade 1 or 2, with one grade 3 blood creatinine phosphokinase increase. Researchers reported no treatment-related grade 2 or higher bleeding/thrombotic events or infections, serious adverse events or deaths.
Part C of this study is ongoing, which plans to enroll 202 adult patients and 30 adolescents to assess efficacy and safety of oral rilzabrutinib in adults and adolescents with relapsed/refractory immune thrombocytopenia, according to Cooper.
“The critical thing is going to be the randomized, placebo-controlled trial to see if [rilzabrutinib] makes a difference or not compared with control,” Cooper told Healio. “These are patients with chronic refractory disease, so I would like to trial it in early-phase upfront to see if you can immune-modulate and get a higher percentage of patients into response. I think those are the two big unanswered questions.”
References:
Cooper N, et al. Abstract 685. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023, San Diego.
Kuter DJ, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2110297.
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Cooper N, et al. Abstract 685. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
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