Sovleplenib provided a statistically significant and clinically meaningful increase in durable response rate over placebo in adult patients with primary immune thrombocytopenia in China.
Sovleplenib (HMPL-523) provided a statistically significant and clinically meaningful increase in durable response rate over placebo in adult patients with primary immune thrombocytopenia (ITP) in China, meeting the primary end point of the phase 3 ESLIM-01 trial (NCT05029635). The agent also met key secondary end points, such as response rate and safety.1
Full findings are slated to be shared at an upcoming meeting, according to HUTCHMED Limited.
“Sovleplenib offers a potential new treatment for patients with chronic adult primary ITP who have received at least 1 prior therapy, a heterogenous disease that can persist for years and where there remains a significant need for new treatments” Michael Shi, MD, PhD, chief medical officer of HUTCHMED, stated in the press release. “We are very pleased to see the positive outcomes of the ESLIM-01 study and would like to thank the patients, their families, and the healthcare professionals who participated in this study and helped reach this achievement.”
The double-blind, placebo-controlled phase 3 trial enrolled patients who had an ITP diagnosis before randomization and a duration of disease that was greater than 6 months.2 Patients needed to be between 18 years and 75 years and an ECOG performance status of 0 to 1. Moreover, patients must have been intolerant to, experienced an insufficient response, or had recurrence following 1 or more standard anti-ITP agents. They needed to have a history of response to prior ITP therapy.
If patients had evidence of secondary causes of ITP, serious hemorrhage requiring immediate adjustment of platelet counts, symptomatic gastrointestinal hemorrhage within 6 months before screening, a known history of vital organ transplantation or hematopoietic stem cell or bone marrow transplantation, or they received a live vaccine in the 8 weeks before study start, they were excluded.
Other exclusion criteria included undergoing splenectomy in the 12 weeks before randomization, major surgery in 4 weeks before randomization, a history of malignant tumors or arterial/venous embolic disease, or intracranial hemorrhage in the 6 months before screening.
Study participants were randomly assigned to receive sovleplenib at a once-daily dose of 300 mg or placebo for 24 weeks.
Additional secondary end points of interest include pharmacokinetics and quality of life.2,3
“By meeting the primary and all the secondary end points in this study while demonstrating a good level of tolerability and once-daily oral dosing, I am optimistic that sovleplenib may be a potential choice to help patients [with] ITP,” Professor Ren-Chi Yang, MD, of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and co-leading principal investigator of the trial, stated in a press release.1
The rationale for ESLIM-01, which was first initiated in October 2021,3 was based on findings from a double-blind, placebo-controlled, phase 1/2 study (NCT03951623) of sovleplenib in patients with ITP.1,4 These patients were between the ages of 18 years and 75 years, had an ECOG performance status of 0 or 1, had primary ITP for longer than 6 months, and were not responsive to or relapsed following prior frontline treatment or experienced a poor response or relapse following splenectomy.4
For the dose-escalation portion of the trial, sovleplenib was evaluated at once-daily doses of 100 mg, 200 mg, and 300 mg. In the dose-expansion phase, patients were randomly assigned 3:1 to receive sovleplenib at the recommended phase 2 dose of 300 mg once daily or placebo followed by a 16-week, open-label period with sovleplenib.
Data showed that when the agent was administered at a once-daily dose of 300 mg, 40% of the 20 patients experienced a durable response to treatment; this was defined as having a platelet count of at least 50 x 109/L in 4 of 6 visits during week 14 through 24 of the study.1 Median time to response was 1.1 weeks in patients who received the agent at that dose level in the first 8 weeks of the study (n = 16).
Of the 41 patients who received treatment at all dose levels through week 24, 7% had treatment-emergent adverse effects (TEAEs) that required dose reductions or interruptions. No patients experienced TEAEs that resulted in discontinuation. Notably, no grade 3 or higher TEAEs were observed in more than 1 patient through week 24.1
Previously, in January 2022, sovleplenib was granted breakthrough therapy designation from the National Medical Products Administration of China.1 The agent is now under evaluation in patients with non-Hodgkin lymphoma as part of an ongoing phase 1 trial (NCT03779113).1,5