NMPA Accepts and Grants Priority Review to NDA for Sovleplenib in Primary Immune Thrombocytopenia

The China National Medical Products Administration (NMPA) has accepted the new drug application (NDA) for the novel, selective, oral spleen tyrosine kinase inhibitor sovleplenib for the treatment of adult patients with primary immune thrombocytopenia (ITP). The NDA was also granted priority review by the agency.¹

“We are pleased to have initiated the rolling submission of an NDA for sovleplenib in China as we look to bring this novel treatment to [patients with] ITP,” Weiguo Su, PhD, executive director, chief executive officer, and chief scientific officer of HUTCHMED, the manufacturer of sovleplenib, said in a news release. “Our submission includes data from the successful phase III ESLIM-01 trial in China which demonstrated a durable response rate of sovleplenib for patients. There is a significant need for new therapies in adult primary ITP which can significantly impair the quality of life for patients.”

The NDA is supported by findings from the phase 3 ESLIM-01 trial (NCT05029635), which enrolled 188 patients aged 18 to approximately 75 years with ITP and an ECOG performance status of 1 or less. Eligible patients also needed to have intolerance, insufficient response, or recurrence following at least 1 anti-ITP standard drug therapy, a history of response to previous ITP therapy, and have a duration of ITP of more than 6 months.²

Eligible patients were randomly assigned to receive oral sovleplenib 300 mg once daily for 24 weeks or oral matching placebo for 24 weeks. The primary end point was durable response rate; secondary end points included overall response rate (ORR) and incidence of adverse effects.

In August 2023, HUTCHMED announced that ESLIM-01 met its primary end point, with findings from the study displaying a clinically meaningful and a statistically significant increase in durable response rate among patients who received sovleplenib vs those treated with placebo. They noted that the ORR and safety secondary end points were also met. The full findings from ESLIM-01 will be submitted for presentation at an upcoming medical meeting, according to the manufacturer.³

In January 2022, breakthrough therapy designation was granted by the NMPA to sovleplenib for the indication that was evaluated in ESLIM-01. This designation was given because sovleplenib was deemed to be a new drug that could treat a serious condition for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies.¹

Findings from a phase 1/2 study (NCT03951623) of sovleplenib in patients with ITP provided the proof of concept and rationale for ESLIM-01. The double-blind, placebo-controlled study enrolled patients who were aged 18 to 75 years, had an ECOG performance score of 1 or less, had primary ITP for over 6 months, and did not respond or relapsed after prior frontline treatment or had poor response or postoperative relapse after a splenectomy.⁴

During the dose-escalation stage, patients received sovleplenib100 mg, 200 mg, or 300 mg once daily. In the dose-expansion portion, patients were randomly assigned 3:1 to receive sovleplenib at the recommended phase 2 dose (RP2D) or placebo, followed by a 16-week, open-label period with sovleplenib. The RP2D of sovleplenib was determined to be 300 mg once daily.

Forty-five patients were randomly assigned and received at least 1 dose of study drug during the 8-week double-blind period. Patients were treated with sovleplenib 100 mg (n = 6), 200 mg (n = 6), 300 mg (n = 16), and 400 mg (n = 6). Eleven patients received placebo.

Patients met the main efficacy end point at rates of 50% (95% CI, 12%-88%), 50% (95% CI, 12%-88%), 63% (95% CI, 35%-85%), and 33% (95% CI, 4%-78%), in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively, compared with 9% (95% CI, 0%-41%) in the placebo arm. Moreover, the ORR in the 300-mg arm was 80% (n = 16/20) among those who received continuous sovleplenib plus those who crossed over from placebo. The durable response rate was 31% among those who received continuous sovleplenib and 75% among those who crossed over from placebo (n = 4).

In terms of safety, 2 grade 2 or higher treatment-related treatment-emergent adverse effects (TEAEs) occurred in the sovleplenib groups during the 28-day safety evaluation period: hypertriglyceridemia and anemia. During weeks 0 through 8, the most common any-grade TEAEs included increased blood lactate dehydrogenase, hematuria, urinary tract infection, occult blood positivity and hyperuricemia. No TEAEs leading to death were reported.

Sovleplenib is also currently being examined for the treatment of patients with warm antibody autoimmune hemolytic anemia and indolent non-Hodgkin lymphoma in a phase 2/3 trial (NCT05535933) and a phase 1 study (NCT03779113), respectively.¹

References

1. HUTCHMED announces NDA acceptance in China for sovleplenib for the treatment of primary immune thrombocytopenia with priority review status. News release. HUTCHMED. January 10, 2024. Accessed January 11, 2024. https://www.globenewswire.com/news-release/2024/01/11/2807571/0/en/HUTCHMED-Announces-NDA-Acceptance-in-China-for-Sovleplenib-for-the-Treatment-of-Primary-Immune-Thrombocytopenia-with-Priority-Review-Status.html
2. Phase III study on HMPL-523 for treatment of ITP. ClinicalTrials.gov. Updated February 8, 2023. Accessed January 11, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05029635
3. HUTCHMED announces that the sovleplenib phase III ESLIM-01 study met its primary endpoint in primary immune thrombocytopenia in China. News release. HUTCHMED.