The highly selective oral spleen tyrosine kinase (SYK) inhibitor sovleplenib has demonstrated significant clinical benefit in patients with warm autoimmune haemolytic anaemia (wAIHA), with durable haemoglobin (Hb) response and a favourable safety profile, as shown in the phase III ESLIM-02 trial.
ESLIM-02 successfully met its primary endpoint, with the percentage of patients achieving durable response over 24 weeks of treatment being significantly higher with sovleplenib than placebo, at 66 percent vs 15 percent (p<0.001). [EHA 2026, abstract S301]
Co-investigator Dr Bing Han from Peking Union Medical College Hospital, Beijing, China, who presented the results at the annual EHA meeting, defined durable response as having an Hb level of ≥100 g/L with an increase of ≥20 g/L from baseline in three consecutive evaluations, separated by 7-day intervals, without the use of rescue therapy.
“The durable response benefit with sovleplenib was consistently observed across all subgroups,” including those defined by sex, age, baseline ECOG score and Hb values, wAIHA type, baseline concomitant therapy, and prior lines of therapy, Han said.
The subgroup of patients who were previously treated with rituximab also fared better with sovleplenib than placebo, with durable response rates of 69 percent and 16 percent, respectively (p=0.0022), she added.
In terms of safety, grade ≥3 treatment-emergent adverse events (TEAEs) occurred less frequently in the sovleplenib than the placebo arm (43.2 percent vs 58.7 percent), as did serious TEAEs (27.3 percent vs 50 percent). The most common TEAEs with sovleplenib were grade 1–2 elevations in AST and ALT. No TEAEs led to treatment discontinuation or death in the sovleplenib arm.
These findings indicate that “sovleplenib may represent a breakthrough therapy for patients with relapsed or refractory wAIHA,” according to Han. This is especially relevant, since there is an unmet need for effective and well-tolerated oral treatments, she added.
The ESLIM-02 trial
ESLIM-02 was conducted at 38 sites in China and included 90 adult patients with primary or secondary wAIHA and insufficient response to previous glucocorticoid treatment. Patients were required to have evidence of active haemolysis, positive direct antiglobulin test at baseline, and Hb levels of <100 g/L.
The patients were randomly assigned to receive treatment with sovleplenib 300 mg or placebo, administered orally once daily for 24 weeks. Patients who completed the 24-week double-blind treatment and subsequent 4-week safety follow-up and those who showed no response within 20 weeks of treatment were eligible to enter an open-label extension phase to receive sovleplenib.
Baseline patient characteristics were balanced between the sovleplenib and placebo arms. The average age was 51 years, with 80 percent female and 92.2 percent having primary wAIHA. More than a third of patients (38.9 percent) had prior treatment with rituximab, and 73.3 percent were receiving anti-wAIHA therapy at baseline, mostly glucocorticoid.
Results for the secondary endpoints also favoured sovleplenib over placebo. Overall response rate was 70 percent vs 22 percent (p<0.0001), and mean Hb increased by 26.6 vs 7 g/L over 24 weeks (p<0.0001).
Compared with placebo, sovleplenib was associated with faster onset of response (median, 3.1 vs 6.3 weeks) and prolonged durable response among responders (median duration, 14.1 vs 6.1 weeks).
The use of rescue therapy was substantially reduced with sovleplenib vs placebo (16 percent vs 54 percent; p=0.0001), and significantly fewer sovleplenib-treated patients received red blood cell transfusion (11 percent vs 43 percent; p=0.0009). Half of patients (50 percent) in the sovleplenib arm were able to taper or discontinue their concomitant medications as opposed to only 15 percent in the placebo arm (p=0.0033).
Over 24 weeks, FACIT-Fatigue scores decreased more with sovleplenib vs placebo, although the difference was not significant, Han noted.