FDA cleared BeOne’s Beqalzi (sonrotoclax) for relapsed or refractory mantle cell lymphoma Wednesday, making it the first BCL-2 inhibitor specifically approved for MCL in the U.S.
AbbVie and Roche’s Venclexta has covered this indication only off-label. That changes now.
The accelerated approval covers patients who’ve failed at least two prior lines of therapy, including a BTK inhibitor. In a phase 1/2 trial, Beqalzi posted an overall response rate of 52% with a median duration of response of 15.8 months and a complete response rate of 16%.
The closest competitor, Eli Lilly’s Jaypirca, holds its own third-line MCL nod from early 2023, with a 50% ORR and a median duration of 8.3 months.
BeOne’s edge isn’t just efficacy. In preclinical assays, sonrotoclax showed 14 times the potency of Venclexta and six times the BCL-2 selectivity. The drug’s shorter half-life also simplifies tumor lysis syndrome monitoring: patients need a blood test before dosing and again 4-6 hours after, versus Venclexta’s 6-to-8 hour and 24-hour checks that sometimes require hospitalization.
MCL is the entry point. BeOne’s real target is chronic lymphocytic leukemia, where Venclexta dominates. Phase 1 CLL data showed 91% undetectable measurable residual disease at 48 weeks for frontline patients on Brukinsa plus Beqalzi, climbing to 98% at 96 weeks among 56 evaluable patients. AstraZeneca’s Amplify trial hit 45% uMRD with Calquence-Venclexta at about 56 weeks.
Confirmatory data from the Celestial-RRMCL trial is still required to convert the MCL approval to full status. MRD data from Celestial-TNCLL, expected later this year, could trigger a CLL regulatory filing.
— Sarah Chen