The US Food and Drug Administration has granted accelerated approval to global biopharmaceutical company BeOne Medicines for its drug Beqalzi (sonrotoclax). The medicine is intended for patients with relapsed or refractory mantle cell lymphoma (MCL) – an aggressive lymphatic system cancer that returns after treatment or fails to respond to it. The drug is expected to reach the market in the second half of this year, a company spokesperson told Reuters.
In the United States, Beqalzi is the first approved drug in its class – a BCL‑2 inhibitor – for the specific treatment of mantle cell lymphoma. It targets the BCL‑2 protein, which helps cancer cells survive. The first BCL‑2 inhibitor on the market, Venclexta from AbbVie and Roche, is only used off‑label for this type of blood cancer.
But mantle cell lymphoma is only the first step for BeOne in its potential bid to reshape the entire BCL‑2 inhibitor market, currently dominated by Venclexta. The main battle will be in chronic lymphocytic leukaemia (CLL). That is where BeOne expects Beqalzi to show its advantage. In first‑line CLL trials, combining Beqalzi with Brukinsa (zanubrutinib) – BeOne’s own BTK inhibitor – achieved undetectable minimal residual disease in 98% of patients by week 96, compared with 45% for the Venclexta‑based regimen.
Although Beqalzi is the first BCL‑2 drug for MCL, it will also face competition from US‑based Eli Lilly and its non‑covalent BTK inhibitor Jaypirca, which was approved for third‑line therapy after BTK treatment as early as 2023.
In January, Beqalzi was already approved in China for relapsed or refractory mantle cell lymphoma, as well as for adults with a certain type of blood cancer who have received at least one prior line of therapy.
According to BeOne’s medical director Amit Agarwal, preclinical studies showed Beqalzi has 14‑fold higher activity and 6‑fold higher selectivity than Venclexta (venetoclax). Beqalzi’s shorter half‑life makes tumour lysis syndrome (TLS) monitoring easier: blood tests can be done before dosing and again after 4‑6 hours. Venclexta has a long half‑life, making TLS monitoring more complex and sometimes requiring hospitalisation.
In a trial involving heavily pre‑treated MCL patients receiving Beqalzi, 42 deaths were reported. However, the company attributes only one of these to infection. BeOne sees no major safety concerns with the drug and is “very encouraged” by its safety profile, which has now been tested in more than 2,000 patients. As part of the accelerated approval, the company is required to confirm Beqalzi’s benefit in the Phase III Celestial‑RRMCL trial, in which patients will receive either Brukinsa alone or a combination of Brukinsa and Beqalzi.