FDA starts priority review of BeOne's Venclexta rival

The FDA has started a priority review of BeOne Medicines' BCL2 inhibitor sonrotoclax in relapsed or refractory mantle cell lymphoma (MCL), setting up a decision on US approval next year.

Sonrotoclax is in the same class as AbbVie's Venclexta (venetoclax), which isn't approved to treat MCL, but has FDA clearance for various indications in chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML).

At the moment, Venclexta is the only BCL-2 drug on the US market, with global sales of $2.6 billion last year, although it has competition in China from Ascentage Pharma's lisaftoclax, which was approved for CLL and small lymphocytic lymphoma (SLL) earlier this year.

Focusing initially on MCL gives BeOne an opportunity to build a niche for sonrotoclax without direct competition, as it works towards expanding the label for sonrotoclax into new indications.

Along with MCL, the Chinese company is running several trials of the BCL2 inhibitor in other forms of non-Hodgkin lymphoma (NHL), CLL, AML, myelodysplastic syndrome, Waldenström's macroglobulinaemia, and multiple myeloma.

The FDA has also granted a breakthrough designation to sonrotoclax, which has been filed on the strength of the BGB-11417-201 study as a monotherapy for MCL patients previously treated with at least one line of anti-CD20 or BTK inhibitor therapies.

At the ASH haematology congress in Orlando, Florida, next month, BeOne is scheduled to present full data from the 125-subject study in patients previously treated with BTK inhibitors for the first time, having previously revealed that it met its primary overall response rate (ORR) endpoint.

According to the abstract for the study at ASH, sonrotoclax at a dose of 320 mg achieved a 53.4% ORR among 103 evaluable patients, with a complete response seen in 14.6% of them. The median duration of response was 15.8 months, with a median progression-free survival (PFS) of 6.5 months.

However, more than a third (37%) of patients treated with the drug at that dose had a serious treatment-emergent adverse event, most commonly pneumonia, which could be a consideration as the FDA carries out its review. According to BeOne, the treatment was well-tolerated, and the risks were manageable.

Marketing applications for sonrotoclax for MCL and CLL have also been filed in China, and submissions in the EU and other countries for MCL are also being prepared.

"Sonrotoclax is advancing with remarkable speed, from breakthrough therapy designation to priority review, all within a short window," said Lai Wang, BeOne's global head of R&D.

"That pace reflects both the strength of the data and the urgency of the need for patients with R/R MCL," he added. "With rapid, deep, and durable responses and a manageable safety profile, sonrotoclax is emerging as a potential best-in-class BCL2 inhibitor."