AbbVie and Johnson & Johnson’s Imbruvica just nabbed a three-month reprieve before a potential face-off against BeiGene’s rival med Brukinsa in chronic lymphocytic leukemia, a key battleground for BTK inhibitors.
The FDA has extended a decision date for Brukinsa’s application in chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), BeiGene said Monday. With another three months, the new target date is Jan. 20, 2023.
The agency needs the additional time to review new clinical data that BeiGene submitted from the phase 3 Alpine trial, which pitted Brukinsa against Imbruvica in previously treated CLL/SLL. Besides that, the Brukinsa application package also includes data from the Sequoia trial in newly diagnosed patients.
Brukinsa is approved in the U.S. for some small indications including mantle cell lymphoma, Waldenström’s macroglobulinemia and marginal zone lymphoma. But CLL/SLL represents the main blockbuster sales opportunity for BTK inhibitors like Brukinsa and Imbruvica.
For the Alpine study, BeiGene originally reported an interim analysis last year, showing that by an independent data review committee, Brukinsa narrowly missed statistical significance in terms of better tumor shrinkage than Imbruvica. By investigator calculation, which was Alpine’s primary endpoint, Brukinsa’s advantage had already met the statistical bar at interim.
Then in April, BeiGene trotted out updated data. This time, Brukinsa showed it was superior to Imbruvica also by independent review. Brukinsa triggered a response in 80.4% of patients with previously treated CLL/SLL, versus 72.9% for Imbruvica.
Since FDA’s high-profile rejection of Eli Lilly and Innovent Biologics’ PD-1 inhibitor Tyvyt, people have started to question the approvability of drugs with Chinese background. For Tyvyt, the FDA took issue with its phase 3 trial’s single-country patient enrollment in China, plus an outdated comparator arm.
Brukinsa’s Alpine and Sequoia studies don’t seem to have those problems. Both were global trials at sites across the U.S., Europe and Asia. For Alpine, Brukinsa is going head-to-head against market-leading Imbruvica. In Sequoia, the drug significantly cut the risk of disease progression or death by 58% over a combo of the chemotherapy bendamustine and Roche’s Rituxan in newly diagnosed CLL/SLL.
It’s worth noting that Sequoia started in November 2017, more than a year after Imbruvica got its FDA go-ahead in frontline CLL/SLL in March 2016. But during an interview with Fierce Pharma ahead of last year’s American Society of Hematology meeting, BeiGene’s then-chief medical officer of hematology, Jane Huang, M.D., said that Imbruvica wasn’t widely accepted as the standard of care at the time of Sequoia’s initiation partly because the drug was compared to a weak chemo called chlorambucil. She also pointed to Sequoia’s fast enrollment to prove that the bendamustine-Rituxan regimen was very much still in use despite Imbruvica’s frontline nod.
To compete with Imbruvica, BeiGene has also touted a safety advantage for Brukinsa. After median two years of follow-up, 4.6% Brukinsa takers experienced atrial fibrillation or flutter, versus 12% for Imbruvica.
The FDA extension is “more procedural in nature and likely an indication of eventual approval,” SVB Securities analysts wrote in a Monday note to clients. Even before the FDA decision, the National Comprehensive Cancer Network has already endorsed Brukinsa as a CLL/SLL treatment for both newly diagnosed and previously treated patients. Placement on NCCN guidelines is often used to support payer coverage decisions.
“We are confident that the data in our filing demonstrate Brukinsa’s potential in the treatment of CLL/SLL and are committed to bringing this important medicine to CLL/SLL patients in the U.S. as soon as possible following regulatory approval,” BeiGene CEO John Oyler said in a statement.