- BeiGene missed a chance to show its new cancer drug could improve on AbbVie and Johnson & Johnson's top-selling Imbruvica in a rare type of lymphoma, announcing Monday a late-stage study comparing the two drugs failed to show a statistically significant advantage for the Chinese biotech's Brukinsa.
- The trial, called ASPEN and testing Brukinsa as a treatment for Waldenstrom macroglobulinemia, is one of two Phase 3 studies aimed at proving the drug's superiority over Imbruvica in advanced blood cancers. Brunkinsa's safety profile looks better than Imbruvica's, with fewer cases of irregular heartbeat and patients discontinuing because of adverse events.
- BeiGene did not say if it plans to submit the ASPEN data for regulatory approval, saying only that it will discuss the results with the Food and Drug Administration and the European Medicines Agency.
Head-to-head trials have high risks, but if successful can deliver bigger rewards. For Brukinsa (zanubrutinib), its status as a third-to-market drug means a strong commercial case is just as important to its success as a scientific one, so BeiGene decided to try to show it was better than Imbruvica.
"We had a conviction that we could have a best-in-class molecule," Jane Huang, hematology chief medical officer at BeiGene, said in an interview with BioPharma Dive at the recent American Society of Hematology meeting. "We wouldn't have invested in such an experiment if we didn't think it could be positive."
In ASPEN, Brukinsa fell short. The trial was designed to compare the two drugs based on shrinking of lymph nodes and reduction of an abnormal blood protein. In the trial 28% of Brukinsa patients and 19% of Imbruvica patients saw their lymph nodes return to normal and the blood protein levels drop 90%, called "very good partial response," or VGPR.
Although it was numerically higher, Brukinsa's VGPR rate did not meet a statistical standard for proving superiority.
ASPEN is the only global trial of Brukinsa in Waldenstrom's macroglobulinemia, with a China-only trial in relapsed disease underway. Thus it is not clear whether the FDA would consider data from either of those trials, given that one statistically was a failure and the other is in a non-US patient population.
One factor the FDA could take into account is safety. A particular concern with Imbruvica is occurrences of atrial fibrillation, and in this trial 15% of Imbruvica patients experienced this compared with just 2% of Brukinsa patients.
And although the numbers were small, nine patients on Imbruvica dropped out to four on Brukinsa in the trial, which had an average follow-up of 19 months. In real-world use, around 40% of Imbruvica patients stop treatment, often due to diarrhea, a side effect which occurred less frequently with Brukinsa, Piper Jaffray analyst Tyler Van Buren wrote in a Dec. 16 note to clients.
Nonetheless, Imbruvica remains the drug to beat in this drug class, called Bruton's tyrosine kinase inhibitors, wrote analysts covering AbbVie and J&J.
"Had this trial met the primary endpoint, revisiting our Imbruvica estimates may have been necessary, but for now we remain comfortable with our Imbruvica revenue estimates," wrote Christopher Raymond, who covers AbbVie for Piper Jaffray. He forecasts AbbVie's revenue from Imbruvica rising to $7.3 billion in 2023 from $3.6 billion in 2018.
BeiGene's other head-to-head trial against Imbruvica is in relapsed chronic lymphocytic leukemia, which may read out in early 2021. Failure to show superiority may not be as much of a setback, as the trial design first tests for non-inferiority before making a superiority analysis. In addition, BeiGene's CLL program includes a first-line trial against a bendamustine and Rituxan combination.