BeiGene’s Phase III Waldenström’s study misses mark, but with a possible silver lining

The Phase III study showed that BeiGene’s Brukinsa outperformed AbbVie and J&J’s Imbruvica on safety. An analyst wrote that FDA approval on that basis is unlikely, but off-label prescribing is possible. Brukinsa won approval for another blood cancer last month.

A Chinese biotech company that just won Food and Drug Administration approval for its lead candidate in a type of lymphoma missed the mark in a Phase III study of the drug in another disease, but some analysts are nevertheless calling it a win.

Beijing-based BeiGene said Monday that the Phase III ASPEN study of Brukinsa (zanubrutinib) in the rare blood cancer Waldenström’s macroglobulinemia, or WM, did not meet its primary endpoint of showing statistically significant improvement in efficacy over an already approved drug in the same chemical class, AbbVie and Johnson & Johnson’s Imbruvica (ibrutinib). The FDA granted Brukinsa accelerated approval for mantle cell lymphoma (MCL) patients who have received at least one prior therapy last month. Brukinsa and Imbruvica are both BTK inhibitors.

Shares of BeiGene were down more than 7% on the Nasdaq Monday afternoon.

ASPEN’s primary endpoint was efficacy, as measured by the rate of patients who achieved a complete response or very good partial response, also known as CR and VGPR, respectively. While no patients in the study achieved a CR, the VGPR rates for the Brukinsa and Imbruvica arms were respectively 28.9% and 19.8%. However, despite the rate being numerically higher for Brukinsa, it did not achieve statistical significance. Rates of overall survival and progression-free survival at 12 months were also somewhat higher for BeiGene’s drug, though the study was not powered to show a difference in OS or PFS, which are stronger endpoints than response rates.

Still, despite missing the mark on efficacy, ASPEN showed Brukinsa outperforming Imbruvica on safety. Brukinsa showed a lower rate of life-threatening or fatal side effects, 58.4% versus 63.3%. Four patients on Brukinsa dropped out of the study due to side effects, and one patient died, compared with nine adverse event-related dropouts and four fatal adverse events in the Imbruvica arm.

BeiGene said it plans to take the findings from ASPEN to regulators to discuss further steps. However, in a note to investors, Cowen analyst Yaron Werber wrote that it is unlikely the FDA will approve Brukinsa for WM based on the ASPEN data, though some off-label sales are anticipated.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

Imbruvica had sales of $3.6 billion in 2018, according to AbbVie. It is currently approved for MCL and WM, along with chronic lymphocytic leukemia, marginal zone lymphoma and chronic graft-versus-host disease. Brukinsa is also being developed in CLL, MZL and follicular lymphoma.

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