As a latecomer, BeiGene must win over a meaningful share of the all-important chronic lymphocytic leukemia market to stay relevant in the BTK game. Now, the Chinese drugmaker has early data showing its Brukinsa could be a better option than AbbVie and Johnson & Johnson’s market-leading Imbruvica in this field.
In a study of previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Brukinsa shrunk tumors in more patients than Imbruvica did while causing fewer incidents of a dangerous heart side effect than its first-to-market rival, according to data unveiled at the European Hematology Association’s virtual congress.
BeiGene’s discussing the head-to-head data, from the phase 3 ALPINE trial, with health authorities, BeiGene’s chief medical officer of hematology, Jane Huang, M.D., said in an interview. Because the company’s also expecting top-line data from the phase 3 Sequoia trial for newly diagnosed patients later this year, “there may be opportunities” that the company could file both sets of data together, she added.
It wouldn’t be unprecedented, AstraZeneca’s rival BTK inhibitor Calquence did win FDA nods simultaneously for previously untreated and relapsed or refractory CLL/SLL in late 2019. As SVB Leerink analyst Andrew Berens put it in an investor note in May, positive ALPINE results would be “critical for [Brukinsa’s] commercial positioning against well-entrenched Imbruvica and Calquence.”
The interim data do look promising for BeiGene. By investigator analysis of tumor response, which is ALPINE’s primary endpoint, Brukinsa triggered a response in 78.3% of patients, significantly more than Imbruvica’s 62.5% after a median 15 months of follow-up. But when analyzed by an independent data review committee, the BeiGene drug’s efficacy edge narrowly missed the statistical significance bar, with the response rates at 76.3% and 64.4% for Brukinsa and Imbruvica, respectively, Huang said.
Myriad factors may have caused the discrepancy between the two assessments, Huang explained. Independent reviewers only look at the scans and some lab results and therefore don’t have the full clinical picture of a patient when deciding whether a tumor is growing, she said.
This isn’t the first time Brukinsa has narrowly missed a superiority efficacy mark in a head-to-head trial against Imbruvica. In the phase 3 Aspen study in patients with Waldenström macroglobulinemia, Brukinsa only showed a numeric advantage in provoking complete or “very good” partial responses. At the time, Berens attributed the miss to the trial’s statistical powering and outperformance for the Imbruvica arm.
Data on whether Brukinsa beats Imbruvica at staving off cancer progression remain immature at the moment, but they’re trending in the BeiGene drug’s favor. At the one-year mark, 94.9% of Brukinsa patients were still alive without disease worsening, versus 84% of patients in the Imbruvica arm. That’s translated into a preliminary risk reduction of 60%.
Brukinsa did demonstrate a clear safety edge in atrial fibrillation, an irregular heartbeat that can increase the risk of serious complications such as stroke and heart failure. In ALPINE, 2.5% of Brukinsa patients suffered atrial fibrillation, significantly lower than the 10.1% for the Imbruvica group.
And while seven Imbruvica patients had their treatment disrupted thanks to different cardiac disorders, none in the Brukinsa arm did. All told, 7.8% of Brukinsa patients stopped treatment because of side effects, compared with 13% of the Imbruvica group.
The safety showing is important, especially for chronic drugs like BTK inhibitors that patients take every day for years, because compared with other “annoying” side effects, cardiac events like atrial fibrillation can be life-threatening, Huang said.
“With BTK treatment, we know that … the majority of patients will rebound in their disease if they can’t stay on the drug,” she said.
Both Brukinsa and AZ’s Calquence are trying to eat into Imbruvica’s BTK lead, especially in CLL. Calquence also boasts a head-to-head heart safety win in previously treated CLL from the phase 3 Elevate-RR trial. After 40.9 months of follow-up, the rates of atrial fibrillation were 9.4% for Calquence and 16% for Imbruvica, according to data presented at the recent American Society of Clinical Oncology annual meeting.
Without a U.S. approval in CLL, Brukinsa’s sales were a meager $22.1 million in the first quarter, an underperformance thanks in part to price compensations to distributors in China before its official inclusion in the National Reimbursement Drug List.
But Berens sees a multi-blockbuster asset in Brukinsa, having pegged its 2025 sales at $4.79 billion. Last year, Imbruvica hauled in global sales of $8.43 billion for AbbVie and J&J.