BeiGene’s Brukinsa wins CLL approval after topping Imbruvica in head-to-head trial

The FDA greenlit BeiGene’s Brukinsa for use in chronic lymphocytic leukemia, an approval that should substantially expand the market for the drug in the US after it topped the current leading therapy in a trial.

The approval, which is for relapsed/refractory and first-line treatment for adults with CLL as well as small lymphocytic lymphoma, is the drug’s fourth US clearance. It comes after BeiGene showed the twice-daily oral drug beat the standard of care, AbbVie and Johnson & Johnson’s Imbruvica, in a head-to-head test.

“This is the most important for BeiGene,” Mehrdad Mobasher, who replaced Jane Huang last year as the biotech’s CMO for hematology, told Endpoints News before the FDA decision. “CLL is the most common leukemia in adults.”

BeiGene has been counting on the ruling as a crucial step to significantly expanding its US sales, and to help the company realize its ambitions of expanding further in cancer as well as other areas. And while the data are strong, the company will be up against an entrenched competitor.

Through the first three quarters of 2022, BeiGene racked up $388.5 million in global revenue for Brukinsa, according to financial reports. Imbruvica’s global net revenues were $3.45 billion in the same period and Calquence brought in $1.46 billion in worldwide revenue in that nine-month stretch.

Imbruvica has been on the market for close to nine years and garnered eye-popping headlines for AbbVie’s $21 billion purchase of Pharmacyclics in 2015. AstraZeneca followed suit half a year later with a multibillion dollar purchase of the second-gen BTK inhibitor, Acerta’s Calquence, which was brought through the clinic by many of the leaders who led Imbruvica’s early investigational plans.

Head-to-head trial

Trial investigator Jennifer Brown said the safety of Brukinsa was also better than Imbruvica, including a lower rate of cardiac disorders. Brown, who is also the director of the Dana-Farber Center for Chronic Lymphocytic Leukemia, told reporters at last month’s American Society of Hematology meeting that she doesn’t think there’s a group of CLL patients for whom Imbruvica would remain the standard.

In the ALPINE study of about 650 patients, the rate of progression-free survival was 79.5% for patients on BeiGene’s drug and 67.3% for those on Imbruvica at 24 months. In the relapsed/refractory setting, BeiGene said 80.4% of patients on Brukinsa responded, versus 72.9% on Imbruvica, with a p-value of 0.0264.

In a different Phase III trial, dubbed SEQUOIA, BeiGene had shown that Brukinsa led to a better progression-free survival than the combo of the cancer drugs bendamustine and Rituxan.

Brukinsa landed its first FDA win in November 2019 for patients with the rare, aggressive blood cancer known as mantle cell lymphoma. Another nod came in August 2021 for a rare form of lymphoma known as Waldenström’s macroglobulinemia, despite Brukinsa failing in a head-to-head against Imbruvica.

A month later, in September 2021, FDA expanded the label to include adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.

Mehrdad Mobasher

It’s good for an elderly population to have “more medications and more tolerable treatments,” he added.

The National Comprehensive Cancer Network also showed its preference for Brukinsa in recent months, ahead of the expanded label, updating its guidelines to recommend physicians choose the drug before Imbruvica for treating CLL.

The European Commission approved the drug for CLL in November. Across the board, Brukinsa is approved in more than 60 markets and has been studied in more than 30 clinical trials, BeiGene said.

Company ambitions

“Most of our time is spent looking at oncology because this is our strength,” Beigene CEO John Oyler told Endpoints at the JP Morgan healthcare conference in San Francisco earlier this month. “We’re starting to look in other areas that are tangential to this and other things we could do to leverage some of the infrastructure we have.”

About 20,000 new cases of the specific lymphoma were expected in 2022, according to Dana-Farber. CLL is when cancer cells populate in the bone marrow and bloodstream, whereas with small lymphocytic the cancer is mainly in the lymph nodes.

Brukinsa and Imbruvica are both covalent Bruton’s tyrosine kinase inhibitors, which aim to block a protein that helps send signals that drive the growth of leukemia and lymphoma cells. If the protein signal is blocked in B cells, then the cancer cells should be wiped away, researchers believe. But Imbruvica has been shown to have off-target effects, meaning it impairs not just the BTK protein.

The next generation of BTK inhibitors, ones that don’t covalently bond, could come to market soon. Early this year, the FDA is set to decide whether to approve Eli Lilly’s pirtobrutinib in BTK pre-treated mantle cell lymphoma patients.

Paul Schloesser contributed reporting. 

Editor’s note: CLL is an abbreviation for chronic lymphocytic leukemia, not lymphoma.

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