BeiGene nabs landmark FDA nod for Brukinsa, kicking off challenge against blockbuster Imbruvica

With its Brukinsa approval Thursday, BeiGene racked up a couple of firsts: Its own first FDA green light and the first FDA nod for a cancer drug discovered in China. And both came months ahead of schedule.

The new BTK inhibitor, also known as zanubrutinib, won accelerated approval in previously treated adults with mantle cell lymphoma (MCL). With plans to launch Brukinsa in the coming weeks, BeiGene will be squaring off against AbbVie and Johnson & Johnson’s first-to-market blockbuster Imbruvica and AstraZeneca’s up-and-coming Calquence. And the Chinese biotech hopes it can emerge a winner.

BeiGene is pricing Brukinsa at the whole sale acquisition price of $12,935 for a 30-day supply, a company spokesperson told FiercePharma. That comes on par with Imbruvica tablets' current tag but below Calquence's around $14,000.

The FDA’s decision is largely based on tumor shrinkage data from a phase 2 trial in 86 Chinese patients. In that single-arm study, Brukinsa triggered an overall response rate of 84% with a median duration of response of 19.5 months. Some 59% of patients saw a complete response, meaning their cancers were undetectable after treatment.

The drug’s performance was also supported by a global phase 1/2 trial outside of China, in which 84% of patients also saw their tumors shrink, including a 22% rate of complete responses.

BeiGene is currently running a confirmatory phase 3 trial, pairing Brukinsa with Roche’s Rituxan against the combo of Treanda (bendamustine) and Rituxan in new patients with MCL who are ineligible for stem cell transplantation.

Brukinsa’s numbers “appear compelling relative to Imbruvica (66% ORR, 17% CR) and Calquence (81% ORR, 40% CR),” SVB Leerink analyst Andrew Berens noted in a September report to clients. However, cross-trial comparisons can be problematic as patient profiles—such as stages of disease—and trial designs can differ.

First approved in previously treated MCL in 2013, Imbruvica is the clear leader in the BTK class, backed up by additional green lights in Waldenström macroglobulinemia (WM), chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), among others. In the third quarter alone, the drug returned $1.26 billion in revenues (including profit sharing with J&J) for AbbVie, growing 30% year over year.

Calquence, approved by the FDA in MCL late 2017 and under review in CLL, racked up $108 million in the first nine months of 2019. Berens’ team now expects Brukinsa to enjoy a faster ramp-up with 2021 sales of $220 million and then to $2.20 billion by 2025.

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BeiGene has made clear its intention to come after Imbruvica with potentially better efficacy and safety profiles, so much so that it’s running costly phase 3 head-to-head studies to prove its case.

Clues could come later this year from the phase 3 Aspen trial, which pits Brukinsa against Imbruvica in WM. That data release is now considered “the largest binary event in our targeted oncology universe,” SVB Leerink analysts said.

While WM is a small indication, the Aspen trial could provide “confirmation that zanubrutinib is a differentiated BTK drug able to compete on a global level,” Berens said in a November note.

In addition to beating Imbruvica in terms of complete response and very good partial response rates—the study’s primary endpoint—BeiGene is also looking to show some superiority on safety. The drug was designed to maximize its targeted effect and minimize action elsewhere, Jane Huang, chief medical officer of hematology at BeiGene, said in a statement.

As Berens sees it, “the safety and tolerability profile are as important as the efficacy data […] as the Achilles heel for Imbruvica is not the lack of efficacy, but the relatively high rates of atrial fibrillation and major hemorrhage,” he said in an October preview of Aspen.

Brukinsa’s current label states that grade 3 or higher bleeding events showed up in 2% of patients treated with the drug, and atrial fibrillation and atrial flutter have occurred in 2% of patients. In comparison, Imbruvica’s label shows 4% for both adverse events.

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Apart from Aspen, BeiGene last year initiated the phase 3 Alpine trial, comparing Brukinsa to Imbruvica in relapsed/refractory CLL. The company is also providing two sets of new data in CLL/SLL at the upcoming American Society of Hematology annual meeting in December.

The Brukinsa nod also bears other significance beyond the drug itself, Berens said in a Friday note to clients. It “provides validation of the pathway for drug approval based primarily on data generated from China,” he said.

For BeiGene specifically, the approval suggests the company could speed U.S. filing of its PD-1 drug tislelizumab based on China data in non-small cell lung cancer. Richard Pazdur, director of the FDA’s Oncology Center of Excellence, has previously indicated that the agency is willing to consider PD-1 inhibitors based solely on data generated in China.

BeiGene has gone through an eventful year so far. First, its founder and helmsman John Oyler’s hefty 2018 pay package of $27.9 million raised some eyebrows among investors. After Opdivo developer Bristol-Myers Squibb unveiled its $74 billion acquisition of BeiGene’s PD-1 partner Celgene, the Chinese biotech is now developing tislelizumab on its own.

Then, it fought off a U.S.-based short-seller's accusation that the company had faked sales figures in China—that, and a $2.7 billion tie-up from Amgen that covers drug development and commercialization, largely cleared BeiGene’s name.

Editor's Note: The story has been updated with Brukinsa's WAC.