Look out, AbbVie and J&J. BeiGene's Brukinsa just scored a key leukemia nod to take on Imbruvica

Armed with a new FDA approval in chronic lymphocytic leukemia (CLL), BeiGene is readying an all-out assault against AbbVie and Johnson & Johnson’s entrenched Imbruvica.

After a short delay, the FDA has signed off on Brukinsa to treat CLL or small lymphocytic lymphoma (SLL), BeiGene said Thursday.

The new nod allows Brukinsa to officially challenge AbbVie and J&J’s market-leading Imbruvica—and AstraZeneca’s Calquence—in the largest indication for the three BTK inhibitors. And Brukinsa boasts an Imbruvica head-to-head win to back its case.

In patients with previously treated CLL/SLL, Brukinsa shrank tumors in more patients than Imbruvica did in the phase 3 ALPINE trial. Although not included in Brukinsa’s new label, an updated analysis published in December showed that Brukinsa also significantly cut the risk of cancer progression or death by 35% over Imbruvica. What’s more, the BeiGene drug also showed significantly lower rates of irregular heartbeats known as atrial fibrillation or flutter, a known side effect of the BTK inhibitor class.

Brukinsa’s superior ability to stave off progression and a better cardiac toxicity profile in a patient population who typically are in their 60s and 70s suggest the drug is a practice-changing treatment in relapsed or refractory CLL, Mehrdad Mobasher, M.D., BeiGene’s hematology chief medical officer, said in an interview with Fierce Pharma last month.

Based on the head-to-head trial win, SVB Securities analysts in October projected $3.6 billion sales for Brukinsa by 2030, including about $2.8 billion from outside of China.

Separately, in newly diagnosed patients, Brukinsa reduced the risk of disease progression or death by 58% versus the combination of bendamustine and Rituxan in the phase 3 SEQUOIA trial.

Before the all-important CLL nod, Brukinsa had been approved in the U.S. for smaller indications, including Waldenström’s macroglobulinemia, previously treated mantle cell lymphoma and marginal zone lymphoma. BeiGene has been pitching Brukinsa as the BTK inhibitor of choice, but it was only until the ALPINE readout that the company had mature evidence to show Brukinsa is better than Imbruvica.

Brukinsa’s superiority over Imbruvica also gives the BeiGene med an upper hand in its competition with Calquence. In its own head-to-head trial with Imbruvica, the AZ drug only showed noninferior efficacy.

Facing dual threats from Brukinsa and Calquence, Imbruvica started bleeding market share even before Thursday’s nod. For the third quarter, AbbVie reported a 23.5% Imbruvica U.S. sales decline year over year to $849 million.

In another blow to Imbruvica, the influential National Comprehensive Cancer Network (NCCN) in August updated its CLL/SLL guidance. Experts there kicked Imbruvica off the “preferred regimens” list across treatment settings and noted the drug’s toxicity. By comparison, Brukinsa is a preferred regimen with the highest (category 1) NCCN recommendation, which suggests uniform consensus based on strong evidence.

One thing that Brukinsa doesn’t yet have is superiority on patient overall survival. In the ALPINE trial, Brukinsa cut the risk of death by 24% compared with Imbruvica, but that didn’t bear statistical significance.

Still, progression-free survival is viewed as the gold standard in CLL, particularly because BTK inhibitors are given until disease progression or unacceptable toxicity, BeiGene’s Mobasher said in the interview. And because the median age of CLL patients is 72, “it becomes even more important to be able to deliver a treatment that [shows] advantage in progression-free survival and is more tolerable,” he added.

Meanwhile, AbbVie and J&J are working on differentiating Imbruvica from the dosing angle. Instead of continuous dosing, the European Commission in August approved a fixed-duration combination of Imbruvica and AbbVie's BCL-2 inhibitor Venclexta for front-line treatment of CLL.

BeiGene is working its own BCL-2 inhibitor, which the company hopes could follow the Brukinsa-Imbruvica storyline and beat Venclexta on both efficacy and safety. The drug, coded BG-11417, has shown promising results in early-stage testing. A potential combination of Brukinsa and the BCL-2 drug for front-line CLL is in the cards, Mobasher said.