BeiGene has shared updated findings from a Brukinsa head-to-head trial against Imbruvica, and it's not looking good for the heavyweight cancer therapy from AbbVie and Johnson & Johnson.
Brukinsa is beating Imbruvica left and right in a phase 3 trial in previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to a data set to be presented at the American Society of Hematology annual meeting in December.
By an independent review committee, the BeiGene drug cut the risk of tumor progression or death by 35% over Imbruvica, reaching superiority against its first-in-class BTK inhibitor rival. An analysis by investigators reported “identical statistical values,” an abstract shows.
Patients on Imbruvica went a median 35 months without disease progression, the independent data review board found. By comparison, the median length of progression-free survival (PFS) was not yet reached for patients in the Brukinsa arm, meaning more than half were still alive and free of disease progression at the time of the data cutoff.
The latest PFS win follows a previous tumor response showing for Brukinsa against Imbruvica in the same phase 3 ALPINE trial, and it adds more weight to the notion that Brukinsa is a better BTK inhibitor than AbbVie and J&J’s first-generation BTK option.
And, because AstraZeneca’s rival BTK drug Calquence had previously only showed efficacy noninferiority to Imbruvica, Brukinsa is now the first BTK inhibitor to top Imbruvica on a hard efficacy endpoint.
When BeiGene announced the trial success in October—without sharing specifics of the data—SVB Securities analyst Andrew Berens, M.D., put Brukinsa’s 2030 sales estimate at $3.6 billion, including $2.8 billion from outside of China.
Brukinsa’s attack on Imbruvica comes from all fronts. In the updated readout, Brukinsa’s tumor response rate remained higher at 86.2%, versus Imbruvica’s 75.7% by independent review.
In a prespecified subgroup of patients with the hard-to-treat del(17p)/TP53 mutation, Brukinsa pared down the risk of disease worsening or death by 48% versus Imbruvica. On the PFS endpoint, data “consistently favored” Brukinsa across other major predefined subgroups, the ALPINE study authors wrote in the abstract.
Overall, 48 patients (14.7%) treated with Brukinsa in the trial had died, compared with 60 patients (18.5%) in the Imbruvica arm. That equated to a 24% reduction in the risk of death, although the number didn’t bear statistical significance.
In addition to efficacy, BeiGene has also touted Brukinsa’s better safety profile as it tries to challenge Imbruvica’s market-leading position. In ALPINE, 41.2% of Imbruvica takers discontinued treatment, including 22.8% because of side effects. Both rates were lower for Brukinsa, at 26.3% and 16.2%, respectively.
Cardiovascular side effects, including potentially life-threatening problems, have been tied to the BTK drug class. There, Brukinsa once again showed it’s better than Imbruvica.
The rates of irregular heartbeats, known as atrial fibrillation and flutter, were 5.2% and 13.3% for Brukinsa and Imbruvica, respectively. Six patients (1.9%) in the Imbruvica arm died of drug-related heart disorders, whereas investigators recorded none for the Brukinsa group.
A better safety profile also positions Brukinsa well for potential combinations. BeiGene is testing Brukinsa alongside its own PI3K inhibitor BGB-10188 in various B-cell malignancies and has also partnered with MEI Pharma’s PI3K drug zandelisib. A third cohort of the phase 3 SEQUOIA trial in newly diagnosed CLL/SLL is pairing Brukinsa with AbbVie and Roche’s Venclexta, and BeiGene is developing its own BCL-2 inhibitor BGB-11417, also with the intention to combine it with Brukinsa.
The Imbruvica head-to-head data in second-line patients, plus the positive SEQUOIA readouts in the front-line setting, earned Brukinsa its CLL/SLL approval in Europe a few days ago. Because of the latest ALPINE tumor progression data update, the FDA previously extended its review by three months, with a decision now targeted for Jan. 20.
BeiGene has argued Brukinsa is better than Imbruvica, but until ALPINE the company has only been able to show limited success in a small blood cancer indication. The new data will definitely add more pressure to Imbruvica, which is already experiencing sales declines.
While still maintaining its market leadership position thanks to a multiyear head start, Imbruvica revenues dropped 7.2% worldwide at constant currencies to $911 million for J&J in the third quarter. In the U.S., AbbVie reported a dramatic 23.5% year-over-year decrease during the third quarter to $849 million.
Both Brukinsa and AstraZeneca’s Calquence delivered sales gains during the same period. AstraZeneca’s Calquence has also previously shown a heart safety advantage over Imbruvica, but only noninferior efficacy in a head-to-head manner.