In a comparison trial, BeiGene’s Brukinsa bested Janssen’s Imbruvica in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).
Courtesy of BeiGene
In a head-to-head comparison trial, BeiGene’s Brukinsa (zanubrutinib) bested Janssen’s Imbruvica (ibrutinib) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).
In the Phase III ALPINE trial, patients treated with Brukinsa saw a 35% lower risk of disease progression or death, as assessed by investigators, relative to comparators treated with Imbruvica. After 24 months of follow-up, progression-free survival rates were 78.4% and 65.9% in patients given BeiGene’s and Janssen’s respective therapeutics.
The findings were published Tuesday in the New England Journal of Medicine and presented at a late-breaking session at the 64th American Society of Hematology (ASH) Annual Meeting.
BeiGene has submitted a supplemental New Drug Application for Brukinsa in CLL, with an FDA target action date of January 20, 2023.
Jennifer Brown, lead study author and director of the CLL Center at the Dana-Farber Cancer Institute, said these results “provide compelling evidence for Brukinsa as a practice-changing Bruton’s tyrosine kinase (BTK) inhibitor” in CLL management, adding that “PFS is the gold standard for measuring efficacy in CLL clinical trials.”
In ALPINE, Brukinsa demonstrated a superior clinical profile overall and across different patient subgroups. In a sub-analysis of patients harboring a 17p deletion, a TP53 mutation or both, Brukinsa outperformed Imbruvica, leading to a nearly 50% reduction in the risk of progression or death.
ALPINE is a randomized global study enrolling more than 650 patients from Europe, the U.S., China, New Zealand and Australia. Brukinsa was dosed at 160 mg taken orally twice a day, while Imbruvica was given as 420-mg once-daily oral doses.
The study’s primary endpoint was overall response rate, which was also significantly higher in the Brukinsa arm at 80.4%, as opposed to 72.9% in the Imbruvica group.
Aside from efficacy, ALPINE also compared Brukinsa and Imbruvica in terms of safety and found a lower rate of treatment discontinuation due to side effects associated with BeiGene’s drug. Cardiac toxicities were also much more infrequent in the Brukinsa arm, particularly episodes that led to discontinuation.
No Brukinsa-treated patients died of cardiac events, while fatal events were reported in six patients in the Imbruvica group.
Challenging Impressive Imbruvica
Demonstrating significant PFS superiority over Imbruvica is no small feat, given that Janssen’s drug is an established frontrunner in the CLL therapeutic space.
In a recent interview with BioSpace, Mark Wildgust, vice president, global medical affairs, oncology at Janssen said Imbruvica is the only BTK inhibitor with a proven single-agent survival benefit for newly diagnosed CLL. In this indication alone, there are more than 80 ongoing trials testing Imbruvica in various drug combinations and dosing regimens.
Also at the 64th ASH, for instance, follow-up results from the Phase III GLOW study in CLL revealed that Imbruvica combined with AbbVie’s Venclexta (venetoclax tablets) cut the risk of disease progression or death by 79% relative to chlorambucil plus obinutuzumab.
The test combo also yielded better overall survival than chlorambucil plus obinutuzumab, so much so that treated patients saw similar survival rates to age-matched healthy comparators in the U.S.
“To be able to return survival back to potentially what we would see in the normal patient population, I think speaks to the transformational outcomes we’ve been hoping for,” Wildgust said. “In many regards, it’s almost like a functional cure.”
