Jaypirca chalked up its fourth positive phase 3 readout in chronic lymphocytic leukemia on Monday, and this one rewrites the treatment calculus: it’s the first CLL trial to beat a venetoclax-based regimen.
Eli Lilly’s phase 3 Bruin CLL-322 tested Jaypirca added to a fixed-duration venetoclax and rituximab regimen in patients with previously treated CLL or small lymphocytic lymphoma. The combination significantly extended progression-free survival compared to venetoclax-rituximab alone. Venetoclax, an oral BCL-2 inhibitor sold as Venclexta by Roche and AbbVie, is the standard second-line anchor in the disease.
The trial also showed an overall survival trend favoring the Jaypirca combo, though that endpoint wasn’t yet mature. Rates of adverse events and treatment discontinuations were similar between arms.
The commercial implications land hard. Jaypirca’s prior FDA approval in second-line CLL was based on indefinite use until progression, which put it at a disadvantage against time-limited venetoclax regimens when no head-to-head comparison existed. That’s changed. Lilly Oncology president Jacob Van Naarden said the results “outperformed our expectations.”
Jaypirca is a non-covalent BTK inhibitor, meaning it can work in patients who’ve already failed covalent BTK drugs like BeOne’s Brukinsa, AbbVie and J&J’s Imbruvica, or AstraZeneca’s Calquence. That’s a growing pool as covalent BTKs move to the front line. Results were consistent across subgroups regardless of prior covalent BTK exposure, strengthening the filing case.
Lilly plans to file for approval this year. In February, AstraZeneca’s Calquence-Venclexta combo became the first all-oral, fixed-duration regimen cleared for first-line CLL in the U.S.
Sarah Chen