Pirtobrutinib receives positive CHMP opinion for the treatment of adult patients with R/R CLL and previous BTKi exposure

On February 28, 2025, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion and recommendation for the approval of pirtobrutinib for the treatment of adult patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.¹

This decision was based on data from the phase III BRUIN CLL-321 (NCT04666038) trial, the first trial conducted exclusively in patients with prior exposure to a BTK inhibitor.¹

The trial’s primary endpoint of progression-free survival (PFS) was met, based on independent review committee (IRC) assessment, during the final analysis in August 2023.¹ An updated analysis from the BRUIN CLL-321 trial was presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2024 by Sharman.²

BRUIN CLL-32 pivotal data²

• Pirtobrutinib reduced the risk of disease progression or death by 46% compared to idelalisib in combination with rituximab or bendamustine-rituximab (IdelaR/BR), with a median PFS of 14.0 months compared to 8.7 months, respectively.
• PFS benefits were observed across key subgroups, including patients with prior venetoclax treatment and those with high-risk genetic features such as TP53 mutations and 17p deletions.
• Median time to next treatment or death was 24.0 months with pirtobrutinib compared to 10.9 months with IdelaR/BR, giving a hazard ratio of 0.37 (p < 0.0001).
• 18-month overall survival was 73.4% with pirtobrutinib, compared to 70.8% with IdelaR/BR.
• The safety profile of pirtobrutinib was consistent with previous data from the phase I/II BRUIN study, including known adverse events of special interest.
• The most common adverse reactions of any grade were neutropenia, fatigue, diarrhea, anemia, rash, and contusion.