Jaypirca Matches Imbruvica's Effectiveness for CLL, With Hints of Long-Term Benefit

Jaypirca (pirtobrutinib) was found to have similar efficacy as Imbruvica (ibrutinib) in improving clinical efficacy in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These positive findings came from the phase 3 BRUIN CLL-314 trial (NCT05254743), which compared the two drugs head-to-head in both patients who had never before received a BTK inhibitor, a specific type of targeted therapy, as well as those with relapsed/refractory disease.

The results, presented by Dr. Jennifer Woyach at the 2025 ASH Annual Meeting, also showed that Jaypirca showed a promising trend toward better long-term control of the disease.

The study looked at two main groups of patients: those who were newly diagnosed, known as treatment naive, and those whose disease had come back or resisted previous treatment, known as relapsed/refractory. Overall, 662 patients were randomly assigned to receive either Jaypirca or Imbruvica.

In all patients treated, the objective response rate (ORR) for Jaypirca was 87% compared with 78.5% for Imbruvica. This demonstrated that Jaypirca was noninferior, or not worse than, Imbruvica, and also showed consistently higher response rates across all patient groups. The best response (complete response [CR] or CR with incomplete blood recovery) was achieved by 4.8% of patients on Jaypirca versus 2.4% on Imbruvica.

Woyach noted that Jaypirca showed a higher ORR in both the treatment-naive population (92.9% vs. 85.8%) and the relapsed/refractory population (84.0% vs. 74.8%).

While it is still early, data on progression-free survival (PFS) — the time patients live without their disease worsening — showed a trend favoring Jaypirca.

In all patients studied, the percentage of patients alive without their disease progressing at eighteen months was 86.9% for Jaypirca versus 82.3% for Imbruvica.

At eighteen months, 95.3% of newly diagnosed patients on Jaypirca were alive without their disease progressing, compared with 87.6% of those on Imbruvica.

Woyach explained that this early trend in PFS was most pronounced in the treatment-naive group, where patients have been followed for the longest period.

Jaypirca was generally well tolerated by patients, with fewer patients needing to reduce their dose or stop the drug due to side effects compared with Imbruvica.

Atrial fibrillation/flutter occurred at a rate of 2.4% with Jaypirca, which was substantially lower than the 13.5% seen with Imbruvica. This difference was even greater in patients aged 75 or older (4.5% with Jaypirca vs. 21.4% with Imbruvica).

Common side effects of any grade for Jaypirca included low white blood cell count, upper respiratory infections, anemia, and pneumonia.

Rates of hypertension were also lower with Jaypirca compared with Imbruvica.

BRUIN CLL-314 is the first to directly compare Jaypirca and Imbruvica in patients who have not previously received a BTK inhibitor.

Currently, Jaypirca is approved by the FDA for patients with relapsed or refractory CLL/SLL who have already been treated with another BTK inhibitor.

Woyach noted that as the PFS data continue to mature and uphold the trend favoring Jaypirca, these findings will support a request to the FDA to use the drug as a first-line treatment for CLL/SLL.

Reference

1. "Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor" by Jennifer Woyach et al., Blood.