Lilly's Jaypirca Outperforms Johnson & Johnson/AbbVie's Imbruvica in Head-to-Head Phase 3 Trial for CLL/SLL

Lilly announced重磅消息, its drug Jaypirca (pirtobrutinib) in the first-ever head-to-head Phase III clinical trial BRUIN CLL-314, compared to the standard therapy from Johnson & Johnson / AbbVieIbrutinib Imbruvica (ibrutinib) achieved positive results. This trial focused on treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), who were either treatment-naive or had not previously received a BTK inhibitor. CLL and SLL are slow-growing non-Hodgkin lymphomas that originate from white blood cells called lymphocytes.

Jaypirca is a novel non-covalent (reversible) BTK inhibitor, while Imbruvica is a covalent BTK inhibitor. BTK is a validated molecular target in many B-cell leukemias and lymphomas, including CLL/SLL and mantle cell lymphoma. Jaypirca demonstrates high selectivity, showing 300 times greater selectivity for BTK than 98% of other kinases tested in preclinical studies. The BRUIN CLL-314 study is a randomized, open-label trial that enrolled a total of 662 patients, receiving either Jaypirca (331 patients) or ibrutinib (331 patients).

The trial results showed that Jaypirca successfully met the primary endpoint, which was non-inferiority to ibrutinib in terms of overall response rate (ORR). Across all "intention-to-treat" (ITT) populations, Jaypirca demonstrated a numerically higher ORR of 87.0%, compared to 78.5% for ibrutinib. The Independent Review Committee (IRC) assessment confirmed statistical non-inferiority with numerical favorability towards Jaypirca. BRUIN CLL-314 is the first randomized study comparing covalent and non-covalent BTK inhibitors and represents the first direct comparison of the efficacy of any BTK inhibitors in a frontline treatment setting.

Although the data for the key secondary endpoint of progression-free survival (PFS) were not yet mature at the time of this analysis, the overall trend favored pirtobrutinib. In the ITT population, the risk of disease progression or death was reduced by 43%. Particularly in the treatment-naïve patient subgroup (which had the longest follow-up as of the data cutoff date of June 10, 2025), the largest PFS effect was observed, with a 76% reduction in the risk of disease progression or death. Additionally, ORR results consistently favored Jaypirca across all predefined subgroups, including treatment-naïve, relapsed/refractory patients, and those with del(17p), IGHV status, or complex karyotype.

In terms of safety, the overall safety profile of Jaypirca was similar to previously reported trials. However, compared with ibrutinib, the incidence of most adverse events of concern in the Jaypirca group was lower. For instance, the incidence of atrial fibrillation/flutter was significantly lower than that of ibrutinib (2.4% vs 13.5%), and the incidence of hypertension was also lower (10.6% vs 15.1%). Additionally, the proportion of dose reductions (7.9% vs 18.2%) and permanent discontinuations (9.4% vs 10.8%) due to adverse events was lower in the Jaypirca group. These positive efficacy and safety results provide strong evidence for Jaypirca playing a role in the early treatment of CLL or SLL.

Currently, Jaypirca has been approved by the U.S. FDA for the treatment of adult patients with relapsed or refractory CLL/SLL who have previously received covalent BTK inhibitor therapy. It is also used to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.

Eli Lilly and Company plans to share these new findings at the 2025 American Society of Hematology (ASH) Annual Meeting and simultaneously publish them in the Journal of Clinical Oncology.