Lilly’s Jaypirca moves closer to European approval for relapsed chronic lymphocytic leukemia

Eli Lilly and Company (Lilly) has moved one step closer to securing European approval for its targeted blood cancer therapy, Jaypirca (pirtobrutinib), after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for its use in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). The recommendation applies to adults previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor, an important class of targeted drugs in CLL treatment.

The CHMP’s backing is based on findings from the Phase 3 BRUIN CLL-321 trial, which demonstrated that Jaypirca significantly improved progression-free survival (PFS) compared to standard treatment options. The European Commission will now review the application, with a final decision expected within the next two months.

Why is Jaypirca significant for relapsed CLL treatment?

Jaypirca, a non-covalent BTK inhibitor, represents a novel approach to treating CLL patients who have relapsed after prior BTK inhibitor therapy. Unlike covalent BTK inhibitors, which bind irreversibly to their target, Jaypirca is designed to provide continued BTK pathway inhibition even after resistance to earlier treatments develops.

The BRUIN CLL-321 trial is the first randomized Phase 3 study conducted exclusively in CLL patients who had previously been treated with a BTK inhibitor. The trial enrolled 238 patients, who were randomized to receive either Jaypirca or the investigator’s choice of two commonly used regimens: idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).

Data from the trial revealed that Jaypirca reduced the risk of disease progression or death by 46% compared to standard treatments, with a median progression-free survival of 14.0 months versus 8.7 months for the control group. These benefits were observed across various high-risk patient groups, including those with TP53 mutations, 17p deletions, and complex karyotypes—genetic markers often linked to poor prognosis.

Dr. Paolo Ghia, professor of medical oncology at Università Vita-Salute San Raffaele in Milan, Italy, noted that the therapy addresses a critical gap in treatment, offering continued BTK pathway inhibition for patients with limited options. He highlighted Jaypirca’s ability to delay disease progression in a patient population with significant unmet medical needs.

How does Jaypirca compare to existing treatment options?

Jaypirca’s efficacy in relapsed or refractory chronic lymphocytic leukemia sets it apart from standard therapies, which often fail to deliver sustained disease control in patients who have progressed on earlier treatments. The BRUIN CLL-321 trial demonstrated that Jaypirca significantly prolonged time to next treatment (TTNT), with patients in the Jaypirca arm achieving a median TTNT of 24 months, compared to 11 months in the control group.

Additionally, Jaypirca maintained its effectiveness in patients who had previously received venetoclax, another targeted therapy commonly used in CLL. Given the limited treatment options available for post-BTK inhibitor patients, the findings reinforce Jaypirca’s potential to become a preferred second-line or third-line therapy in this setting.

From a safety perspective, the drug’s profile was consistent with previous clinical trials, including the Phase 1/2 BRUIN study. The most commonly reported adverse reactions were neutropenia, fatigue, diarrhea, anemia, rash, and contusion, aligning with side effects seen in other BTK inhibitors.

What are the next steps for Jaypirca’s approval in Europe?

Following the CHMP’s positive opinion, the European Commission will evaluate Jaypirca’s application, with a decision anticipated within one to two months. If approved, Jaypirca will be available for relapsed or refractory CLL patients who have previously received a BTK inhibitor, further expanding treatment options in the European Union.

Jaypirca already holds conditional marketing authorization in Europe for the treatment of mantle cell lymphoma (MCL), another B-cell malignancy, in patients who have previously been treated with a BTK inhibitor. Outside of the EU, the drug was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2023 for patients with relapsed or refractory mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (SLL) after at least two prior lines of therapy.

Eli Lilly has also submitted supplemental marketing applications for Jaypirca across multiple regions, including the United States, to broaden its approval for post-BTK inhibitor treatment in CLL/SLL patients worldwide.

How could Jaypirca impact Eli Lilly’s market position?

Eli Lilly’s oncology portfolio has been expanding, with Jaypirca positioned as a key asset in its hematology division. The drug’s potential European approval strengthens Lilly’s presence in the blood cancer market, where BTK inhibitors have become a cornerstone of therapy.

Investor sentiment surrounding Jaypirca’s approval prospects remains positive, particularly given the drug’s ability to fill a major treatment gap in relapsed CLL. Eli Lilly and Company’s stock (NYSE: LLY) was trading at $905.16 as of February 28, 2025, reflecting stable performance ahead of the European Commission’s upcoming decision.

Jacob Van Naarden, executive vice president and president of Lilly Oncology, emphasized the significance of the CHMP’s recommendation, noting that no other treatment has been studied in a randomized Phase 3 trial specifically for this patient population. He expressed optimism that Jaypirca could become a meaningful new option for relapsed CLL patients across Europe.

What does this mean for CLL patients in Europe?

If approved, Jaypirca will provide a highly targeted and effective treatment option for CLL patients who have relapsed on earlier BTK inhibitor therapy. The drug’s ability to prolong disease control and delay disease progression addresses a pressing need for new treatment strategies in advanced CLL.

For oncologists and hematologists, Jaypirca represents an important addition to the treatment landscape, offering an alternative to traditional chemotherapy-based regimens. Its success in the BRUIN CLL-321 trial highlights its potential role in treatment sequencing, particularly for patients who may not tolerate covalent BTK inhibitors or have developed resistance.

As the European Commission prepares to issue its final ruling, patients and clinicians alike will be watching closely, hoping for a new treatment option that can significantly improve outcomes for those with relapsed or refractory chronic lymphocytic leukemia.