FDA approves Jaypirca , the first and only non-covalent (reversible) BTK inhibitor, for adult patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor.- Loxo@Lilly/Eli Lilly.

Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase I/II study, called the BRUIN trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Jaypirca, a highly selective kinase inhibitor, utilizes a novel binding mechanism and is the first and only FDA approved non-covalent (reversible) BTK inhibitor. Jaypirca can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the BTK pathway.

The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, second primary malignancies, and embryo-fetal toxicity.

"We are pleased to bring a meaningful new therapeutic option to patients with MCL that can reestablish the benefit of targeting the BTK pathway after receiving multiple prior therapies, including a covalent BTK inhibitor," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "We are grateful to the patients, investigators, and other members of the clinical care teams for their contributions. Our team has been committed to rapidly advancing the development of Jaypirca for patients with MCL, and we look forward to building on this milestone by continuing to bring forward important new treatments for people with hematologic malignancies."

The FDA approval is based on data from a subset of patients in the BRUIN Phase I/II trial. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Patients with active central nervous system lymphoma or allogeneic hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days were excluded. Patients had received a median of three prior lines of therapy (range: 1 to 9), with 93% having two or more prior lines; all patients received one or more prior lines of therapy containing a covalent BTK inhibitor. Eighty-three percent (83%) of patients discontinued their last BTK inhibitor due to refractory or progressive disease. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an independent review committee (IRC) using 2014 Lugano criteria.

Results : Overall Response (ORR) 95% Cl (PET-CT scans were utliised in response assessments in 41% of patients and remainder by CT scans only) Jaypirca 200 mg,once daily (N=120):N= 60 (50%)(41.59).Complete Response (CR) (N=15)(13%). Partial Response (PR) (N= 45) (38%).Time to Median Response 1.8 months (0.8,4.2).Duration of Response Number censored 36.Median DOR months 8.3 (95% Cl) (5.7 NE). DOR rate at 6 months (95% Cl) 65.3 (49.8,77.1).

The pooled safety analysis of the full BRUIN study population evaluated 583 patients with hematologic malignancies administered Jaypirca 200 mg daily as a single agent. In this pooled safety population, the most common adverse reactions (ARs) to Jaypirca therapy, occurring in 20% of patients or more, were decreased neutrophil count, decreased hemoglobin, decreased platelet count, fatigue, musculoskeletal pain, decreased lymphocyte count, bruising, and diarrhea. The safety of Jaypirca was evaluated in 128 patients with MCL, 36% of whom were exposed for six months or longer and 10% of whom were exposed for at least one year. ARs led to dosage reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs that resulted in permanent discontinuation of Jaypirca in more than 1% of patients included pneumonia. Serious ARs occurred in 38% of patients who received Jaypirca. Serious ARs occurring in greater than or equal to 2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%).

"Until now, people living with MCL who can no longer be treated with BTK inhibitors have had few alternatives," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. "The approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.".