Cancer associated fibroblasts layer on tumor microenvironment
3D rendering of cancer-associated fibroblasts CAF layer on tumor microenvironment.[Marcin Klapczynski/Getty Images]

The U.S. FDA has approved Jaypirca (pirtobrutinib) for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have had at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor. Jaypirca is the first and only FDA approved non-covalent (reversible) BTK inhibitor. It can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and thus extends the benefit of targeting this pathway.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor,” said Michael Wang, MD, Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center.

FDA approved BTK inhibitors include AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence, and BeiGene’s Brukinsa. All three products are covalent BTK inhibitors that can’t be used sequentially. Because Jaypirca binds to BTK differently, it can be used in patients who progress on another BTK inhibitor, which many patients do.

Wang added, “These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy. Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Jaypirca’s labeling contains warnings 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.

The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial, results of which appeared in The Lancet in 2021. The efficacy assessment was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Jaypirca was approved under the FDA’s Accelerated Approval pathway. The confirmatory Phase III trial (NCT04662255; BRUIN MCL-321) is currently enrolling patients.

“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.”

Jaypirca is expected to be available in the United States in the coming weeks.

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