FDA Approves Lilly’s BTK Inhibitor for Rare Blood Cancer

The FDA has granted accelerated approval to Lilly’s Jaypirca (pirtobrutinib) to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), a rare blood cancer and a form of non-Hodgkin lymphoma (NHL). Annually, about one in 200,000 people worldwide develop MCL.

The U.S. wholesale acquisition cost of Jaypirca is $21,000 per 30 days of therapy for the 200 mg dose per day. Jaypirca is expected to be available in the United States in the coming weeks.

A Lilly spokesperson said that because oncology is a protected class, they anticipate Medicare Part D plans to add Jaypirca to their formularies within 90 days. “We will work closely with our payer customers to secure access for patients,” the spokesperson said.

The use of covalent Bruton’s tyrosine kinase (BTK) inhibitors — such as Imbruvica (ibrutinib), Calquence (acalabrutinib), or Brukinsa (zanubrutinib) — provides a chemotherapy-free option for patients with mantle cell lymphoma. But patients can become resistant to therapy because of mutations in BTK.

Developed by Lilly’s oncology unit, Loxo@Lilly, Jaypirca is a non-covalent, highly selective kinase inhibitor and uses a novel binding mechanism to target the specific mutations associated with resistance. It can reestablish BTK inhibition in patients with mantle cell lymphoma who have previously been treated with a covalent BTK inhibitor.

Michael Wang, M.D.

“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,” Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, said in a press release. “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.”

The accelerated approval was based on response rate from an open-label, single-arm, phase 1/2 study. In the BRUIN trial, Jaypirca-treated patients with relapsed or refractory MCL who had been treated previously with a covalent BTK inhibitor achieved an overall response rate of 50%, with 13% of patients achieving a complete response. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. In the study, 83% of patients discontinued their last BTK inhibitor due to refractory or progressive disease.

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. The most common adverse reactions 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.

In the 128 patients with MCL, adverse reactions led to dosage reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Serious adverse reactions occurred in 38% of patients who received Jaypirca.