FDA approves pirtobrutinib for the treatment of advanced relapsed/refractory mantle cell lymphoma

February 2023 Pharma News Andrea Enguita

The FDA has granted accelerated approval to Jaypirca™ (pirtobrutinib) for the treatment of patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) who received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. This decision is based on the results of the phase 1/2 BRUIN trial and represents an important advance for patients with R/R MCL, who currently have a poor prognosis.

Mantle cell lymphoma (MCL) is a form of non-Hodgkin lymphoma (NHL) that arises in B lymphocytes, frequently in those located in the mantle zone of the outer edge of lymph nodes. Patients with relapsed/refractory (R/R) MCL have a poor prognosis after treatment discontinuation with a covalent Bruton tyrosine kinase (BTK) inhibitor. Pirtobrutinib is a highly selective, non-covalent (reversible) BTK inhibitor. In fact, pirtobrutinib is 300 times more selective for BTK than 98% of other kinases tested in preclinical studies. The BRUIN phase 1/2 clinical trial is the ongoing first-in-human evaluation of pirtobrutinib in patients with haematologic malignancies, MCL. Jaypirca was approved under the FDA’s Accelerated Approval pathway based on response rate results from this trial.

Study findings

The FDA approval was based on data from a subset of patients of the BRUIN phase 1/2 trial. This subset consisted of 120 patients with R/R MCL who were treated with pirtobrutinib at a dose of 200 mg once daily until disease progression or unacceptable toxicity. Patients in this cohort had received a median of three (range, 1-9) prior lines of therapy. All patients received one or more prior lines of therapy containing a covalent BTK inhibitor.

Researchers reported a 50% overall response rate, with 13% of patients achieving a complete response. Time to response was 1.8 months, with a median duration of response (DOR) of 8.3 months. At six months, the DOR rate was reported at 65.3%. A safety analysis was performed on a population of 128 patients, of whom 36% received the study drug for at least six months (10% at least one year). Adverse events led to dosage reductions in 4.7% of patients, treatment interruption in 32%, and permanent discontinuation in 9%. Serious adverse reactions occurred in 38% of patients, the most common of which included pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), haemorrhage (2.3%), pleural effusion (2.3%) and sepsis (2.3%).

Pirtobrutinib is the first BTK inhibitor of any kind specifically approved for the treatment of patients with MCL who previously treated with a covalent BTK inhibitor. This approval brings new hope to patients with R/R MCL, who, up to now, had very limited options and a poor prognosis.


U.S. FDA Approves Jaypirca™ (pirtobrutinib), 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. Press release. 27th January, 2023.