Eli Lilly oncology unit gets USFDA nod for Jaypirca to treat mantle cell lymphoma
MCL is a rare blood cancer and a form of non-Hodgkin lymphoma.
Indianapolis: Loxo@Lilly, the oncology unit of Eli Lilly and Company, has announced that the U.S. Food and Drug Administration (FDA) has approved Jaypirca (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase 1/2 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 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 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, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "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."
"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 1/2 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. Efficacy results are summarized below:
Outcome | Jaypirca 200 mg once daily (N=120) |
Overall Response Ratea,b | |
ORR, n (95% CI, %) | 60 (50 %) 41, 59 |
CR, n | 15 (13 %) |
PR, n | 45 (38 %) |
Time to Response Median (range), months |
1.8 (0.8, 4.2) |
Duration of Responsec | |
Number censored, n Median DOR, months (95% CI) DOR rate at 6 months, % (95% CI) | 36d 8.3 (5.7, NE) 65.3 (49.8, 77.1) |
a. PET-CT scans were utilized in response assessments (in 41% of patients), with the remainder being assessed by CT scans only.
b. ORR using CT scan-based assessments in all patients was 48% (95% CI: 38, 57), and CR rate was 13%.
c. Based on Kaplan-Meier estimation. Estimated median follow-up was 7.3 months.
d. Thirty-six (36) of 60 responders had not progressed or died prior to data cutoff.
"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.
