FDA Approves Jaypirca for Leukemia/Lymphoma Indication

The FDA has granted accelerated approval of Lilly’s Jaypirca (pirtobrutinib) to treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). It is indicated for those who have received at least two prior lines of therapy.

Both cancers are slow-growing forms of non-Hodgkin lymphoma that develop from white blood cells. Chronic lymphocytic leukemia is one of the most common types of leukemia in adults. In the United States, CLL accounts for about one-quarter of the new cases of leukemia and there are about 18,740 new cases of CLL diagnosed this year. Small lymphocytic lymphoma is a similar cancer. In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.

Jaypirca is a non-covalent kinase inhibitor and uses a novel binding mechanism to target the specific mutations associated with resistance. It is able reestablish Brutons tyrosine kinase (BTK) inhibition in patients. Brutons tyrosine kinase is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma.

When it first launched early in 2023, Jayprica had U.S. wholesale acquisition cost of $21,000 per 30 days of therapy for the 200 mg dose per day. Jayprica has also been granted accelerated approval to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), a rare blood cancer and a form of non-Hodgkin lymphoma (NHL).

Related: FDA Approves Lilly’s BTK Inhibitor for Rare Blood Cancer

Brian Koffman, M.D.

“The treatment landscape for CLL has been dramatically improved by the introduction of covalent BTK inhibitors and BCL-2 inhibitors. However, most patients will unfortunately relapse eventually,” Brian Koffman, M.D., chief medical officer and executive vice president at the CLL Society, said in a press release. “Pirtobrutinib’s approval gives patients a much-needed option and brings forward new possibilities as they continue their treatment journey.”

The approval for the CLL/SLL indication was under the FDA’s accelerated approval pathway based on overall response rate (ORR) and duration of response (DOR) from the open-label, single-arm phase 1/2 BRUIN trial. The assessment of efficacy was based on 108 patients with CLL/SLL treated with Jaypirca 200 mg, which was given once daily and was continued until disease progression or unacceptable toxicity. The overall response rate was 72% and the duration of response was 12.2 months.

The safety of Jaypirca was evaluated in 110 patients with CLL/SLL. Adverse events led to dose reductions in 3.6% of patients, treatment interruption in 42% of patients, and permanent discontinuation of Jaypirca in 9% of patients. Serious adverse events occurred in 56% of patients who received Jaypirca. These include pneumonia, COVID-19, sepsis, and febrile neutropenia.

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

The phase 3 randomized confirmatory trial intended to convert this approval to traditional approval is BRUIN CLL-321, which reached its target number of progression-free survival (PFS) events and met its primary endpoint. Data are being presented at the upcoming American Society of Hematology (ASH) Annual Meeting and Exposition taking place Dec. 9, 2023, to Dec. 12, 2023, in San Diego.