Lilly breaks new ground for BTK class with Jaypirca approval

Eli Lilly has picked up an FDA approval for its non-covalent BTK inhibitor Jaypirca in relapsed mantle cell lymphoma (MCL) patients who relapse after treatment with current drugs in the class. The accelerated approval covers adult MCL patients who have previously been treated with at least two lines of systemic therapy, including a covalent BTK inhibitor. Jaypirca (pirtobrutinib) has been specifically designed to work in patients who develop resistance mutations to current BTK inhibitors for MCL, such as AbbVie/Johnson & Johnson's Imbruvica (ibrutinib), AstraZeneca's Calquence (acalabrutinib), and BeiGene's Brukinsa (zanubrutinib). It is the first non-covalent or reversible BTK drug to be cleared by the FDA, and targets a different binding site on the BTK protein for its mechanism of action. In the open-label, phase 1/2 BRUIN clinical trial, which included 120 patients with MCL, as well as patients with other forms of blood cancer, Jaypirca at an oral dose of 200 mg once a day had an objective response rate of 50%, including 13% complete responses, and a median duration of response of more than eight months. Patients in the study had been treated with a median of three prior lines of therapy, including at least one covalent BTK inhibitor. "Until now, people living with MCL who can no longer be treated with BTK inhibitors have had few alternatives," commented Meghan Gutierrez, chief executive of the Lymphoma Research Foundation in the US. "The approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL," she added. MCL is pretty rare, but this first FDA approval raises expectations that Lilly could also get a green light for Jaypirca in other indications, like chronic lymphoblastic leukaemia (CLL) and small lymphocytic leukaemia (CLL), which cover a much larger patient population. At last year's ASH congress, results from the CLL cohort in BRUIN showed that Jaypirca achieved a stellar ORR of more than 82% in patients previously treated with a BTK drug, and 79% in patients previously-treated with Abbvie's BCL-2 inhibitor Venclexta (venetoclax), another important therapy for MCL. Continued approval in MCL, meanwhile, is likely to depend on the outcome of confirmatory clinical trials. Lilly is running a phase 3 trial called BRUIN MCL-321, which is comparing Jaypirca to physician's choice of BTK inhibitors in MCL patients who have received one or more prior lines of therapy and are BTK inhibitor naïve. Lilly said Jaypirca is expected to be available in the US "in the coming weeks", which has set a list price of $21,000 for a 30-day supply of the drug, a premium to the covalent BTK drugs, which typically cost between $13,000 and $16,000 per month.