Eli Lilly announced on Friday that the FDA has granted fast approval to pirtobrutinib for the treatment of mantle cell lymphoma (MCL) in patients who have progressed despite receiving at least two prior lines of therapy, one of which was a BTK inhibitor.
In light of last year’s embarrassing FDA rejection of Innovent Biologics and Lilly’s PD-1 inhibitor Tyvyt (sintilimab), this approval comes as welcome news for Lilly’s oncology business.
The company announced that the drug, which will be sold under the name Jaypirca, will soon be available in the U.S. According to a Lilly representative, the list price for a 30-day supply of Jaypirca at the Indianapolis pharmaceutical company is $21,000.
Jaypirca is the fourth BTK inhibitor for the treatment of blood cancer. Before it came around, the FDA had already given the nod to three others, namely AstraZeneca’s Calquence, BeiGene’s Brukinsa and AbbVie and Johnson & Johnson’s Imbruvica. However, the CEO of Lilly’s oncology unit, Loxo, Jake Van Naarden, claimed in an interview last November that Jaypirca is distinct from those treatments and is primarily targeted toward a different market.
Jaypirca is a non-covalent BTK inhibitor, whereas the three drugs that came before it are all covalent BTK inhibitors that can’t be used back-to-back. Since Jaypirca binds to BTK in a different way, it can be utilized once another BTK inhibitor has failed. Since most patients with blood cancer do ultimately progress on covalent BTK, this approach gives Jaypirca the unique potential to treat patients who have been unsuccessful on another BTK inhibitor.
Van Naarden noted that Lilly sees a significant possibility for Jaypirca to treat patients when one of the existing BTK drugs has failed. “Over time, physicians may want to use the drug in the first line. That’s great,” he said. “That’s not the core value proposition of the drug.”
Data showing that tumors shrank during the phase 1/2 BRUIN trial was crucial in getting Jaypirca approved by the FDA. With a once-daily dose of 200 mg, Jaypirca induced a 50% overall response rate and a full disappearance of tumor symptoms in 13% of covalent BTK-pretreated individuals with MCL. There was a mean retention of 8.3 months for the responses.
Given that the current approval is an accelerated one, the burden of proof for the clinical efficacy of Jaypirca falls on Lilly. The company claims that the current phase 3 BRUIN MCL-321 study can be viewed as a confirmatory study. Patients with MCL who have previously undergone at least one line of therapy but are unfamiliar with the BTK inhibitor are being asked to participate in a clinical trial comparing Jaypirca to the investigator’s choice of Calquence, Imbruvica or Brukinsa.
All four BTK inhibitors have received initial approval for treating MCL, but the chronic lymphocytic leukemia (CLL) market is far larger and more important overall. And Jaypirca has some data there already. The drug reduced tumor size in over 80% of BTK-pretreated CLL patients in the same phase of the trial.
Lilly is in discussions with the FDA regarding the CLL findings, but the company is not yet ready to comment on any prospective regulatory plans.