Lilly's Jaypirca blazes leukemia trail with FDA nod, fast confirmatory trial filing

As AbbVie, Johnson & Johnson, AstraZeneca and BeiGene are battling it out in the same BTK inhibitor market, Eli Lilly is trailblazing a new path for the blood cancer drug class.

On Friday, Dec.1, the FDA granted accelerated approval to Lilly’s Jaypirca for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy. Jaypirca, which is itself a BTK inhibitor, is now allowed following treatment with a BTK inhibitor and a BCL-2 inhibitor.

The ability to help patients who have failed on a BTK inhibitor makes Jaypirca unique. The Lilly med is a non-covalent BTK inhibitor that binds to BTK by a mechanism different from existing covalent agents, namely AbbVie/J&J’s Imbruvica, AZ’s Calquence and BeiGene’s Brukinsa.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, M.D., Ph.D., the CLL section head at The University of Texas MD Anderson Cancer Center, said in a statement Friday.

Still, the FDA's speedy approval isn’t the most ideal. According to past disclosures, Lilly sought after an accelerated approval in the third line based on tumor shrinkage data from the single-arm BRUIN phase 1/2 trial, even though the trial included patients who had gotten a BTK but not a BCL-2 inhibitor such as AbbVie and Roche’s Venclexta.

The updated Jaypirca label now shows that the drug shrank tumors in 78% of 108 patients previously treated with both a BTK and a BCL-2 inhibitor, with the response lasting a median 12.2 months. At last year’s American Society for Hematology annual meeting in December, data from the BRUIN trial linked Jaypirca to an overall response rate of 79% among 100 BTK/BCL-2 takers and 82.2% among 247 prior BTK patients.

All FDA accelerated approvals come with requirements for further evidence to confirm the drug’s clinical benefit. Alongside the Jaypirca approval, Lilly said the phase 3 confirmatory trial, BRUIN CLL-321, has already hit its primary endpoint of progression-free survival, and the results were shared with the FDA in November.

The BRUIN CLL-321 data haven’t been publicly shared or formally reviewed by the FDA. The trial tested Jaypirca in BTK-pretreated CLL/SLL patients with or without prior exposure to BCL-2. The Lilly drug was pitted against physician’s choice of either the combination of Gilead’s PI3K inhibitor Zydelig and rituximab or the bendamustine-rituximab pairing.

A separate trial, BRUIN CLL-322, is adding Jaypirca to Venclexta and rituximab in previously treated CLL/SLL. These patients’ prior treatments may or may not include a BTK inhibitor. While the current Jaypirca regimen gives the drug until disease progression or unacceptable toxicity, the BRUIN CLL-322 trial stops Jaypirca after a limited time.

In addition, Lilly’s BRUIN CLL-313 study is comparing Jaypirca versus the bendamustine-rituximab combo in untreated CLL/SLL patients.

Frontline CLL is the most important battleground for covalent BTK inhibitors. But Jake Van Naarden, CEO of Lilly’s oncology unit Loxo, previously told Fierce Biotech that BTK-experienced CLL represents the “core value proposition” of Jaypirca.

Post-covalent BTK is still a sizeable market for Jaypirca because the BTK inhibitors are not curative and most patients will need additional treatment, Van Naarden explained.

The three covalent options are currently duking it out in frontline CLL, with Imbruvica losing share. In the third quarter of 2023, BeiGene saw Brukinsa sales jump 150% year over year to $270 million in the U.S. AZ’s Calquence sales increased by 2% to $468 million in the U.S. in Q3. In the meantime, AbbVie recorded a 20% decline for Imbruvica’s U.S. revenue to $678 million.

Jaypirca got its initial FDA nod in January as a third-line, post-BTK mantle cell lymphoma treatment. With that limited indication, Jaypirca brought in $22.7 million sales in Q3. The confirmatory trial for that accelerated approval, BRUIN MCL-321, is pitting Jaypirca against investigator’s choice of Imbruvica, Calquence or Brukinsa in MCL patients who have tried at least one prior line of therapy.