With FDA approval for Jaypirca, Eli Lilly introduces new BTK blood cancer drug

A fourth BTK inhibitor for blood cancer treatment has arrived—but this one is different than the others.

Eli Lilly has won an FDA accelerated approval for pirtobrutinib for mantle cell lymphoma (MCL) after at least two prior lines of therapy, including a BTK inhibitor, the company said Friday.

The drug will be made available in the U.S. in the coming weeks under the brand name Jaypirca, Lilly said. The Indianapolis pharma is offering Jaypirca at a list price of $21,000 for a 30-day supply, a Lilly spokesperson told Fierce Pharma.

Before Jaypirca, the FDA already approved three BTK inhibitors—AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa. But Jaypirca is different from those products, and Lilly is mainly angling its drug at a different market, Jake Van Naarden, CEO of Lilly’s oncology unit Loxo, said in a November interview.

While the three earlier products are covalent BTK inhibitors that can’t be used sequentially, Jaypirca is a non-covalent BTK inhibitor. Jaypirca binds to BTK differently and therefore can be used after progression on another BTK inhibitor. This mechanism gives Jaypirca a unique opportunity to treat patients who have failed on another BTK inhibitor, and most blood cancer patients eventually do progress on covalent BTK.

Lilly sees “a real opportunity” for Jaypirca to treat patients following failure of one of those current BTK durgs, Van Naarden said.

“Over time, physicians may want to use the drug in the first line. That’s great,” Van Naarden said. “That’s not the core value proposition of the drug.”

Jaypirca won its FDA go-ahead based on tumor shrinkage data from the phase 1/2 BRUIN trial. In a group of covalent BTK-pretreated MCL patients, Jaypirca, given at 200 mg once daily, recorded an overall response rate of 50% and completely cleared signs of tumor in 13% of patients. The responses lasted for a median 8.3 months.

The current go-ahead is an accelerated approval, meaning Lilly is on the hook to verify Jaypirca’s clinical benefit. The ongoing phase 3 BRUIN MCL-321 trial serves as the confirmatory study, according to Lilly. The trial is comparing Jaypirca with investigator’s choice of Imbruvica, Calquence or Brukinsa in MCL patients who have received at least one prior line of therapy but are new to a BTK inhibitor.

While all four BTK inhibitors have won their initial approvals in MCL, the chronic lymphocytic leukemia (CLL) use matters more for members of the drug class. And Jaypirca already has some data there. In the same phase 1/2 BRUIN trial, Jaypirca shrank tumors in 82.2% of a group of BTK-pretreated CLL patients, according to data presented at ASH 2022.

Lilly is discussing the CLL data with the FDA but is not ready to comment on any potential regulatory plans, the company spokesperson said.

Jaypirca’s approval marks a boost for Lilly’s oncology business after the embarrassing FDA rejection of then Innovent Biologics-partnered PD-1 inhibitor Tyvyt (sintilimab) last year. It also follows a surprising FDA rejection of closely watched Alzheimer’s disease drug donanemab last week.