In a less-than-ringing endorsement, FDA advisers voted Wednesday 6-5 in favor of approving Eli Lilly’s Cyramza plus Roche’s Tarceva in previously untreated EGFR-positive non-small cell lung cancer (NSCLC). And the advisory committee’s narrow approval could foreshadow the challenges Lilly will face in what has become a super-competitive market.
The FDA doesn’t have to follow the advice of its advisory committees, but it usually does, setting Cyramza up for its sixth FDA approval. But an OK would also set Lilly on a collision course with AstraZeneca, which dominates the EGFR lung cancer market with its blockbuster Tagrisso.
The FDA advisers based their recommendation on Lilly’s Relay trial, in which it reported that adding Cyramza to Tarceva reduced the risk of disease progression or death by 40% over Tarceva alone. The combination also stalled tumor growth by 19.4 months compared with 12.4 months for Tarceva alone.
Before the FDA advisory committee meeting, Lilly provided updated survival data in response to a request from the advisers. As of Jan. 27, 53 patients were still on the treatment, Lilly reported, but it won’t be possible to determine overall survival until 2023, it said. It projected that survival times would be 58 months for the Cyramza combo versus 52 months for Tarceva plus placebo.
Lilly’s update stated that combining Cyramza with Tarceva did produce a “clinically meaningful improvement” in the amount of time patients lived without their disease worsening, as well as comparable safety to Tarceva alone and “no detriment in survival.”
But will that be enough to lure oncologists to the Cyramza combo? Given Tagrisso’s impressive data haul, that’s an open question.
Way back in 2017, AZ reported that Tagrisso alone kept lung cancer from progressing for a median 18.9 months, versus 10.2 months for Tarceva and AZ’s older drug Iressa. Then, last summer, AZ presented new data showing Tagrisso extended the lives of lung cancer patients by a median of 38.6 months, while older EGFR inhibitors posted survival gains of 31.8 months.
Wall Street analysts are so high on Tagrisso’s prospects that when AZ reported fourth-quarter sales of the product jumped 49% year over year to $884 million, they were actually disappointed.
Lilly, for its part, is optimistic about Cyramza’s prospects in EGFR-mutated NSCLC. "We believe in the clinical meaningfulness of the data from the Relay trial, which targeted the VEGFR and EGFR pathways together,” Maura Dickler, M.D., vice president of late-phase development for Lilly Oncology, said in a statement.
In the fourth quarter, sales of Cyramza grew 11% to $245 million, beating the Zacks consensus estimate of $206 million. Lilly reported an increase in demand for the drug in the U.S., and the company also won approval from the European Commission to expand the product’s label to include the Tarceva combo in EGFR-positive NSCLC.
Still, competition may not be Lilly’s only challenge, judging from AZ’s recent reimbursement hurdles. In January, England’s drug-cost watchdog National Institute for Health and Care Excellence rejected Tagrisso in EGFR-positive NSCLC, stating that there’s not enough evidence it’s any better than Boehringer Ingelheim’s Gilotrif. It made that decision despite being offered a confidential discount on Tagrisso from AZ.