The second shoe has dropped in Eli Lilly and Innovent Biologics’ effort to bring a cancer treatment developed in China to the US market.
The two businesses said Thursday that the FDA has rejected the PD-1 inhibitor sintilimab (Tyvyt in China) in newly diagnosed nonsquamous non-small cell lung cancer. The comprehensive response letter follows the FDA’s and an external expert panel’s highly unfavourable evaluations.
In keeping with the FDA’s previous stance on the application, the agency proposes that the partners conduct an additional worldwide clinical study. According to the FDA, the current trial should demonstrate that the combination of Tyvyt and chemotherapy works at least as well as standard of care in terms of prolonging patients’ lives.
According to the statement, Lilly and Innovent are “evaluating future actions for the sintilimab initiative in the United States.”
Lilly and Innovent utilised the phase 3 ORIENT-11 study, which was only done in China, for Tyvyt’s application. The Tyvyt-chemo combination was compared to chemo alone in Chinese patients with newly diagnosed nonsquamous NSCLC. As its primary aim, the study employed the progression-free survival marker, which measures how well a medication can halt tumour progression or mortality.
Tyvyt’s fate was spelled out for it in hindsight when Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, penned an article in The New England Journal of Medicine in December questioning the use of clinical data generated solely or predominantly in China to seek U.S. approvals.
The FDA scolded Lilly and Innovent for losing sight of trial variety, echoing Pazdur’s piece and a subsequent Lancet Oncology article. The FDA also criticised the study’s comparison arm and trial design, pointing out that PD-1 treatment has already established the standard of care in the United States after demonstrating a life-extension benefit over chemotherapy on the gold-standard overall survival measure.
Adding another twist to the process, Lilly said on the day of a scheduled FDA advisory committee meeting in February that if Tyvyt is authorised, it will be priced at a 40 percent reduction over current PD-1s. The strategy plainly failed, given the FDA does not consider drug pricing in its evaluations.
The FDA’s oncology experts ultimately voted 14-1 against approval in its present form, instead requesting that Lilly and Innovent conduct a new clinical trial. The lone “no” vote was made by Jorge Nieva, M.D., of the University of Southern California, who did point out that the availability of so-called “me-too” medications might bring down costs.
Meanwhile, several PD-1/L1 inhibitors produced in China with possibly reduced price tags are lined up at the FDA’s door. Some intended to join the lucrative U.S. market with China-only data after Pazdur basically advocated such a strategy during a gathering of the American Association for Cancer Research in 2019.
Coherus Biosciences and Junshi Biosciences are awaiting an FDA ruling on toripalimab, a PD-1 inhibitor authorised in China, for nasopharyngeal cancer. The application is likewise based only on data from China, although the disease’s rarity and prevalence in Asian populations may qualify the medicine for what the FDA calls “regulatory flexibility.”
Furthermore, the FDA’s additional criteria, such as comparing a latecomer to an established PD-1 in front-line NSCLC, have generated concerns about a large portfolio of candidates, according to SVB Leerink analyst Daina Graybosch, Ph.D.
The FDA’s rejection represents a blow for Lilly’s growing cancer portfolio. Innovent, on the other hand, is reliant on getting into the US market to continue growth.
“Throughout the registrational process, the company has gained tremendous experience and know-how, and established a strong registration team, allowing the company to be more confident and committed to bringing our innovative drugs to global markets through a defined pathway,” Innovent said in a statement.