Eli Lilly has officially given up ex-China rights to Innovent Biologics’ Tyvyt, a PD-1 inhibitor that was once billed as a potential low-cost choice in a multibillion-dollar class. The drug was also the poster child in a group of China-developed medicines that drew Big Pharma interest.
Lilly terminated the Tyvyt deal covering geographies outside of China and kicked the drug back to Innovent in October, the Indianapolis pharma said in its third-quarter securities filing.
The drug, also called sintilimab, was the protagonist in a high-profile FDA rejection back in March. At that time, the FDA turned down Tyvyt’s application in newly diagnosed nonsquamous non-small cell lung cancer (NSCLC) and castigated the partners for using China-only pivotal data that compared the experimental therapy to an outdated regimen.
Tyvyt’s fate in the U.S. was pretty much set in stone after that rebuff. In its previous quarterly report (PDF) filed in August, Lilly said it didn’t plan to pursue an FDA submission. At the time, it wasn’t clear whether Lilly’s statement applied to all potential indications or just the NSCLC use.
Lilly first teamed with Innovent on cancer medicines in China in 2015. As part of that strategic partnership, Tyvyt won its first Chinese approval in classical Hodgkin lymphoma in December 2018. Then in 2020, Lilly paid $200 million upfront and committed up to $825 million in potential milestones to gain exclusive ex-China rights to Tyvyt. Without an FDA approval, Lilly essentially spent $200 million for nothing but an FDA slap-down, and Innovent didn’t get a penny of the potential milestone.
Lilly’s decision to exit the ex-China part of the Tyvyt deal also comes a year after the U.S. pharma narrowed the original China pact. Beginning 2022, Lilly took a back seat on Tyvyt in China, offering distribution service and development advice while handing some sales detailing responsibilities to Innovent. The move came as the Chinese PD-1/L1 market started to become overly competitive. In the first nine months of 2022, Lilly recorded $236 million Tyvyt sales in China, down from $340 million during the same period last year.
Shortly after Lilly called it quits on Tyvyt, EQRx in November decided it wouldn't pursue a U.S. approval for CStone Pharmaceuticals’ China-made PD-L1 inhibitor sugemalimab in metastatic NSCLC after seeing “no commercially viable path.” Similar to Tyvyt, sugemalimab also has China-only pivotal data comparing its combination with chemo against chemo alone, while the FDA now wants a global trial against U.S.-approved PD-1 agents.
Both Lilly and EQRx have openly indicated that they would offer their meds at lower list prices than existing PD-1 inhibitors. Lilly, for its part, promised a 40% discount for Tyvyt right before its damning FDA advisory committee meeting.
Some industry watchers have lamented the FDA’s newly adopted attitude toward cancer drugs with China-only data, saying it nixed a chance to disrupt the market filled with several options that all carry similarly high prices.
But the FDA’s oncology chief Richard Pazdur, M.D., argued the agency’s rejection of Tyvyt and of single-country data are in everybody’s “long-term interests.” To Pazdur, it’s important to set the record straight on how cancer drug development should be done. He also questioned the motive of ex-U.S. single-country trials during Friends of Cancer Research’s annual meeting a few days ago, suggesting companies are running them to avoid putting their therapies against the most updated standard of care.
With Tyvyt and sugemalimab now dead in the water, several other China-made PD-1 inhibitors and their U.S. partners are still plowing ahead. BeiGene and Novartis’ tislelizumab is waiting for an FDA verdict in previously treated esophageal squamous cell carcinoma, and Junshi Biosciences and Coherus Biosciences have a resubmission for toripalimab in nasopharyngeal carcinoma. Both decisions are now delayed because COVID-related travel restrictions have prevented the FDA from performing plant inspections in China.
In addition, Arcus Biosciences is working on PD-1 antibody zimberelimab, which it in-licensed from WuXi Biologics and Gloria Pharmaceuticals. Arcus and partner Gilead Sciences just recently adjusted the design of a phase 3 NSCLC trial to compare a combination of zimberelimab and anti-TIGIT domvanalimab directly against Merck’s PD-1 king Keytruda instead of chemotherapy.