The world’s first injectable immune checkpoint inhibitor likely won’t make it to the U.S. anytime soon after the China-approved drug flunked a pivotal trial in a rare cancer, forcing its stateside developer Tracon Pharmaceuticals to explore strategic alternatives.
The drug, a subcutaneous PD-L1 inhibitor called envafolimab, only triggered responses in four out of 82 patients, or 5%, who had already received therapies for their undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS), which affect the soft tissues of the body. The number was below the 11% the phase 2 trial was targeting as its primary endpoint.
Tracon said it’s scrapping further development of envafolimab altogether, as an application with the FDA is out of the question. That means another cohort of the study, which was examining envafolimab in combination with Bristol Myers Squibb’s CTLA4 inhibitor Yervoy, will not go on to see any results.
The San Diego firm is now moving to “immediately reduce cash burn,” CEO Charles Theuer, M.D., Ph.D., said in a statement. The company will focus entirely on seeking strategic alternatives, which may include “a merger, reverse merger, acquisition, other business combination, sales of assets, licensing or other strategic transactions,” it said.
During that search, Tracon said it plans to leverage its in-house drug development capabilities that have been used to conduct more than 15 oncology trials over 12 years. Still, the process may yield no satisfactory results, and Tracon warned Monday that the firm may eventually have to close up shop.
As of the end of 2023, the small biotech had 17 full-time employees, according to its annual securities filing.
It marked a dramatic turn of events for what was the first subcutaneous checkpoint inhibitor approved anywhere in the world. Envafolimab claimed that title in 2021 with a Chinese approval in advanced microsatellite instability-high or mismatch repair-deficient solid tumors regardless of their location in the body. The tumor-agnostic nod was based on results from a pivotal phase 2 trial conducted in China.
Tracon in-licensed the North America rights to envafolimab in December 2019 through an agreement with the drug’s Chinese developers, 3D Medicines and Alphamab Oncology.
Given the many approvals for PD-1/L1 inhibitors such as Merck’s Keytruda in the U.S., Tracon picked the niche soft-tissue sarcoma indication for envafolimab’s initial label. But, now, the drug’s overall response was apparently no better than the 4% rate previously recorded by Novartis’ Votrient, which is the only FDA-approved treatment for refractory UPS or MFS.
The envafolimab flop is also another major blow to Alphamab, which, about a month ago, said its investigational PD-L1/CTLA-4 bispecific antibody, dubbed KN046, failed to move the needle in a phase 3 trial in pancreatic cancer.
Without contributions from the U.S., Alphamab will likely have a hard time relying solely on the Chinese market. Sold under the brand name Enweida, envafolimab generated revenue of roughly 196 million Chinese yuan ($27 million) for Alphamab in 2023.
Chinese authorities have approved nearly 20 PD-1/L1 inhibitors, including one green light last week. So going abroad, especially to the U.S., has become one way for China-made checkpoint inhibitors to have a better life. But not all those efforts have been successful.
In 2022, the FDA rejected Innovent Biologics’ PD-1 inhibitor Tyvyt, then partnered with Eli Lilly, which later returned the drug’s U.S. rights. The agency recently also snubbed Jiangsu Hengrui Pharma and Elevar Therapeutics’ camrelizumab, used in combination with the VEGFR inhibitor rivoceranib, because of problems related to the FDA’s inspections of manufacturing and clinical trial sites.
So far, Junshi Biosciences’ Coherus BioSciences-partnered Loqtorzi and BeiGene’s Tevimbra have secured FDA approvals, although the latter has not been commercially launched.