Bristol-Myers Squibb's Next Big Bet After Opdivo Failure—IDOs
April 4, 2017
By Alex Keown, BioSpace.com Breaking News Staff
NEW YORK – On Sunday, Bristol-Myers Squibb and Incyte forged a deal to evaluate the combination of epacadostat and Opdivo as a first-line therapy for non-small cell lung cancer across the spectrum of PD-L1 expression and first-line treatment for head and neck cancer.
The two drugs will enter two Phase III trials in lung cancer and add cohorts to an ongoing Phase I/II melanoma study, the companies said.
Epacadostat is an investigational oral selective IDO1 enzyme inhibitor. The drug is designed to modulate anti-tumor immune responses through the promotion of regulatory T cell generation. The drug also blocks effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance, according to company information. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma, the company said.
BMS’ Opdivo (nivolumab) is Bristol-Myers PD-1 immune checkpoint inhibitor, a drug that has had some recent troubles. In August 2016, Opdivo failed to meet its endpoints in a Phase III trial as a monotherapy for a “broad patient population” in patients with previously untreated advanced non-small cell lung cancer. In March 2015, Opdivo was approved for treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Opdivo is an immuno-therapy drug delivered via injection that harnesses the patient’s own immune system to fight cancerous cells. It was the first PD-1 inhibitor to receive regulatory approval.
While BMS is pairing with Incyte’s IDO, the company is also developing its own in-house IDO therapy. Earlier this week, the company presented an abstract at the American Association for Cancer Research annual meeting showing off its IDO1 inhibitor, BMS-986205. Endpoints reported that evidence of substantial serum kyn reduction was observed in various dosed by patients taking BMS-986205. Fouad Namouni, BMS’s head of oncology development, told Endpoints that the company’s IDO “has the potential to be one of the most potent in the class.”
BMS isn’t the only company to partner with Incyte on a combination therapy using epacadostat. Earlier this year, Merck & Co. struck a deal to pair epacadostat with its anti-PD-1 therapy, Keytruda. The two companies will explore the combination across five tumor types: metastatic melanoma, non-small cell lung cancer (NSCLC), bladder cancer, renal cell carcinoma (RCC), and squamous cell carcinoma of the head and neck (SCCHN).
Incyte also has partnerships with Roche and its drug, Tecentriq, and AstraZeneca ’s durvalumab. Since Opdivo crashed and burned in that late summer trial, Keytruda and Tecentriq have gained market share over Opdivo.