Bristol-Myers Squibb drops phase 3 trials of $800M IDO drug

Bristol-Myers is still enrolling patients in seven phase 1 and 2 trials featuring IDO1 inhibitor BMS-986205. (Bristol-Myers Squibb)

Bristol-Myers Squibb has pulled two phase 3 clinical trials of the IDO1 inhibitor it acquired through an $800 million takeover of Flexus. The studies are the latest dominoes to fall following the failure of Incyte’s rival IDO drug to move the needle in a pivotal trial.

Enrollment in the phase 3 trials of Bristol-Myers’ IDO1 drug BMS-986205 and cornerstone checkpoint inhibitor Opdivo in patients with non-small cell lung cancer or head and neck cancer was just getting started when news of Incyte’s setback hit less than four weeks ago. The Incyte data triggered a rapid re-evaluation of the IDO field, causing first NewLink and now Bristol-Myers to reconsider their strategies.

The rethink led Bristol-Myers to halt the trials after recruiting just one of the 1,750 subjects it initially planned to enroll across the two studies. Bristol-Myers listed “business objectives have changed” as the reason for canning the trials.

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Bristol-Myers has also effectively killed a phase 3 trial of the IDO1-PD-1 combination as a first-line treatment of patients with metastatic or unresectable melanoma, the same indication targeted in the Incyte study. The trial is active but has stopped enrollment well short of its target. Bristol-Myers had planned to enroll 700 patients, but recruitment stopped with 72 subjects on board. 

The actions wipe out Bristol-Myers’ near-term chances of establishing BMS-986205 as an essential add-on to Opdivo in some critical indications for its immuno-oncology franchise. But they fall short of completely killing off the asset.

“[Bristol-Myers] remains committed to continued research of BMS-986205-based combinations in an informed and scientifically robust manner,” a spokesperson said. “Insights from the evolving treatment landscape have brought to light the importance of better understanding the biological effects of the molecule, and identifying relevant biomarkers capable of selecting patient populations most likely to benefit from treatment. Therefore, it remains a priority to study BMS-986205-based combinations in the same and additional tumor types in early phase studies.”

RELATED: Body blow for Incyte as Merck-partnered melanoma trial bombs

With that in mind, Bristol-Myers is still enrolling patients in seven phase 1 and 2 trials featuring BMS-986205, including a study of the IDO1 drug in combination with Opdivo—and, in some cases, Yervoy—in 907 patients with advanced tumors. Four other trials featuring BMS-986205 are enrolling 200 to 500 patients. These studies also feature LAG-3 candidate relatlimab and a clutch of Bristol-Myers’ established oncology products. 

There remains scope for IDO inhibitors in development at Bristol-Myers and elsewhere to take flight again once researchers have a clearer understanding of why Incyte’s epacadostat study failed. 

Interest in IDO is underpinned by extensive research into the target’s role in immunosuppression, suggesting the core concept of targeting the pathway remains sound despite the pivotal trial failure. The question is whether better patient stratification or dosing refinements can breathe new life into the first wave of IDO drugs, or if researchers need to go back to the drawing board and find new ways to interfere with the pathway.