During an R&D Day presentation, Bristol Myers Squibb (BMS) made significant alterations to its development pipeline. The company announced that it will discontinue two mid-stage and four early-stage clinical programs due to concerns related to their efficacy and safety.
Among the programs being terminated are two Phase II clinical initiatives. One of these programs focused on an investigational asset designed to target heat shock protein 47 (HSP47) using small interfering RNA (siRNA). This asset was originally licensed from Nitto Denko in 2016, with BMS making an upfront payment of $100 million. The objective of the siRNA compound was to diminish the presence of heat shock protein, a protein linked to the excessive buildup of collagen, a key characteristic of nonalcoholic steatohepatitis (NASH), the most severe variant of fatty liver disease. In 2019, BMS carried out a Phase II clinical trial, evaluating two distinct dosages of the siRNA in a group of 61 patients who had developed scar tissue due to hepatitis C infection.
Unfortunately, neither dosage demonstrated superior effectiveness compared to a placebo in inhibiting liver scarring, as indicated by data in the federal clinical trials database.
BMS’s decision to discontinue the siRNA program comes shortly after Madrigal Pharmaceuticals announced that its NASH treatment, resmetirom, had received priority review status from the FDA. The FDA’s decision on resmetirom is expected by March 14, 2024. Madrigal’s stock experienced a substantial increase of over 200% in December following positive results in a Phase III trial, where the drug met both primary and secondary endpoints.
BMS disclosed the discontinuation of an early-stage anti-TIGIT solid tumor program that was investigating the efficacy of an antibody in treating non-small cell lung cancer (NSCLC). NSCLC typically exhibits lower responsiveness to chemotherapy and radiation therapy in comparison to small cell lung cancer, as outlined by information from the National Cancer Institute. Nevertheless, the clinical trial came to a halt after enrolling just one patient, with Bristol-Myers Squibb (BMS) citing “safety concerns and an adverse shift in the risk-to-benefit ratio,” as reported in the federal clinical trials database. Despite this setback, BMS is continuing to advance an early-stage bispecific anti-TIGIT program that it acquired from Agenus in 2021.
This agreement involved an upfront payment of $200 million and the potential for milestone payments of up to $1.36 billion.
The field of anti-TIGIT drugs encountered setbacks in May 2022 when Roche’s Genentech reported disappointing Phase III results, raising doubts about other companies’ efforts to develop similar drugs. However, Genentech subsequently revealed encouraging overall survival findings for its anti-TIGIT immunotherapy tiragolumab in individuals diagnosed with advanced or metastatic NSCLC.
BMS is actively pursuing an expansion of its portfolio of registrational assets over the next 18 months, with plans to increase the number from six to 12. This expansion encompasses a diverse array of therapies and treatments, including cell therapies targeting immunologic diseases, potential therapeutic interventions for multiple myeloma, and treatments for large B-cell lymphoma and metastatic castration-resistant prostate cancer, among others.