BMS-986299

Novartis is also stopping development of a BTK inhibitor in Sjögren’s syndrome. Novartis’ anti-TIM-3 antibody has flunked a phase 3 blood cancer trial, prompting the Swiss drugmaker to pull the drug candidate from its pipeline. The failed study was the biggest test to date of an immuno-oncology target into which a who’s who of leading drug developers have pumped money. In Novartis’ phase 3 trial, patients with intermediate or worse risk myelodysplastic syndrome or chronic myelomonocytic leukemia-2 received the chemotherapy drug azacitidine plus either the TIM-3 candidate MBG453 or placebo. MBG453, also known as sabatolimab, was designed to address the unmet needs of patients who are unfit for hematopoietic stem cell transplantation. TIM-3 is expressed by immune effector cells, where it acts as an immune checkpoint, and leukemic stem cells, leading Novartis to identify the receptor as a way to simultaneously activate the immune system and suppress the proliferation of cancer cells. That theory failed to translate into efficacy in phase 3. Novartis broke the news that the late-stage study missed its primary endpoint, overall survival, as part of its fourth-quarter results (PDF) on Wednesday. The Swiss drugmaker responded to the setback by stopping development of sabatolimab, which was in phase 1 and 2 trials in acute myeloid leukemia and low-risk myelodysplastic syndrome at the time of the pivotal flop. Novartis’ retreat from TIM-3 makes GSK’s cobolimab the most advanced candidate against the receptor. While Novartis focused on blood cancers, GSK and other big names with TIM-3 candidates have largely looked at solid tumors. GSK, which acquired its TIM-3 candidate in the $5.1 billion Tesaro takeover, is running a phase 2/3 clinical trial in non-small cell lung cancer patients.  The list of other active TIM-3 programs has thinned in recent years. Roche removed (PDF) a PD-1xTIM-3 bispecific from its pipeline in 2022. AstraZeneca is continuing to study its rival bispecific in phase 1 and 2 trials, and Incyte is enrolling a phase 2 endometrial cancer trial to assess its monoclonal antibody. Bristol Myers Squibb terminated a phase 1 trial of one TIM-3 candidate, BMS-986299, in 2022 because its “business objectives” had changed. A phase 1/2 clinical trial of a second TIM-3 asset, the Five Prime Therapeutics-partnered BMS-986258, is still active but BMS stopped enrollment at around one-third of its original target around the time the other study was terminated. Eli Lilly has also axed a TIM-3 drug. Sabatolimab was the big pipeline news in Novartis’ results but the Swiss drugmaker also shared smaller updates. Novartis is stopping development of the BTK inhibitor remibrutinib in Sjögren’s syndrome but is continuing to advance toward phase 3 data in three other indications. And a HIF2A inhibitor disappeared from Novartis’ pipeline, one month after the company stopped enrollment in a phase 1/1b trial early.