The phase 3 comeback story Bristol Myers Squibb investors were eagerly anticipating is not to be—at least not this year.
The highly anticipated Adept-2 study will not read out by year-end as previously planned after BMS identified “irregularities due to clinical trial execution at a small number of study sites,” the company said Wednesday.
Adept-2 is one of three phase 3 trials in which BMS is testing its blockbuster hopeful Cobenfy in psychosis associated with Alzheimer’s disease.
With the delay, BMS looks to finish 2025 without a much-needed comeback story for Cobenfy after another trial flop this spring for the drug as an adjunctive treatment for schizophrenia. More broadly, out of the six pivotal trials BMS has read out this year, only one success was booked on one of the dual primary endpoints in a multiple myeloma trial of iberdomide.
Alzheimer’s psychosis is a large market, as BMS estimates about half of the 6 million U.S. patients with Alzheimer’s suffer from hallucinations and delusions.
Investors have high expectations for Adept-2 “given the size of the market opportunity, need for momentum in the Cobenfy clinical trial launch, and recent setbacks with other late-stage programs at Bristol Myers,” William Blair analysts pointed out in a Dec. 3 note.
Investors first got anxious about Adept-2 after executive comments made during BMS’ second-quarter earnings call in July. At that time, BMS’ then-chief medical officer Samit Hirawat, M.D., said the New Jersey pharma was conducting trial site reviews of Adept-2 as part of an effort to improve success for all BMS clinical programs.
Now, with the reviews having identified “irregularities,” BMS has decided to exclude patient data from those sites. Following agreement with the FDA, an independent party conducted an interim data analysis of both efficacy and safety while BMS remained blinded to study data. At the recommendation of the data monitoring committee, BMS will start enrolling new patients into Adept-2, which is now expected to read out by the end of 2026.
The company’s Adept-1 and Adept-4 trials are expected to read out by the end of next year as originally planned, the company said.
Because BMS has said that at least two positive trials are required for a filing for approval, the Adept-2 delay alone does not impact the company’s original regulatory plan.
While site irregularities and a delay might raise concerns, the William Blair team deemed the data monitoring committee’s recommendation to continue the trial as a positive sign, because, they wrote, “if there was no signal, why bother increasing enrollment?”
The affected sites are located in the U.S., according to William Blair analysts who spoke with BMS’ investor relations team. The company is not disclosing the number of patients affected nor the exact nature of the irregularities, other than explaining that the situation involved a multitude of issues, according to William Blair. The study previously closed enrollment after reaching 400 patients, according to ClinicalTrials.gov.
Those sites’ data will also be excluded from Adept-1 and -4 if they participated in those parallel Cobenfy studies, according to the analysts.
“Our decision to exclude patient data from sites where irregularities were observed reflects our unwavering commitment to safeguarding the integrity of our studies,” Laura Gault, M.D, Ph.D., who heads up neuroscience drug development at BMS, said in a Dec. 3 statement. “Psychosis related to Alzheimer’s Disease remains an area of tremendous unmet medical need, and maintaining rigorous standards is essential as we work to identify innovative treatment options for patients and families affected by this devastating condition.”
BMS needs several wins to instill confidence in its growth potential for 2030 and beyond. Besides Cobenfy’s flop as an adjunctive schizophrenia treatment, the company also recorded phase 3 failures this year for Opdualag, Camzyos, Reblozyl and, most recently, Johnson & Johnson-partnered factor XIa inhibitor milvexian.
Hirawat stepped down amid the string of trial setbacks and was recently succeeded by AstraZeneca veteran Cristian Massacesi, M.D.