Failure rates in the biopharma industry remain high, with approximately 90% of investigational medicines failing to reach approval. Neurological drug candidates are particularly affected, with around 85% not making it through Phase II or III development.
In 2025, several significant clinical trial failures had major impacts on companies and their drug pipelines.
iTeos Therapeutics experienced a critical setback in May when its cancer immunotherapy candidate belrestotug, developed in partnership with GSK, failed to demonstrate clinically meaningful improvements in progression-free survival for non-small cell lung cancer. Disappointing results were also reported in a parallel study for head and neck cancer. Following these outcomes, GSK ended the collaboration and iTeos began searching for strategic alternatives. Two weeks later, iTeos decided to wind down operations until Concentra Biosciences acquired the company at $10.047 per share.
Alector faced a similar challenge after a late-stage failure of its frontotemporal dementia drug latozinemab, also partnered with GSK. Despite increasing progranulin levels as intended, latozinemab did not significantly slow disease progression or improve key biomarkers compared to placebo. The companies discontinued development of the drug, leading Alector to lay off nearly half its workforce to focus on other projects. However, Alector continues working with GSK on nivisnebart, another neuro asset currently in Phase II trials for early Alzheimer’s disease.
Novo Nordisk saw two major setbacks last month when semaglutide failed to show clinically meaningful effects against Alzheimer’s disease in the Phase III EVOKE and EVOKE+ studies involving over 3,800 patients. Although some improvement was observed in disease biomarkers, there was no significant impact on cognitive decline. These failures came amid broader difficulties for Novo Nordisk during 2025—including layoffs, declining market share for Wegovy, changes in leadership and board structure, and falling investor confidence that resulted in shares losing more than half their value year-to-date.
The failure of semaglutide has raised questions about the potential of GLP-1 drugs for treating neurodegenerative diseases. While recent studies suggested possible neuroprotective benefits of GLP-1 therapies—such as a retrospective analysis indicating a lower risk of dementia among users—the disappointing results from the EVOKE program may influence future research directions.
Bristol Myers Squibb (BMS) encountered problems with its recently approved schizophrenia treatment Cobenfy when it failed to reduce symptom severity as an adjunct therapy in the Phase III ARISE trial. This outcome led analysts at Leerink Partners to revise their long-term earnings forecasts downward by more than half—from $5.8 billion to $2.6 billion by 2030—and cast doubt on Cobenfy’s overall profile. Further data from ongoing studies testing Cobenfy for psychosis related to Alzheimer’s disease have been delayed due to irregularities detected at some study sites; results are now expected by late 2026.
Pfizer suffered another disappointment with its sickle cell disease antibody inclacumab after it failed the Phase III THRIVE-131 trial involving more than 240 patients who experienced multiple vaso-occlusive crises over the previous year. Pfizer took a $260 million impairment charge following this failure and has not disclosed future plans for inclacumab. The candidate originated from Pfizer’s $5.4 billion acquisition of Global Blood Therapeutics (GBT) in August 2022—a deal that has faced criticism due to subsequent clinical setbacks and product withdrawals.
These high-profile failures underscore both the risks inherent in biopharma R&D and their potential consequences for company strategy and financial performance.
“No conversations have occurred from the health authority perspective,” said Bristol Myers Squibb Chief Medical Officer Samit Hirawat regarding next steps following Cobenfy's ARISE trial results.
According to an Oct. 22 press release from Alector: “ensure continued progress across its portfolio.”
Analysts at BMO Capital Markets described Novo Nordisk’s EVOKE program as a “higher risk, high reward opportunity” given current uncertainties about Alzheimer’s etiology and GLP-1s’ therapeutic role.
Starboard Value criticized Pfizer's acquisition strategy as “failed” and stated that it “shocked the industry and raised serious questions about [Pfizer’s] BD capabilities.”
