2025’s Top 10 Clinical Trial Flops in Global Pharma

Clinical trials are always high-stakes gambles. 2025 has been a sobering year for the industry’s biggest players, from Novo Nordisk to Pfizer and Sanofi. Analyzing these setbacks allows the industry to learn vital lessons and refine strategies for developing new drugs and therapeutic methods.

The past year has demonstrated that even multi-billion dollar M&A deals and innovative mechanisms of action do not guarantee success in late-stage development. Most failures occurred during Phase II and Phase III trials, leading to significant asset impairments, plummeting stock prices, and complete pipeline overhauls.

Analysis of Key Failures

1. Milvexian (Factor XIa inhibitor) — Johnson & Johnson / BMS
The Phase III trial of this promising anticoagulant was halted early due to a lack of therapeutic efficacy. J&J and BMS terminated the study, which intended to enroll 16,000 patients and was scheduled for completion in late 2026. Had the trial succeeded, Milvexian could have become the first Factor XIa inhibitor approved for acute coronary syndrome. For the partners, this failure dents hopes of it becoming a “mega-blockbuster” to replace Eliquis (with sales exceeding $10 billion annually) before its patent expiration in 2028.

2. Inclacumab (P-selectin inhibitor) — Pfizer
Pfizer reported that while Inclacumab was generally well-tolerated, it showed a wide range of side effects. Crucially, the drug failed to demonstrate benefits in reducing the rate of vaso-occlusive crises in patients with sickle cell disease. This failure jeopardizes the return on the $5.4 billion acquisition of Global Blood Therapeutics. Pfizer has already recorded a $260 million impairment charge related to this clinical setback.

3. Troriluzole (Glutamate modulator) — Biohaven
Troriluzole is a prodrug of riluzole, which was approved in 1995 as the first treatment for ALS. However, in recent Phase III trials for obsessive-compulsive disorder (OCD), the molecule failed to show a significant therapeutic signal. The failure led to the closure of a program that had seen five years of heavy investment. Biohaven must now focus on other assets to meet market expectations following the $11.6 billion sale of its migraine portfolio to Pfizer.

4. Anselamimab (Anti-fibril antibody) — AstraZeneca
AstraZeneca acquired Anselamimab through its $1.2 billion purchase of Caelum Biosciences in 2021, when the therapy was already in Phase III. However, in trials for AL amyloidosis, the drug failed to statistically improve mortality rates. Prior to this, analysts projected peak annual sales between $1 billion and $3 billion. The Alexion unit is now attempting to find a regulatory path through subgroup analysis.

5. Simufilam (Target: Filamin A protein) — Cassava Sciences
A second consecutive Phase III failure confirmed the lack of impact on Alzheimer’s disease progression. CEO Rick Barry called the results “unambiguous,” stating the company is ending Simufilam’s development for this indication due to zero evidence of patient benefit. Cassava’s stock plummeted by over 20%. With cash reserves only lasting until 2027, the loss of its primary valuation driver puts the company’s future at risk.

6. Astegolimab (Anti-ST2 monoclonal antibody) — Roche
The promising anti-ST2 monoclonal antibody failed to reduce exacerbation rates in a large Phase III COPD study. Despite Phase II success, the pivotal trial was deemed a failure. This freezes Roche’s plans for a 2025 regulatory filing and questions the ROI on the license originally acquired from Amgen. Roche attributed the result to an unexpectedly low rate of exacerbations in the placebo group.

7. Repibresib (BET inhibitor) — Vyne Therapeutics
The BET inhibitor gel failed to outperform placebo in restoring skin pigmentation for vitiligo patients. The Phase IIb study missed both primary and secondary endpoints. Following the announcement, Vyne’s stock crashed by 74%, leading to the program’s cancellation. The company was subsequently forced into a merger with Yarrow Bioscience.

8. Itepekimab (IL-33 inhibitor) — Sanofi / Regeneron
Conflicting Phase III results in COPD forced the partners to abandon 2025 filing plans. While one study showed significant reduction in exacerbations, the second essentially failed. This is a critical delay for Sanofi, which needs to replace revenue from its blockbuster Dupixent (generating over €10 billion annually) before the 2031 patent cliff.

9. Monlunabant (CB1 receptor inverse agonist) — Novo Nordisk
A mid-stage study for diabetic nephropathy showed no improvement in kidney function while confirming risks of neuropsychiatric side effects (anxiety, irritability, and sleep disturbances). This puts the $1.1 billion acquisition of Inversago Pharma at risk. These psychiatric side effects significantly limit the drug’s potential even in the lucrative obesity market.

10. Setrusumab (Sclerostin inhibitor) — Ultragenyx
Two late-stage studies in osteogenesis imperfecta failed to show a significant reduction in fracture rates. Upon the news, the biotech’s stock dropped 43%, and its partner Mereo BioPharma fell by over 70%. The failure casts doubt on the viability of a program once considered a key driver for the company’s growth.

Financial Risks and Losses Summary

2025 has clearly demonstrated that even with immense financial resources, fundamental science remains unpredictable. For major corporations, these failures highlight the necessity of more rigorous target selection at earlier stages.

Source: FierceBiotech.