Clinical trials are entrenched with variables, which can teeter them towards success or failure. Success rates often vary by disease area, development strategy and drug type, and one analysis found that overall drug development success rates have hovered around 5% in recent years. Phase II consistently stood out as one of the hardest steps to clear.
Another analysis found that industry-sponsored Phase II and Phase III trial terminations roughly doubled from 2013 to 2023, with more late-stage studies ending because of business decisions, portfolio shifts or commercial strategy.
A missed endpoint, however, does not always mean a program is shelved or scrapped. Toronto-based Biossil, for example, recently raised about $70 million and is using AI to identify drug candidates that did not make it through their original clinical trials.
When trials fail, they can take different forms. Some studies lead companies to discontinue programs, while others produce mixed data that keep development moving in a narrower or revised direction.
Below are some notable late-stage clinical trial failures and mixed readouts reported in 2026.
Major Endpoint Misses and Discontinued Programs
Merck and Eisai’s LITESPARK-012 in Renal Cell Carcinoma
Merck and Eisai reported that the Phase III LITESPARK-012 trial missed both of its main goals in first-line advanced clear cell renal cell carcinoma, a type of kidney cancer.
The study tested two combination regimens against Keytruda plus Lenvima, an approved first-line option in this setting. The trial did not show a significant improvement in progression-free survival, or how long patients lived without their cancer worsening, or overall survival. The companies are continuing to evaluate the data.
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Immunovant’s Batoclimab in Thyroid Eye Disease
Immunovant reported that two Phase III studies of batoclimab in thyroid eye disease failed to meet their primary endpoint.
The studies enrolled adults with active, moderate-to-severe thyroid eye disease, an autoimmune condition that can cause inflammation, eye bulging and vision-related symptoms. The trials measured whether patients had at least a 2 mm improvement in proptosis, or eye bulging, at Week 24.
Immunovant is now focusing on IMVT-1402, another investigational therapy in its pipeline.
Theravance’s Ampreloxetine in Neurogenic Orthostatic Hypotension
Theravance Biopharma’s Phase III CYPRESS study tested ampreloxetine in people with multiple system atrophy who also had symptomatic neurogenic orthostatic hypotension.
Multiple system atrophy is a rare neurological disease, and neurogenic orthostatic hypotension is a related blood pressure problem that can cause dizziness or fainting after standing.
The trial missed its primary endpoint. After the readout, Theravance said it would stop developing ampreloxetine, cut operating expenses by about 60% and restructure the company, affecting about 50% of its workforce.
Quince’s eDSP in Ataxia-Telangiectasia
Quince Therapeutics’ pivotal Phase III NEAT trial of eDSP missed its primary endpoint in ataxia-telangiectasia, a rare inherited disorder that affects the nervous and immune systems.
The study measured neurological effects using an ataxia rating scale at month six. It did not show a statistically significant improvement compared with placebo. The trial also missed a key secondary endpoint based on clinical global impression of disease severity.
Quince said it would stop clinical development of eDSP, preserve cash and review available options.
Gossamer Bio’s Seralutinib in Pulmonary Arterial Hypertension
Gossamer Bio’s Phase III PROSERA study tested seralutinib in pulmonary arterial hypertension, a serious condition that raises blood pressure in the lungs and strains the heart.
The trial measured how far patients could walk in six minutes, a common way to assess exercise capacity in pulmonary hypertension studies. Patients receiving seralutinib improved by a median of 28.2 meters from baseline, compared with 13.5 meters for placebo at Week 24.
However, the difference was not strong enough to meet the trial’s required statistical threshold. Gossamer plans to meet with the FDA to discuss a potential path forward.
Mixed Readouts Where Development Continued
Biogen/Ionis’ Diranersen in Alzheimer’s Disease
Biogen’s Phase II CELIA study of diranersen missed its primary endpoint in early Alzheimer’s disease.
Diranersen, an investigational antisense oligonucleotide, is designed to reduce the production of tau, a protein linked to Alzheimer’s disease progression. The study used a dementia rating tool that measures cognition and daily function.
Although the study missed its primary endpoint, Biogen said diranersen reduced tau-related biomarkers and showed signs of slowing clinical decline across studied doses. The company plans to continue testing the drug in later-stage studies that could support future approval.
Roche’s Giredestrant Combination in Advanced Breast Cancer
Roche’s Phase III persevERA Breast Cancer study missed its primary objective in ER-positive, HER2-negative locally advanced or metastatic breast cancer.
The trial tested giredestrant plus palbociclib against letrozole plus palbociclib as a first-line treatment. The result trended in Roche’s favor but was not strong enough to meet the study’s main goal of improving progression-free survival.
Roche is continuing to evaluate giredestrant in other breast cancer trials.
GRAIL’s NHS-Galleri Cancer Screening Trial
GRAIL’s NHS-Galleri trial tested whether adding the Galleri blood test to usual cancer screening could help detect cancer earlier in people without symptoms.
The study included more than 142,000 people aged 50 to 77 in England. It did not significantly reduce the combined number of Stage III and Stage IV cancer diagnoses.
GRAIL reported more favorable trends in a pre-specified group of 12 deadly cancers, including fewer Stage IV diagnoses and higher cancer detection when Galleri was added to standard screening. Additional NHS-Galleri and PATHFINDER 2 data were slated for ASCO 2026.
FAQs
Why is Phase II considered difficult in drug development?
Phase II is often where researchers begin to see whether a treatment shows enough efficacy and safety in patients to justify a larger and more expensive Phase III study.
Does missing a primary endpoint always mean a drug failed?
Not necessarily. Some studies miss their main goal but still show positive biomarker data, subgroup findings or secondary outcomes that support continued development.
Why do some companies continue development after a failed trial?
Companies may continue development if they believe the data still support a narrower patient group, a different dose, another indication or a revised study design.
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