February 22, 2024

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Top 10 Global Clinical Trial Failures in 2023

Top 10 Global Clinical Trial Failures in 2023

Top 10 Global Clinical Trial Failures in 2023

According to Deloitte’s statistics, the development cost of a single new drug is approximately $2.3 billion, signifying that pharmaceutical companies must take significant risks to bring these new drugs to market.

When these drug development projects face setbacks, it is crucial to reflect on the issues that arise and strive to propose better scientific foundations and solutions.


Fierce Biotech has conducted an annual review of the highly anticipated top 10 clinical trial failures in 2023, involving both multinational corporations (MNCs) and biotech companies.

The announcements of these clinical failures have led to stock market declines for some drugs, sparking concerns within the industry about the entire category of drugs.


However, lessons learned from past failures and experiences gained from successes are equally important.

It is hoped that these clinical trial failures serve as a warning to the industry, and that the biopharmaceutical sector in 2024 can produce better data and treatment methods to meet more unmet clinical needs.




1. HIV Vaccine

Indication: HIV
Companies: Johnson & Johnson (J&J) / Janssen
Modality: Vaccine

The failure of Janssen’s HIV vaccine indicates a setback for Johnson & Johnson in the field of infectious diseases. On January 18, 2023, Janssen announced the failure of the Mosacio Phase III clinical trial conducted globally. The trial studied the HIV vaccine regimen in 3,900 enrolled patients, involving the administration of an adenovirus vector-based vaccine four times within a year, along with the use of a soluble protein drug during the third and fourth follow-up visits. Janssen found that this therapy did not prevent HIV, and the study was expected not to reach its primary endpoint, leading to the termination of the clinical trial.

This marks the second failure for Johnson & Johnson in developing an HIV preventive vaccine. In 2021, J&J halted the development of a similar vaccine called Imbokodo (or HVTN705) after a Phase IIb trial in five Southern African countries, where the vaccine’s protective efficacy was calculated at 25.2%. Despite the overall good tolerability, the low efficacy couldn’t support further research, leading to the discontinuation of the vaccine’s development.

In the weeks following the failure of the Mosacio Phase III trial, Fierce Pharma reported that J&J initiated a comprehensive overhaul of its infectious disease research and development department, including layoffs and a complete cessation of HIV vaccine development. By August 2023, the infectious disease department at J&J had ceased its R&D efforts, and the development of marketed products related to HIV shifted to other departments within the company.


2. Rezpeg

Indication: Autoimmune Diseases
Company: Nektar Therapeutics
Modality: IL-2

In February 2023, Eli Lilly announced the failure of the Phase II clinical trial for rezpegaldesleukin, a new IL-2 drug developed in collaboration with Nektar Therapeutics, for the treatment of lupus erythematosus. Nektar had been conducting clinical studies focused on lupus erythematosus, hoping to expand the development potential of its drug. However, Eli Lilly ultimately abandoned the clinical trial for treating lupus erythematosus, stating that it would reassess the prospects of rezpeg in the treatment of atopic dermatitis. Subsequently, in April 2023, Eli Lilly returned rezpeg to Nektar, along with the original data from its clinical studies.

Months later, in August 2023, Nektar pointed out that its former partner Eli Lilly had made significant errors in the statistical analysis of clinical data for rezpeg. The erroneous data came from two clinical studies conducted by Eli Lilly on rezpeg for atopic dermatitis and psoriasis. Eli Lilly confirmed these errors, leading Nektar to file a lawsuit against Eli Lilly.

In October 2023, Nektar released the final results of its Phase Ib trial, showing that rezpeg achieved relief and improvement in atopic dermatitis during 12 weeks of treatment, ensuring sustained efficacy within 36 weeks. Nektar initiated a Phase IIb study later that month.


3. BEN-2293

Indication: Atopic Dermatitis
Company: BenevolentAI
Modality: Pan-Trk Inhibitor

AI pharmaceuticals, despite their surge in popularity, encountered a setback with the failure of AI pharmaceutical company BenevolentAI’s core product, the Pan-Trk inhibitor BEN-2293, in treating atopic dermatitis. In April 2023, BenevolentAI announced the failure of the Phase IIa study for BEN-2293, which, while achieving the safety primary endpoint, missed the secondary efficacy endpoints related to reducing itching and inflammation.

Trk is widely known as a target for cancer drugs, but BenevolentAI’s artificial intelligence platform identified these targets as mediators inducing itching and inflammation in atopic dermatitis. BenevolentAI believed that BEN-2293 had the potential to treat symptoms of mild to moderate atopic dermatitis with fewer side effects compared to existing drugs.

However, the drug did not outperform the placebo in improving the area and severity of eczema or itching, which were secondary endpoints in the clinical study. Subsequently, BenevolentAI abandoned the development of BEN-2293.


4. Sitravatinib

Indication: Non-Small Cell Lung Cancer
Company: Mirati Therapeutics
Modality: Kinase Inhibitor

Mirati Therapeutics was poised to usher in a new era of cancer treatment through Sitravatinib, but the anticipated positive results did not materialize. In May 2023, Mirati expected to unveil the results of the Phase III SAPPHIRE trial, demonstrating a 3.5-month overall survival benefit from Sitravatinib. Unfortunately, the final analysis showed that the drug did not reach this primary endpoint.

Sitravatinib is a spectrum-selective kinase inhibitor, and Mirati hoped it would help overcome resistance to immune checkpoint inhibitors. In the randomized Phase III SAPPHIRE study, Mirati evaluated Sitravatinib in combination with nivolumab during or after platinum chemotherapy for non-squamous NSCLC patients with disease progression. The study aimed to compare the efficacy of the study drug in combination with nivolumab versus docetaxel in this patient population. Patients in the treatment group received daily oral Sitravatinib in addition to intravenous infusions of nivolumab lasting at least 30 minutes. The primary endpoint evaluated was overall survival, with secondary endpoints including adverse events, objective response rate, and progression-free survival.

Due to the failure to reach the primary endpoint, Mirati chose to terminate the development of the drug. However, BeiGene holds the development and commercialization rights for the drug in Asia, New Zealand, and Australia.


5. Tarcocimab Tedromer

Indication: Diabetic Macular Edema
Company: Kodiak Sciences
Modality: Antibody-Conjugated Biopolymer

In July 2023, Kodiak Sciences announced that its antibody-conjugated biopolymer (ABC) targeting VEGF, Tarcocimab Tedromer (KSI-301), did not meet the primary endpoints in two Phase III clinical trials for the treatment of retinal vascular diseases. Furthermore, the results indicated an increased incidence of cataracts in patients treated with Tarcoc

imab Tedromer.

The two clinical trials, named BEACON and DAZZLE, evaluated the efficacy and safety of Tarcocimab Tedromer in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). In both trials, the drug did not demonstrate non-inferiority to aflibercept (Eylea), the current standard of care, for the primary endpoints.

Kodiak Sciences initially focused on nAMD, but the disappointing results led to a broader reassessment of the drug’s development strategy. The company decided to shift its focus to anti-PDGF (platelet-derived growth factor) therapies for retinal vascular diseases.


6. Melterocercant

Indication: Alzheimer’s Disease
Company: AC Immune
Modality: Tau Vaccine

The failure of the Phase II clinical trial for Melterocercant, AC Immune’s tau vaccine for Alzheimer’s disease, marked a significant setback for the development of disease-modifying therapies for Alzheimer’s. In August 2023, AC Immune announced that the tau vaccine did not meet the primary endpoint in a Phase II study involving patients with mild to moderate Alzheimer’s disease.

The randomized, double-blind, placebo-controlled Phase II study, named ACI-35-302, aimed to assess the safety, tolerability, and efficacy of Melterocercant. The trial enrolled 430 patients across multiple countries and evaluated the vaccine’s ability to slow cognitive decline and functional impairment in Alzheimer’s patients.

The disappointing results prompted AC Immune to terminate the clinical development of Melterocercant for Alzheimer’s disease. The company shifted its focus to other programs in its pipeline, including treatments for neurodegenerative diseases and neuroinflammation.


7. Cerliponase Alfa

Indication: CLN2 Disease (Late Infantile Neuronal Ceroid Lipofuscinosis Type Special
Companies: BioMarin Pharmaceutical, National Institute for Health and Welfare, Sarepta Therapeutics
Modality: Enzyme Replacement Therapy

Cerliponase alfa, developed as an enzyme replacement therapy (ERT) for CLN2 disease, faced a setback when BioMarin Pharmaceutical, the lead developer, announced the failure of a Phase III trial. CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis type 2, is a rare genetic disorder affecting the nervous system in children.

In the Phase III trial, named CLN2-303, Cerliponase Alfa did not demonstrate a statistically significant improvement in the primary endpoint, which measured the change from baseline in the Motor Function Measure 32 (MFM-32) score compared to the control group at 48 weeks. The trial enrolled pediatric patients aged 3 to 16 years with CLN2 disease.

BioMarin expressed disappointment with the results and announced plans to discuss the findings with regulatory authorities to determine the future development strategy for Cerliponase Alfa in CLN2 disease.


8. BAT1806

Indication: Hemophilia A
Company: BioAtla
Modality: Factor VIII (FVIII P & E Site) Inhibitor

BioAtla faced a setback in the development of BAT1806, a factor VIII (FVIII) inhibitor for the treatment of hemophilia A. In September 2023, the company announced that the Phase II trial for BAT1806 did not meet the primary endpoint of reducing annualized bleeding rates compared to on-demand therapy with standard-of-care factor VIII.

The Phase II trial, named HEMERA, evaluated the safety and efficacy of BAT1806 in preventing bleeding episodes in previously treated patients with severe hemophilia A. BAT1806 is a site-specifically modified FVIII molecule designed to reduce bleeding events by providing prolonged protection against bleeding episodes.

The disappointing results led BioAtla to reassess the development plan for BAT1806. The company emphasized its commitment to advancing innovative therapies and exploring new opportunities in the field of hemophilia.


9. GM-CT-01

Indication: Myelofibrosis
Company: Gilead Sciences
Modality: Galectin-3 Inhibitor

Gilead Sciences faced a setback in its efforts to address myelofibrosis, a condition characterized by the scarring of the bone marrow. In November 2023, Gilead announced the discontinuation of the Phase II clinical trial for GM-CT-01, a galectin-3 inhibitor, in myelofibrosis.

The Phase II trial aimed to assess the safety and efficacy of GM-CT-01 in combination with ruxolitinib, a standard-of-care treatment for myelofibrosis. The decision to discontinue the trial was based on a futility analysis that suggested the combination therapy was unlikely to show a significant improvement in the primary endpoint of spleen response rate compared to ruxolitinib alone.

Despite the setback in myelofibrosis, Gilead remains committed to its broader research and development efforts in various therapeutic areas, including hematologic malignancies.


10. VTX-001

Indication: Acute Myeloid Leukemia
Company: Vor Biopharma
Modality: HSC-Targeted Therapies

Vor Biopharma faced a challenge in the development of VTX-001, a hematopoietic stem cell (HSC)-targeted therapy for acute myeloid leukemia (AML). In December 2023, the company announced the discontinuation of the Phase I clinical trial for VTX-001.

VTX-001 was designed as a potential treatment for AML by selectively targeting and eliminating cancer cells while preserving healthy HSCs. The Phase I trial aimed to evaluate the safety, tolerability, and preliminary efficacy of VTX-001 in patients with AML.

Vor Biopharma cited challenges in achieving optimal therapeutic levels of VTX-001 in the bone marrow as a key factor in the decision to discontinue the trial. Despite this setback, the company continues to explore novel approaches to advance its pipeline of HSC-targeted therapies for various hematologic malignancies.



The pharmaceutical and biotech industry is characterized by high risks and uncertainties in the development of new therapies. Clinical trial failures, while disappointing, provide valuable insights that contribute to the iterative process of drug development. Each setback offers an opportunity for the industry to learn, adapt, and strive for innovation in addressing unmet medical needs.

As the industry navigates the challenges of drug development, collaboration, transparency, and a commitment to scientific rigor are essential. Lessons learned from clinical failures contribute to the collective knowledge base, guiding researchers and developers toward more informed decisions and improved strategies for bringing innovative and effective treatments to patients in need.

It is crucial for stakeholders in the biopharmaceutical sector to continue embracing a culture of innovation and resilience, recognizing that setbacks are inherent in the pursuit of groundbreaking therapies. By fostering an environment that encourages collaboration and learning from both successes and failures, the industry can continue to advance the frontiers of medicine and enhance the quality of care for patients worldwide.

Top 10 Global Clinical Trial Failures in 2023

(source:interneta4Bh3Gx4BfEKJRFVvzOmzA, reference only)

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