Trials to watch in 2025
Clinical trials frequently result in breakthroughs for diseases with limited treatment options, potentially transforming the future of medicine and enhancing patient outcomes and quality of life. Positive trial results can accelerate regulatory approvals, facilitating the introduction of new treatments to the market. These outcomes also influence stock prices, and investor sentiment, and can shape the dynamics of the pharmaceutical industry. Furthermore, clinical trials play a crucial role in shaping healthcare policies and guidelines. The findings can prompt changes in treatment protocols, guiding healthcare providers in determining the most effective care for patients. Many trials target conditions that currently lack viable treatments, and their success could address significant gaps in healthcare, particularly for rare or chronic diseases. Monitoring clinical trials also helps researchers, regulators, and the public identify potential side effects and safety concerns, ensuring that new therapies are both safe and effective. Finally, the results of high-profile trials can affect funding and resource distribution within the healthcare sector, influencing public and private investment in research and development.
1. HVTN 142
The VIR-1388 vaccine, designed for HIV prevention, is currently in a Phase 1 trial to evaluate its safety, reactogenicity, and immunogenicity in healthy adults aged 18–55 who are HIV-negative. It employs a cytomegalovirus (CMV) vector to stimulate strong and lasting T-cell responses, aiming to enhance the immune response compared to its predecessor, VIR-1111, which was safe but produced a weaker response. The study, backed by prominent institutions such as the US National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation, is being conducted in the USA and South Africa. Its success could have a significant impact on public health efforts to combat HIV.
2. RECOVER studies
The National Institutes of Health (NIH) is set to initiate clinical trials aimed at exploring potential treatments for long-term symptoms resulting from COVID-19, such as sleep issues, exercise intolerance, and the worsening of symptoms after physical or mental exertion, known as post-exertional malaise (PEM). These mid-stage trials are part of NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative and will complement six other RECOVER studies currently recruiting participants across the U.S. to test treatments for viral persistence, neurological symptoms (including cognitive dysfunction like brain fog), and autonomic nervous system dysfunction. The new trials aim to enroll around 1,660 participants at 50 study sites to address some of the most common and debilitating symptoms experienced by those with long COVID. For individuals struggling with unreliable sleep, limited physical exertion, and increased illness after once-simple tasks, the resulting physical and mental distress can lead to profound feelings of helplessness. There is an urgent need to find solutions to help those affected by long COVID regain a sense of normalcy.
RECOVER-SLEEP: Platform Protocol
RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)
3. Amyotrophic lateral sclerosis clinical trials
Patients with amyotrophic lateral sclerosis (ALS) have faced significant challenges in recent weeks after Amylyx Pharmaceuticals withdrew its leading drug, Relyvrio, from the market on April 4, 2024, due to a Phase III trial failing to meet its primary endpoint. Initially hailed as a potential breakthrough for patients by slowing disease progression, the Phase III results revealed no difference between the drug and a placebo. Despite this disappointment, the Muscular Dystrophy Association remains optimistic about the numerous promising candidates in development. Currently, there are only six FDA-approved drugs for ALS, with just one—riluzole—serving as a disease-modifying therapy, highlighting the urgent need for additional treatment options. Four ALS drugs to watch are ABBVCLS-7262, AP-101, CNMAU-8, and RAPA-501. These candidates are expected to transform the treatment landscape for patients with ALS.
HEALEY ALS Platform
This platform trial aims to speed up drug development and improve treatment options for amyotrophic lateral sclerosis by testing multiple drugs simultaneously and adaptively. This approach has proven successful in cancer trials. Compared to traditional drug development, platform trials are expected to identify effective therapies more quickly (averaging 3.4 years instead of 8.5) and with fewer participants (approximately 880 versus 1,400), as well as fewer on placebo (around 220 instead of 700). This trial is enhancing the search for treatments by allowing researchers to evaluate several drugs at once.
AP101-02
AL-S Pharma is conducting a Phase IIa trial (NCT05039099) to evaluate its candidate AP-101 in patients with familial amyotrophic lateral sclerosis (fALS) and sporadic amyotrophic lateral sclerosis (sALS). The study aims to complete by June 2024 and involves approximately 63 participants. AP-101 is an intravenous monoclonal antibody designed to activate superoxide dismutase-1 (SOD1), a protein whose mutations are associated with ALS.
CNMAu8.205 OLE
Clene’s CNMAu-8 is currently undergoing a Phase II trial (NCT05299658). This open-label extension study is evaluating CNMAu-8 in 40 patients with early symptomatic ALS who are on stable background therapy. The oral treatment is administered daily over 48 weeks, with a completion date of December 2024. Developed using catalytically active gold nanocrystals, CNMAu-8 aims to inhibit damaging processes that affect myelination and protect neurons. Its ability to cross the blood-brain barrier allows it to reach and safeguard central nervous system neurons effectively. Preliminary results indicate that it is safe, well-tolerated, and shows survival benefits that surpass many other candidates. If successful, CNMAu-8 could be a game-changer for ALS patients.
RAPA-501-ALS
Rapa Therapeutics is conducting a Phase II/III trial (NCT04220190) of its candidate RAPA-501, an open-label, non-randomized, multi-center study assessing T-cell therapy for ALS patients. RAPA-501 is an autologous T-cell therapy designed to protect motor neurons from inflammation. The T cells are produced ex vivo using epigenetic reprogramming to create a population enriched for dual anti-inflammatory characteristics from hybrid TREG and Th2 cells. Participants will receive up to four infusions, spaced six weeks apart, over the 30-week study period, which plans to enroll 41 patients and is set to be completed by July 2025.
