2024 has been a year of significant developments in clinical trials, with readouts impacting treatment strategies across various disease areas. From novel HIV pre-exposure prophylaxis (PrEP) to advancements in spinal muscular atrophy (SMA) and obesity therapies, and progress in Alzheimer's disease, the pharmaceutical landscape continues to evolve.
HIV Prevention: Lenacapavir's Promising Results
Gilead's lenacapavir has shown groundbreaking results in HIV prevention. The PURPOSE 1 trial (NCT04994509), a Phase III study in cisgender women, demonstrated 100% efficacy with a twice-yearly injectable PrEP, eliminating HIV infections in the treatment arm compared to daily PrEP. At the AIDS24 conference in Munich, Germany, the data elicited a standing ovation. The PURPOSE 2 trial (NCT04925752) further validated lenacapavir's potential, showing 89% higher effectiveness than Truvada in cisgender men, transgender individuals, and gender non-binary patients, reducing HIV infections by 96% compared to background HIV incidence (bHIV).
Fiona Chisholm, senior infectious diseases analyst for GlobalData, noted, "Low or inconsistent adherence to daily oral pre-exposure prophylaxis (PrEP) represents a major challenge in HIV prevention... lenacapavir is on track to become the first twice-yearly injectable PrEP agent in the global HIV market." Gilead plans to offer generic licenses for lenacapavir PrEP to enhance accessibility in sub-Saharan African countries.
Spinal Muscular Atrophy: Apitegromab's Breakthrough
Scholar Rock's apitegromab achieved success in its Phase III SAPPHIRE trial (NCT05156320) for spinal muscular atrophy (SMA), leading to a 362% surge in the company's stock price. The trial met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in motor function, as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE). Apitegromab, a monoclonal antibody inhibiting myostatin activation, is the first muscle-targeted treatment candidate to show clinical proof-of-concept in SMA. Scholar Rock intends to submit a Biologics License Application (BLA) to the FDA and a marketing authorisation application (MAA) to the European Union in Q1 2025.
Obesity Therapies: GLP-1RAs Lead the Way
Significant progress has been made in glucagon-like peptide-1 receptor agonists (GLP-1RAs) for obesity. Eli Lilly's Zepbound outperformed Novo Nordisk's Wegovy/Ozempic (semaglutide) in the open-label Phase IIIb SURMOUNT-5 trial (NCT05822830). The trial enrolled 751 obese or overweight participants with comorbidities, such as hypertension and cardiovascular disease. By week 72, Zepbound recipients experienced an average weight loss of 20.2%, compared to 13.7% for Wegovy, representing a 47% greater relative weight loss.
Costanza Alciati, pharmaceutical analyst for GlobalData, stated, "Following these results and the negotiations that Eli Lilly is working on with different National Health authorities in multiple countries, we can expect Zepbound to take the lead in the obesity space soon... if Lilly's drug not only is more effective for weight loss but also offers better pricing options, it will certainly steal a big patient share."
Novo Nordisk's semaglutide also demonstrated benefits in the Phase III SELECT study (NCT03574597), reducing hospital admissions and overall length of hospital stay for adults with obesity or overweight and established cardiovascular disease (CVD) without diabetes. Additionally, Lilly’s Phase III SUMMIT trial (NCT04847557) indicated that tirzepatide reduced the risk of heart failure outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.
Alzheimer's Disease: Mixed Outcomes
While Cassava Sciences faced setbacks with its Alzheimer's drug simufilam after a Phase III failure in the ReThink-ALZ study (NCT04994483), Eisai reported positive data for Leqembi (lecanemab). In the Phase III CLARITY AD study (NCT03887455), Leqembi reduced cognitive decline on the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) by 0.95 points compared to the expected decline, as observed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study (3.09 vs 4.04). The data was presented at the 2024 Alzheimer’s Association International Conference (AAIC).
