Safety Concerns Take Center Stage as Obesity Drug Race Heats Up

In the fiercely competitive obesity drug market, pharmaceutical giants and emerging players alike are vying for dominance, with safety profiles becoming a crucial differentiator. Recent data presented at the American Diabetes Association's 85th Scientific Sessions in Chicago has put the spotlight on tolerability issues across multiple candidates, potentially reshaping the landscape of weight loss treatments.

Frontrunners Face Scrutiny

Eli Lilly and Novo Nordisk, current leaders in the obesity drug space, both encountered challenges at the ADA meeting. Lilly's investigational antibody bimagrumab, when combined with Novo's Wegovy (semaglutide), showed promise in preserving muscle mass while promoting weight loss. However, BMO Capital Markets analysts expressed concerns over "transient increases in ALT and more permanent elevations in lipases," indicating potential liver and pancreatic issues.

Lilly's oral candidate orforglipron also faced criticism for persistent gastrointestinal side effects in its Phase III ACHIEVE-1 trial for type 2 diabetes. William Blair analysts noted that high-dose patients experienced nausea, vomiting, and constipation that did not subside as typically seen with other GLP-1 therapies.

Novo Nordisk, meanwhile, presented data on its CagriSema combination therapy, emphasizing a side effect profile "comparable with the GLP1-RA class." However, William Blair analysts highlighted a potential drawback: 12% of patients in the REDEFINE-1 study experienced injection-site reactions, primarily attributed to the cagrilintide component.

Challengers Enter the Fray

Amgen's MariTide, aiming to break into the obesity market, faces an uphill battle after disappointing Phase II results. The drug achieved 19.9% weight loss in patients who completed the 52-week trial, falling short of the 25% expectation. Tolerability remains a concern, with 92% of patients in the highest dose group reporting nausea and vomiting.

In contrast, Viking Therapeutics' VK2735 has shown promise, with Truist Securities analysts giving it "a real shot at making material inroads in obesity." The drug demonstrated 13.1% placebo-adjusted weight loss at 13 weeks in Phase II trials, with a competitive tolerability profile based on study discontinuation rates.

Market Implications

The stakes are high in the obesity drug market, with GLP-1 therapies expected to comprise nearly 10% of a projected $1.75 trillion prescription drug market by 2030, according to Evaluate. As companies race to develop the most effective and tolerable treatments, the focus on safety profiles could significantly influence market share and patient adoption in the coming years.