The race to develop an oral medication for weight loss has a new contender. Hengrui Pharma and its partner, Kailera, have announced promising topline data from a phase 2 trial of their investigational drug, ribupatide, demonstrating weight loss of up to 12.1% in participants.
Ribupatide, a dual GIP and GLP-1 receptor agonist, is already being investigated as a once-weekly injectable for obesity, having previously shown significant weight loss – 23.6% – in phase 2 trials. While the oral formulation doesn’t match the efficacy of the injectable, the observed 12.1% reduction is comparable to results seen with recently approved and emerging oral weight loss medications.
Currently available and late-stage oral options, such as Novo Nordisk’s oral semaglutide (Wegovy) and Eli Lilly’s orforglipron, target GLP-1 alone. There was some expectation that ribupatide’s dual action – stimulating both GIP and GLP-1 receptors – might yield more substantial results. However, as Scott Wassermann, Chief Medical Officer at Kailera, noted, the phase 2 data represents an “important milestone” in developing a comprehensive treatment approach for obesity.
The study, conducted in 166 Chinese adults with obesity, showed that the 12.1% weight loss at 26 weeks did not appear to plateau, suggesting continued efficacy with longer-term use. Notably, nearly 39% of participants achieved at least a 15% reduction in body weight.
The side effect profile of oral ribupatide appears reasonably manageable. Vomiting was reported in 11.4% of participants receiving the 25 mg dose and 7.5% of those receiving 50 mg. Nausea was experienced by more than one in five patients at those doses. Importantly, the companies reported no permanent treatment discontinuations or dose reductions were required due to gastrointestinal side effects.
These findings are particularly significant given the growing demand for effective obesity treatments. Obesity is a complex chronic disease with serious health consequences and current treatment options often involve significant lifestyle changes and, increasingly, injectable medications. An effective and well-tolerated oral medication could offer a more accessible and convenient option for many patients.
Hengrui plans to initiate a phase 3 trial of ribupatide in China based on these results. Kailera is also preparing for a phase 2 international trial later this year. Kailera licensed ribupatide, along with other incretin candidates, from Hengrui in 2024 for an upfront payment of $110 million. The company is also developing KAI7535, a small-molecule GLP-1 agonist that has also demonstrated efficacy in a Chinese phase 2 study.
The positive data from Kailera and Hengrui come on the heels of similar announcements from other pharmaceutical companies. AstraZeneca recently reported topline phase 2b results with its oral GLP-1 drug, elecoglipron, further intensifying competition in this emerging market.
Wassermann emphasized the potential impact of oral ribupatide, stating, “We believe oral ribupatide could help to address the diverse needs of people living with obesity or overweight and meet patients wherever they are in their treatment journey.” He added, “These positive data suggest a potentially game-changing clinical profile for an oral obesity therapy.”
While the results are encouraging, it’s important to remember that this is phase 2 data. Larger, phase 3 trials will be crucial to confirm these findings and assess the long-term safety and efficacy of oral ribupatide. The success of these trials will determine whether this medication can ultimately become a valuable tool in the fight against obesity.
