The Japanese biotech company behind Eli Lilly's breakthrough oral obesity medication is positioning itself to revolutionize weight loss treatment by combining its licensed drug with an anti-muscle wasting therapy it has developed in-house.
Hitoshi Iikura, a senior executive at Chugai Pharmaceutical, told the Financial Times that the company has "high expectations" for combining its muscle preservation drug with orforglipron, the once-daily obesity pill licensed to Lilly, or similar treatments. This strategic approach aims to address muscle loss, a common side effect of current obesity medications.
Addressing Critical Treatment Gap
Chugai, majority-owned by Roche, originally developed GYM329 for treating degenerative muscle loss in spinal muscular atrophy (SMA). However, research indicates that loss of "lean mass," which includes muscle tissue, can represent 25-39% of total weight loss in patients taking modern obesity drugs. Maintaining muscle mass is crucial for overall health, particularly as patients age.
"In the case of GYM329, it expanded to obesity treatment, which is a broader application than we initially expected," Iikura explained. "Now we have high expectations for that."
Market Success Drives Innovation
Chugai's success with novel drugs, particularly orforglipron, has driven its stock price to all-time highs this year, making it the 11th largest company on the Tokyo Stock Exchange in April when orforglipron passed a significant milestone. Late-stage trial results demonstrated that the drug reduces weight and blood sugar while maintaining safety levels comparable to injectable treatments, including Wegovy, Ozempic, and Lilly's Zepbound and Mounjaro. The medication is expected to reach market next year.
Stephen Barker, an analyst at investment bank Jefferies, estimates orforglipron could generate $40 billion in annual sales at its peak, highlighting the enormous market potential.
Strategic Development Approach
Iikura emphasized that the company did not initially set out to cure obesity. The focus on weight loss became possible as Chugai's scientists selected research targets that offered opportunities for developing drugs with broader applications than originally anticipated.
Chugai employs a "monozukuri" approach of precision and perfectionism in researching molecules and antibodies, while benefiting from Roche's involvement in covering late-stage clinical trial costs. The company's operating profit margins of 48% last year rank among the highest in the industry.
Partnership Dynamics and Market Position
Following a 2002 deal with Roche, the Swiss group holds first refusal rights on all Chugai drugs. Hemlibra, a hemophilia treatment developed by Chugai, became Roche's second-largest seller and dispelled investor concerns about the partnership.
However, Roche declined orforglipron after a difficult previous experience with obesity treatment. While Novo Nordisk and Lilly had long tested treatments for diabetes-related metabolic diseases, the rest of the industry showed little enthusiasm until recently.
Eli Lilly acquired orforglipron from Chugai for an upfront payment of $50 million, plus milestone payments and ongoing royalties.
Research Timeline and Future Prospects
Chugai began orforglipron research around 2003, according to Hiroshi Kawabe, who leads the research and development team. The goal was to improve diabetes drugs in trials at the time, making them longer-acting, more stable, and deliverable as tablets.
"Since 2018, the market and scientific options have developed significantly and a new generation of drugs has been developed for obesity treatment," Roche stated. In 2023, the company decided to return to obesity drug development.
Analysts note that combining orforglipron and GYM329, which is licensed to Roche, remains in early stages, as some researchers remain skeptical about muscle loss risks from anti-obesity drugs.
Miki Sogi from Bernstein observed that "if this combination becomes the standard of care for patients with obesity, then that would be huge," underscoring the potential transformative impact of this therapeutic approach.
