New diabetes and obesity studies making waves at EASD
As the EASD congress draws to a close, here's a round-up of some of the other clinical trials in diabetes and obesity that drew our attention.
Regeneron drug cuts muscle loss with semaglutide
Adding Regeneron's anti-GDF8/anti-myostatin antibody trevogrumab to once-weekly injectable treatment with Novo's GLP-1 agonist Wegovy (semaglutide) prevented 70% of muscle loss – a well-known side effect of incretin-based weight-loss therapy – in the phase 2 COURAGE study. There was a 7.3% loss in thigh muscle mass with Wegovy alone, which was reduced to 5.8% with a 25 mg dose of trevogrumab and 4.2% with 75 mg.
The 52-week trial also included a substudy showing that patients meeting the low lean mass definition for sarcopenia - age-related loss of muscle mass and strength - had greater loss of lean mass with standard-dose Wegovy, and more preservation with trevogrumab.
"As GLP-1 receptor agonist-based medicines become foundational to obesity care, it is becoming increasingly recognised that the associated muscle loss is an increasing concern - particularly for people with sarcopenia, older adults, and others where frailty is a real concern," said Regeneron's head of clinical development for internal medicine, Boaz Hirshberg.
"Our COURAGE trial not only confirms this concern about muscle loss, but also shows that trevogrumab can be part of the solution, addressing not the quantity, but rather the quality, of weight loss." Regeneron is planning another phase 2 trial of the antibody with GLP-1 agonists in older adults with obesity and decreased muscle mass and/or strength.
Caliway takes fat-busting drug into phase 3 after phase 2 win
Taiwan-based Caliway Biopharmaceuticals created a stir at EASD with phase 2 results for CBL-514, which works in a different way from the incretin therapies that are dominating R&D pipelines. Rather than reducing hunger and food intake, Caliway's drug is designed to destroy the fat cells that make up fat tissue by making them self-destruct, which could prevent one of the main limitations of current drugs; namely, regaining weight after they are discontinued.
The new data revealed that CBL-514 was able to reduce the volume of subcutaneous adipose tissue, with 69.6% of treated participants achieving a reduction of at least 150 mL at the eight-week follow-up point, compared with 0% of those receiving placebo. Similarly, visceral fat – a major risk factor for heart disease – fell 12% with CBL-514, but increased 5.68% with placebo, and was accompanied by improvements in blood pressure and cholesterol.
Caliway is preparing two placebo-controlled phase 3 trials of the drug as an alternative to invasive therapies like liposuction or abdominoplasty for large-area abdominal subcutaneous fat reduction, which could generate results next year.
Switch from injectables to oral Wegovy delivers more weight loss
Novo built the case for the oral formulation of Wegovy with data from the OCTANE study, which showed that patients who switched from the once-weekly injectable version of Wegovy, or Eli Lilly's GIP/GLP-1 agonist Zepbound (tirzepatide), lost another 4.1% of body weight on average in the subsequent three months.
The analysis – which draws on anonymised, real-world outcome data from 194b patients accessing Wegovy via Novo's telehealth partner Ro – also showed that the proportion of participants classified as clinically obese dropped to 65.5% from 87.1%, with nearly 41% shedding at least 5% of their body weight. They also reported treatment satisfaction and lifestyle improvements.
It's an important result for Novo, which has been falling behind Lilly in the injectable weight-loss medicine category, but remains the dominant player in the oral category, claiming a market share of around 80% in the US. It has predicted that oral drugs will eventually capture around 50% of the global market for obesity drugs as patients move away from the current weekly injectables.
Boehringer, Zealand drug works in phase 3, but tolerability a concern
Boehringer Ingelheim and Zealand Pharma's dual glucagon/GLP-1 agonist survodutide achieved a 13.1% reduction in weight in people with type 2 diabetes and overweight/obesity after 76 weeks, but the result was somewhat overshadowed by a high rate of treatment discontinuations – around 18% – due to gastrointestinal side effects.
On the plus side, more patients treated with survodutide met the target of a 5% reduction in weight compared to placebo – 79.3% versus 32.7% – and there was also a significant improvement in blood sugar control, with haemoglobin A1c biomarker levels falling 1.21% and 0.03%, respectively, from a baseline of 7.4%. The drug also achieved improvements in waist circumference and insulin sensitivity.
Earlier data readouts for survodutide also included safety signals that worried investors, and the latest reveal saw shares in publicly-listed Zealand lose around 10% of their value, although the stock subsequently regained more than half of that decline.
