Pinned straw:
another data point in the whole GLP saga, from the FT.
The success of Novo’s bestsellers Ozempic and Wegovy has created a gold rush in the pharma industry © Bloomberg
The co-founder of Regeneron has warned that blockbuster weight-loss drugs could cause “more harm than good” unless the rapid muscle loss associated with the treatments is solved, as the US biotech pushes ahead with trials of muscle-preserving medicines.
Clinical studies suggest that patients treated with the new class of weight- loss drugs, known as GLP-1s, lose muscle at far faster rates than people losing weight from diet or exercise, exposing them to health problems, said George Yancopoulos, who also serves as Regeneron’s chief scientific officer.
For the two in every five patients who discontinue the treatments within a year, according to a 2024 JAMA study, this means that they are likely to rebound to their original weight with less muscle and a higher body fat percentage, “adding insult to injury”, said Yancopoulos.
“I do think that the GLPs should be viewed with a lot of concern in terms of the way they’re actually being used in the real world,” said Yancopoulos. “They could be leading to successive changes in body composition that could be creating more harm than good in the long term.”
Regeneron is among a growing list of drugmakers researching experimental drugs to preserve lean muscle mass in combination with GLP-1 drugs as a route into a potentially $130bn-a-year market that is dominated by Ozempic and Wegovy maker Novo Nordisk and Eli Lilly, the company behind Mounjaro and Zepbound.
Regeneron, a $111bn biotech that specialises in antibody treatments, is testing a drug called trevogrumab, which blocks the hormone myostatin, which limits muscle growth, in combination with Wegovy in mid-stage trials. There are 11 myostatin drugs in biotech pipelines, of which seven are being investigated for obesity, according to industry tracker Citeline.
Last year, Eli Lilly bought Boston-based biotech Versanis in a deal worth $1.9bn to get its hands on its muscle-preserving treatment to complement its weight-loss drugs. BioAge, a biotech with a muscle-regeneration drug that is partnered with Eli Lilly, listed last month and its share price is up 21 per cent.
Clinical data shows that 25 per cent of weight loss from Eli Lilly’s shot resulted from a reduction in lean body mass, including muscle, while 40 per cent of Novo Nordisk’s jab was due to a drop in lean body mass.
The US Food and Drug Administration advises that the drugs be used in combination with diet and exercise. Novo Nordisk said clinical data “[does] not indicate an association of greater lean body mass loss over fat mass loss with semaglutide treatment”. Eli Lilly did not immediately respond to a request for comment.
The first clinical data from Regeneron’s phase-two trial of trevogrumab is expected halfway through next year. Regeneron is also considering whether to advance a monthly GLP-1 injection to clinical trials, which it has tested in mice. Despite his concerns about the drug, Yancopoulos said Regeneron was “thinking about becoming players in the GLPs”.
“I’m not sure that the GLPs are really the true final answer here, because they could have significant long-term problems,” he added.
“We all want to have 10 more pounds of muscle, 10 less fat, but we could eat whatever we want — that’s the ideal world,” said Yancopoulos.
“We don’t all want to be nauseous and sick and losing muscle. I do think that . . . an ideal future is one where we achieve a better, healthier way of fighting back against metabolic disease.”
In my day job as an anaesthesiologist in a community with high levels of obesity, I meet a lot of patients who have OSA. Probably only about a quarter routinely use their CPAP, and these are the people who feel tired during the day due to poor quality sleep, can afford the devices, and tolerate the masks.
Probably another quarter give up on their CPAP because they dont like the mask. Another quarter know or suspect they have OSA, and are in denial about their health, dont want the stigma of the mask, or dont care because they don't feel particularly tired and don't have anyone nagging them about their snoring. The final quarter are oblivious to the diagnosis, but its clear to me when I see them sleep.
Out of this population, the 25% of people who cant tolerate or dont want a CPAP device are the ones most likely to seek an alternative treatment such as tirzapetide / other GLP1s / weight loss surgery. This group were unlikely to become CPAP customers at all. Meanwhile, the other 50% of patients who are unaware or unmotivated to treat OSA, may become users of GLP1s, but may or may not have ever become a CPAP user.
It really is clear to me that CPAP and GLP1s are complementary therapies, with some overlap and more co-creation of value than erosion/competition.