Roche data shows stomach-churning side effects of weight-loss drugs

Roche raised hopes this year that it had a future blockbuster drug on its hands after early trial results of the Swiss pharmaceutical group’s new obesity treatments showed rapid weight loss among recipients.

But revelations earlier this week of high rates of vomiting and other side effects among those who took strong doses of the drugs have unsettled investors and highlighted the challenges facing businesses that want to enter the lucrative new market for “GLP-1” drugs.

The company’s shares dropped 4 per cent on Monday after it revealed that three-quarters of patients on the highest dose of its CT-388 injection had suffered from vomiting. They fell another 5 per cent on Thursday after similar data for its oral weight-loss pill.

The reaction is a reminder that not all patients can tolerate the new class of weight-loss treatments dominated by Novo Nordisk and Eli Lilly — and that challengers to the industry’s pioneers face significant hurdles.

The treatments were one of the main talking points at the conference of the European Association for the Study of Diabetes in Madrid this week.

Peter Verdult, a Citigroup analyst attending the conference, said Roche had caused problems for itself by touting its initial trial results in July as “really special data”.

“I don’t think anyone can say that now,” he said. “They set themselves up for a fall.”

Global drugmakers are racing to catch up with Novo Nordisk and Eli Lilly’s lead in the lucrative and rapidly growing GLP-1 drug market.

Of the 1,150 research abstracts presented at the Madrid conference, almost one-10th featured GLP-1 drugs.

The medication has proved an effective way both to control weight and treat diabetes, and Goldman Sachs analysts have estimated the market for the products could grow to $130bn annually by 2030.

The novel drugs work by mimicking the gut hormone GLP-1, which lowers blood sugar and limits the appetite. Treatments such as Eli Lilly’s Mounjaro also add another gut hormone, GIP, that appears to enhance weight loss. In addition, companies are experimenting with other gut and pancreatic hormones.

Francine Kaufman, a former head of the American Diabetes Association and now chief medical officer of medical devices company Senseonics, said the drugs had revolutionised diabetes care at a moment when obesity rates were rising.

“I said in the 2000s that we needed a silver bullet,” she said. “It arrived.”

GLP-1-based drugs are, nevertheless, associated with vomiting, nausea and constipation, particularly in higher doses. They are also linked with muscle wastage in some trials. The US Food and Drug Administration and the European Medicines Agency have explored other more serious side-effects reported with recent drugs — such as suicidal thoughts — but found no evidence of a link.

Defending the potential of Roche’s drugs, Manu Chakravarthy, who leads the company’s metabolic product development, said it had wanted to “push the tolerability” of its drug and that side-effects at high doses were consistent with other GLP-1-based drugs.

Users of Roche’s products in future trials were unlikely to receive such high doses or rapid increases, Chakravarthy added.

“We’re encouraged as it cannot get any worse than this,” he said.

Drugmakers use early trials to test the safety of their drugs and often test high doses. Verdult said there were also concerns about side-effects years ago when Novo Nordisk and Eli Lilly presented data on their drugs.

At the Madrid conference, Novo Nordisk presented data on a new drug — oral amycretin — showing it prompted vomiting in more than half of users on the highest dose.

The side-effects appear to deter some patients. Research published this year by Blue Health Intelligence found that 30 per cent of GLP-1 users stopped treatment within four weeks of starting, with side effects a significant factor. Cost and availability of the drugs are also a factor.

Former UK prime minister Boris Johnson wrote in a Daily Mail newspaper column last year that he was unable to tolerate vomiting linked to taking diabetes treatment Ozempic off-label.

Other drugmakers have had setbacks in developing so-called small molecule pills — synthetic drugs that are easier to manufacture at scale than weight-loss injections.

Pfizer abandoned a twice-daily version of its weight-loss drug danuglipron after recording a high degree of nausea and vomiting in mid-stage trials. But the New York-based drugmaker is pushing ahead with a daily, tweaked version.

To tackle side effects, companies are developing alternative formulations of drugs. Analysts noted excitement about amylin, a pancreatic hormone that is thought to reduce muscle wastage linked to drugs, although this has yet to be proved at scale.

Novo Nordisk’s next product — CagriSema — combines GLP-1s with an amylin analogue. The drugmaker will report late-stage data later this year from the product.

Eli Lilly has struck several deals aimed at resolving the issue of muscle wastage. Last year it spent up to $1.9bn acquiring Versanis, whose lead drug is based on the hormone activin that helps to regulate muscle mass. It is also partnering with BioAge, a company developing a muscle regeneration drug. BioAge recently filed for an initial public offering.

Yet the emerging data continues to underline how much companies, investors and scientists still have to discover about how GLP-1 treatments work.

Among the studies presented in Madrid was one that showed Eli Lilly’s Mounjaro drug led to more effective weight loss among women than men but also caused higher rates of nausea and vomiting.

Luis-Emilio García-Perez, the Eli Lilly scientist who undertook that study, said the company did not know why the results differed between the two groups.

Ilya Yuffa, Eli Lilly’s head of international operations, said it was still unclear whether new treatments would have fewer side effects and would allow the anticipated broad take-up of the drugs.

“For the other molecules that are in development that may have new approaches, I think it’s probably too early to have a clear view of what they look like in broader populations,” said Yuffa.