Pfizer announced on Friday (Dec 1) that it’s dropping development of an experimental weight-loss pill after patients experienced uncomfortable side effects in clinical trials.

A pill has been widely viewed as a way for new players to make inroads in a frenzied new weight-loss market dominated by the makers of shots Ozempic and Mounjaro. Some potential patients may find themselves a bit squeamish about the idea of sticking themselves with a needle.

A pill has also proved to be especially challenging to make. Shots made by Eli Lilly & Co. (Mounjaro, Zepbound) and rival Novo Nordisk A/S (Ozempic, Wegovy) have become a veritable gold mine, one projected to reach US$100 billion within the next seven years. But other drugmakers have struggled to find a foothold in the market. A weekly jab to the stomach or thigh may not seem like the most desirable delivery mechanism for a drug, but so far it’s the most effective. In trials, patients who received the highest dose of Lilly’s Zepbound lost on average 18 per cent of their body weight. Some drugs earlier in development rival a level of weight loss only thought possible with bariatric surgery.  

A pill might persuade more patients to take weight-loss drugs. They’re enticing for drugmakers, too. Pills are generally easier to make, store and transport than injections, once the right formulation is discovered. But they’re also a much more difficult scientific problem to solve. Even Lilly and Novo have struggled to make pills that work as well as injections. 

The new pills aim to mimic GLP-1, a hormone that makes people feel full. So far though, they’ve had limitations. Rybelsus, Novo’s pill version of the diabetes shot Ozempic that’s often used for weight loss, is already available at US$936 for a one-month supply. But it’s not nearly as effective for weight loss as the shot: In studies, diabetic patients on the highest dose of Rybelsus lost just 8 pounds. People with type 2 diabetes lost almost twice that with Ozempic.

Novo is testing a higher-dose pill specifically for weight loss that could be approved as soon as next year, but patients must take it daily on an empty stomach – as opposed to a weekly injection – and then must wait another half hour before eating. More gastrointestinal side effects were reported in trials of the pill than in studies of Wegovy injections. 

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The Rybelsus pill also requires significantly more active ingredient than shots, and that substance, semaglutide, is already in short supply. Lilly’s experimental pill doesn’t have the same restrictions as Novo’s when it comes to timing and food intake, but it’s further behind in development. It’s likely still years away from being commercially available.

Pills like Pfizer’s that are small molecule drugs may generally pose a higher risk for side effects, experts say. “We note a fundamentally different metabolism between small molecule-based GLP-1 agonists,” such as Pfizer’s drug versus peptide-based drugs like Novo’s, Truist analyst Joon Lee said in a note. Risk of liver toxicity could be much higher with small molecules, he said.

It was a risky bet for Pfizer to start with a pill, which has shown to be far more difficult to develop than the shots. Pfizer’s pill, danuglipron, was meant to be taken twice daily. In a mid-stage trial, nearly three-quarters of patients experienced nausea, nearly half experienced vomiting and an much as a quarter experienced diarrhea, numbers the company felt were too high to convince people to take its drug twice every day. It hasn’t yet given up hope for a pill, though. The company will continue with efforts to develop a once-daily version of the pill.

On Friday, the company said in a statement that the outcome of the trial will “inform a path forward.” Rival drugmaker AstraZeneca Plc also has an obesity pill in the works. 

The weight loss market is only just getting started, with more and more drugmakers looking to get in on the action. Pills are the next big thing, but it may still be years until we have ones that can rival shots. BLOOMBERG