- Pfizer’s twice-daily version of its experimental weight-loss pill now joins a long list of other eliminated obesity drugs.
- Pfizer’s move to scrap two obesity drug candidates last year shows how difficult it is to develop an effective, safe and tolerable weight loss treatment.
- Before successful weight-loss treatments like Wegovy and Ozempic, the path to treating obesity was riddled with decades of failure.
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Pfizer’s twice-daily version of its experimental weight-loss pill now joins a long list of other abandoned drugs that were aimed at treating obesity but had unintended consequences.
The drugmaker said Friday it was halting development of the twice-daily drug danuglipron after obese patients taking the drug lost significant weight but experienced high rates of adverse side effects in a mid-stage clinical trial. Pfizer said it will release data on a once-daily version of the pill next year that will “pave the path forward.”
The announcement came six months after Pfizer scrapped another once-daily pill in June, citing elevated liver enzymes. Pfizer’s move to drop two obesity drug candidates within months shows how difficult it is to develop an effective, safe and tolerable weight loss treatment, even after breakthrough drugs have recently come to market.
These include Wegovy and the diabetes drug Ozempic from Novo Nordisk as well as the diabetes drug Mounjaro from Eli Lilly. They have all skyrocketed in popularity over the last year – and become scarce – because they safely and successfully result in significant weight loss. An estimated 40% of adults in the U.S. are obese, making these drugs the pharmaceutical industry’s newest cash cow.
But before the weight-loss industry’s current gold rush, the path to treating obesity was littered with decades of failures.
The main reason many experimental treatments were scrapped by drugmakers, rejected by U.S. regulators, or ultimately withdrawn from the market were unintended side effects, including elevated liver enzymes, cancer risks, cardiovascular risks, and serious psychiatric problems such as suicide.
One of the latest casualties among experimental anti-obesity drugs is Japanese drugmaker Eisai’s lorcaserin, which was withdrawn from the market in 2020 because it posed an increased risk of cancer in patients.
The Food and Drug Administration gave lorcaserin the green light in 2012 based on several clinical trials, but required Eisai to conduct a larger, longer study of the drug after approval.
That study of about 12,000 patients over five years found that more people who took lorcaserin were diagnosed with cancer than those who took a placebo, prompting the FDA to remove the drug from the market.
Lorcaserin, marketed under the brand name Belviq, did not appear to have much appeal while it was commercially available. In its full-year 2019 results, Eisai reported that lorcaserin had sales of $28.1 million in the U.S. that year. Global sales of the drug were approximately $42 million. Eisai’s total revenue this year was around $4.42 billion.
An obesity drug called Rimonabant from Sanofi and Aventis was withdrawn from all markets in 2008 due to the risk of serious psychiatric problems, including suicide.
Notably, the treatment never received approval in the United States because an FDA expert panel rejected the drug out of fear that it might cause suicidal thoughts. But European regulators approved rimonabant, marketed as Acomplia, in 2006 based on extensive clinical trials.
Two years later, European regulators recommended suspending treatment with rimonabant after one of their committees found that the risks of the treatment – particularly psychiatric problems – outweighed its benefits.
The treatment suppressed appetite by blocking the receptor for cannabinoid substances in the brain, which plays an important role in regulating food intake and the body’s metabolism.
Because of Rimonabant’s limited time to market and lack of U.S. approval, the drug never reached Sanofi’s lofty forecast that it would ultimately bring in $3 billion or more per year.
Several anti-obesity drugs have also been discontinued, rejected, or withdrawn from the market due to unintended cardiovascular risks.
These include Abbott Laboratories’ sibutramine, which was once widely used to treat obesity along with diet and exercise.
The drug was first approved in 1997 but came with warnings about high blood pressure and the risk of heart attack and stroke in cardiovascular patients.
A large, long-term study of nearly 10,000 adults confirmed that sibutramine was associated with a significant increase in cardiovascular events, prompting regulators in the United States and Europe to withdraw the drug from those markets in 2010.
Sales of sibutramine had declined prior to its withdrawal from the market. The drug grossed just $80 million worldwide in the first nine months of 2010, including $20 million in the United States.
Recent evidence suggests that the newest approved weight-loss drugs may have the opposite effect on heart health: Weekly Wegovy injections reduced the overall risk of heart attack, stroke and death from cardiovascular causes by 20%, according to a recent clinical trial.