Sopa Images | Lightrocket | Getty Images
Pfizer’The twice-daily version of the experimental diet pill has now joined a long list other scrap drugs which aimed to treat obesity but had unintended consequences.
The drug company said Friday it will stop developing the twice-daily treatment danuglipron after obese patients who received the drug lost significant weight but experienced high rates of side effects in a mid-stage clinical trial. Pfizer noted that it will publish data on a daily version of the pill next year, which will “inform the way forward.”
The announcement came six months after Pfizer withdrew a different once-daily pill in June, citing elevated liver enzymes. Pfizer’s move to abandon two obesity drug candidates in just a few months demonstrates how difficult it is to develop an effective, safe and tolerable weight loss treatment, even after the introduction of recent breakthrough drugs.
That includes Novo Nordisk‘s Wegovy and Ozempic diabetes treatment as well Eli Lillythe diabetes drug Mounjaro. All have skyrocketed in popularity—and suffered shortages—over the past year as they safely and successfully induce significant weight loss. An esteemed one 40% of US adults are obese, making these drugs the pharmaceutical industry’s newest cash cow.
But before the weight loss industry’s current gold rush, the road to treating obesity was littered with failures dating back decades.
The main reason many experimental treatments were rejected by pharmacists, rejected by US regulators or eventually withdrawn from the market was unintended side effects, such as elevated liver enzymes, cancer risks, cardiovascular risks and serious psychiatric problems such as suicide.
Eisai’s Lorcaserin
One of the latest casualties among experimental obesity drugs is a Japanese pharmacist Eisai’s lorcaserin, which was was removed off the market in 2020 due to causing an increased risk of cancer in patients.
The Food and Drug Administration green-lighted lorcaserin in 2012 based on several clinical trials, but required Eisai to conduct a larger, larger study of the drug after approval.
This study of about 12,000 patients over five years found that more people taking lorcaserin diagnosed with cancer compared to those taking a placebo, which led the FDA to withdraw the drug from the market.
Lorcaserin, marketed under the brand name Belviq, did not seem to gain much traction while it was commercially available. In its earnings for the full year 2019, Eisai mentionted that Lorcaserin had $28.1 million in US sales for the year. Worldwide sales of the drug were about $42 million. Eisai’s total sales for the year were about $4.42 billion.
Sanofi’s rimonabant
An obesity drug called rimonabant from Sanofi and Aventis was withdrawn from all markets in 2008 because of the risk of serious psychiatric problems, including suicide.
Notably, the treatment never won approval in the US because a panel of FDA experts rejected the drug amid fears it could trigger suicidal thoughts. But European regulators approved rimonabant, which is marketed under the name Acomplia, in 2006 based on extensive clinical trials.
Two years later, European regulators recommended that rimonabant be suspended after one of its panels found that the treatment’s risks—particularly psychiatric issues—were greater than its benefits.
The treatment suppressed appetite by blocking the cannabinoid receptor in the brain, which plays an important role in regulating food intake and the body’s metabolism.
Because of rimonabant’s limited time on the market and failure to win US approval, the drug never reached Sanofi’s lofty projections that it would eventually bring in $3 billion a year or more.
Sibutramine by Abbott Laboratories
Several anti-obesity drugs have also been discontinued, rejected, or withdrawn from the market because of unintended cardiovascular risks.
This includes sibutramine from Abbott Laboratorieswhich was once widely used as a treatment for obesity along with diet and exercise.
The drug was first approved in 1997 but carried warnings about high blood pressure and the risk of heart attack and stroke in cardiovascular patients.
A large, long-term trial of nearly 10,000 adults confirmed that sibutramine was associated with a significant increase in cardiovascular events, prompting regulators in the US and Europe to withdraw the drug from those markets in 2010.
Sales of sibutramine had declined before it was withdrawn from the market. The drug grossed only $80 million worldwide, including $20 million from the US, in the first nine months of 2010.
Recent evidence suggests the latest slate of approved weight-loss drugs may be having the opposite effect on heart health: Weekly Wegovy injections reduced the overall risk of heart attack, stroke and cardiovascular death by 20%, according to a recent clinical trial .