Pfizer weight reduction capsule joins record of weight problems drug flops

Pfizer’s twice-daily model of its experimental weight loss pill has now joined a protracted record of other scrapped drugs that aimed to deal with weight problems however got here with unintended penalties. 

The drugmaker on Friday mentioned it’s going to cease growing the twice-daily remedy, danuglipron, after overweight sufferers taking the drug misplaced important weight however skilled excessive charges of adversarial unwanted effects in a midstage scientific trial. Pfizer famous that it’ll launch knowledge on a once-daily model of the capsule subsequent yr, which can “inform the path forward.” 

The announcement got here six months after Pfizer scrapped a special once-daily capsule in June, citing elevated liver enzymes. Pfizer’s transfer to drop two weight problems drug candidates in just some months demonstrates how tough it’s to develop an efficient, secure and tolerable remedy for losing a few pounds, even after current breakthrough drugs entered the area. 

That features Novo Nordisk‘s Wegovy and diabetes remedy Ozempic in addition to Eli Lilly‘s diabetes drug Mounjaro. They’ve all skyrocketed in recognition — and slipped into shortages — over the past yr for safely and efficiently inflicting important weight reduction. An estimated 40% of U.S. adults are overweight, making these medicine the pharmaceutical business’s latest money cow. 

However earlier than the present weight reduction business gold rush, the trail to treating weight problems was strewn with failures courting again a long time.

The principle purpose many experimental therapies have been scrapped by drugmakers, rejected by U.S. regulators or ultimately pulled from the market have been unintended unwanted effects, together with elevated liver enzymes, most cancers dangers, cardiovascular dangers and critical psychiatric issues, resembling suicide. 

Some of the current casualties amongst experimental weight problems medicine is Japanese drugmaker Eisai’s lorcaserin, which was removed from the market in 2020 because of inflicting an elevated danger of most cancers in sufferers. 

The Meals and Drug Administration greenlit lorcaserin in 2012 primarily based on a number of scientific trials however required Eisai to conduct a bigger and longer examine on the drug after the approval.

That examine on about 12,000 sufferers over 5 years discovered that extra folks taking lorcaserin have been diagnosed with cancer in contrast with these taking a placebo, which led the FDA to tug the drug from the market.  

Lorcaserin, marketed beneath the model title Belviq, did not seem to achieve a lot traction whereas it was commercially out there. In its full-year 2019 earnings, Eisai reported that Lorcaserin had gross sales of $28.1 million within the U.S. for the yr. International gross sales of the drug have been about $42 million. Eisai’s whole gross sales for the yr have been roughly $4.42 billion.

An weight problems drug referred to as rimonabant from Sanofi and Aventis was withdrawn from all markets in 2008 because of the danger of great psychiatric issues, together with suicide. 

Notably, the remedy by no means gained approval within the U.S. as a result of a panel of consultants to the FDA rejected the drug amid fears that it might trigger suicidal ideas. However European regulators accepted rimonabant, marketed beneath the title Acomplia, in 2006 primarily based on in depth scientific trials. 

Two years later, European regulators advisable the suspension of rimonabant after one among its committees decided that the dangers of the remedy — significantly psychiatric points — outweighed its advantages. 

The remedy suppressed urge for food by blocking the receptor of cannabinoid substances within the mind, which performs an vital position in regulating the physique’s meals consumption and metabolism. 

Attributable to rimonabant’s restricted time in the marketplace and failure to win U.S. approval, the drug by no means reached Sanofi’s lofty projection that it might ultimately generate $3 billion a yr or extra. 

That features sibutramine from Abbott Laboratories, which was as soon as extensively used as a remedy for weight problems together with food plan and train.

The drug was first accepted in 1997, however carried warnings about hypertension and a danger of coronary heart assault and stroke in cardiovascular sufferers. 

A big, long-term trial on practically 10,000 adults confirmed that sibutramine was related to a major improve in cardiovascular occasions, which prompted regulators within the U.S. and Europe to tug the drug from these markets in 2010.

Gross sales of sibutramine had been dwindling forward of its removing from the market. The drug raked in solely $80 million globally, together with $20 million from the U.S., within the first 9 months of 2010.

Latest proof means that the latest slate of accepted weight reduction medicine might have the alternative impact on coronary heart well being: Weekly injections of Wegovy slashed the general danger of coronary heart assault, stroke and loss of life from cardiovascular causes by 20%, based on a recent clinical trial.