Designers of anti-obesity drugs have suffered three major setbacks, but the potential reward from treating the world’s fat epidemic is so great that their quest is unlikely to be deterred.
After investing a sum rumored to be in the hundreds of millions of euros, Sanofi-Aventis of France announced this month it was abandoning its drug rimonabant, which had stoked huge expectations at its launch in 2006.
Rimonabant — brand name Acomplia — ran into a flurry of ever-tougher warnings from European watchdogs about potential psychiatric side effects, including depression.
Last month, the European Medicines Agency (EMEA) recommended that rimonabant be pulled from sale in Europe. The drug had never been able to gain approval in the all-important US market.
Also this month, the US giant Pfizer put a stop to tests of a prototype in late-stage development called CP-945,598, citing regulatory hurdles.
“The risk/benefit profile in this class of drugs was lower than expected for obtaining market authorization,” said Catherine Baulac, in charge of new products with Pfizer’s French subsidiary.
And on Oct. 2, Merck of the US pulled the plug on its own experimental obesity fighter, taranabant, because of concerns about anxiety and depression at high doses.
The main causes of obesity — overconsumption of fatty or sugary food and a sedentary lifestyle — are well known. But the molecular machinery that drives it is in many ways obscure and it is now suspected, more complex than thought.
Treating obesity entails a limited basket of options, from lifestyle changes to drugs and gastric-bypass surgery.
But when it comes to that middle choice, the most promising class of new prescription medicines for treating long-term obesity has just been wiped out.
The three scratched drugs belong to a group called cannabinoid receptor antagonists.
They take on the same target in the central nervous system as marijuana. But instead of sharpening appetite — the “munchies” associated with smoking cannabis — they work in reverse, dulling the urge to eat.
“There are now just two drugs left, orlistat and sibutramine,” said Colin Waine, a doctor who is chairman of a British organisation, the National Obesity Forum.
Anders Sjoedin, a specialist in obesity drugs at the University of Copenhagen, Denmark, said cannabinoid receptor antagonists had now been discredited as an approach.
“Cannabinoid receptors not only regulate the appetite, they also affect mood,” he said.
Orlistat, marketed as Xenical or alli, curbs absorption of fat in the intestine by blocking a pancreatic enzyme. Sibutramine, sold as Reductil or Meridia, affects levels of a brain chemical called serotonin, believed to influence feelings of hunger or satiety.
Both are “very useful,” Waine said.
But they come with a list of side effects, including, in orlistat’s case, the risk of sudden, oily feces. As proof of the glittering allure of the obesity market, drug engineers are exploring unusual paths.
The WHO said around 400 million adults were obese in 2005, and the tally is expected to balloon to more than 700 million in 2015.
In the lab, at least, are potential rivals to orlistat in the field of lipase inhibitors, new neurotransmitter inhibitors that reduce appetite and even a hydrogel pill that expands in the stomach to give a sense of fullness.
But, should these prototypes ever get the green light to go on sale, will they meet the hopes of people desperate to lose dozens of kilos in a year rather than just a few? Even more important, are they safe?
Eleven years ago, the search for an obesity drug ran into controversy when fenfluramine, an appetite suppressant, was banned in the US over fears of its effect on the heart. This month, a study published in the journal BioMed Central found fenfluramine’s damage to cardiac valves was visible seven years later.
Archeologists in Peru on Thursday said they found the 5,000-year-old remains of a noblewoman at the sacred city of Caral, revealing the important role played by women in the oldest center of civilization in the Americas. “What has been discovered corresponds to a woman who apparently had elevated status, an elite woman,” archeologist David Palomino said. The mummy was found in Aspero, a sacred site within the city of Caral that was a garbage dump for more than 30 years until becoming an archeological site in the 1990s. Palomino said the carefully preserved remains, dating to 3,000BC, contained skin, part of the
‘WATER WARFARE’: A Pakistani official called India’s suspension of a 65-year-old treaty on the sharing of waters from the Indus River ‘a cowardly, illegal move’ Pakistan yesterday canceled visas for Indian nationals, closed its airspace for all Indian-owned or operated airlines, and suspended all trade with India, including to and from any third country. The retaliatory measures follow India’s decision to suspend visas for Pakistani nationals in the aftermath of a deadly attack by shooters in Kashmir that killed 26 people, mostly tourists. The rare attack on civilians shocked and outraged India and prompted calls for action against their country’s archenemy, Pakistan. New Delhi did not publicly produce evidence connecting the attack to its neighbor, but said it had “cross-border” links to Pakistan. Pakistan denied any connection to
TRUMP EFFECT: The win capped one of the most dramatic turnarounds in Canadian political history after the Conservatives had led the Liberals by more than 20 points Canadian Prime Minister Mark Carney yesterday pledged to win US President Donald Trump’s trade war after winning Canada’s election and leading his Liberal Party to another term in power. Following a campaign dominated by Trump’s tariffs and annexation threats, Carney promised to chart “a new path forward” in a world “fundamentally changed” by a US that is newly hostile to free trade. “We are over the shock of the American betrayal, but we should never forget the lessons,” said Carney, who led the central banks of Canada and the UK before entering politics earlier this year. “We will win this trade war and
Armed with 4,000 eggs and a truckload of sugar and cream, French pastry chefs on Wednesday completed a 121.8m-long strawberry cake that they have claimed is the world’s longest ever made. Youssef El Gatou brought together 20 chefs to make the 1.2 tonne masterpiece that took a week to complete and was set out on tables in an ice rink in the Paris suburb town of Argenteuil for residents to inspect. The effort overtook a 100.48m-long strawberry cake made in the Italian town of San Mauro Torinese in 2019. El Gatou’s cake also used 350kg of strawberries, 150kg of sugar and 415kg of
RSS