番茄社区

On June 4, 2021, 番茄社区 first reported on the "game changing" approval of the GLP-1 receptor agonist semaglutide 2.4 mg (Wegovy) for chronic weight management. As part of our review of the year's top stories, we follow up on what has happened since this approval.

The FDA approved the GLP-1 receptor for chronic weight management in adults with obesity (BMI of 30 or greater) or for adults with overweight (BMI 27 or greater) plus at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol, used in conjunction with a reduced calorie diet and an exercise regimen.

As the first drug approved for this indication since 2014, the greenlight for semaglutide was quickly met with a wave of enthusiasm from the healthcare community.

"Wegovy will likely be the first of a few up-and-coming agents that will help close the treatment gap between anti-obesity medications and bariatric surgery," said Caroline M. Apovian, MD, of Brigham and Women's Hospital in Boston, in a . "This new agent provides nearly double the weight loss (10 to 20%) as current agents on the market (5 to 10%) inching closer to the robust weight loss of 25 to 30% seen with bariatric surgery."

Part of the excitement over this new agent was the impressive weight loss it demonstrated in the Semaglutide Treatment Effect in People with Obesity (STEP) clinical program, underpinning its FDA approval. One of the installments in this program -- the STEP 1 study -- showed an average 14.9% of baseline body weight loss after 68 weeks of treatment versus only 2.4% for a group on placebo and lifestyle intervention alone among adults with a BMI of 30 or more.

"I was surprised and gratified to see the unprecedented results from the medication," lead trial investigator Robert Kushner, MD, of Northwestern University Feinberg School of Medicine in Chicago, previously told 番茄社区. "The fact that 50% of participants were able to lose at least 15% of initial body weight and one-third lost at least 20% body weight is a game changer."

And in the STEP 2 trial, the once-weekly 2.4 mg injectable semaglutide also demonstrated significant weight loss for people with a BMI of at least 27 and comorbid type 2 diabetes.

Following its approval, came to the fore. At a monthly wholesale cost around $1,350, 20 years of treatment could total over $323,000. This runs about 58% lower than the cost of the semaglutide pens used in type 2 diabetes (Ozempic) despite containing more than double the dosage of semaglutide as Ozempic.

This steep price didn't seem to deter patients or prescribers, as after hitting the market shortly after its June approval. But this initial demand for the new weight loss drug even seemed to have "exceeded supply," , which could have led to some delays in prescriptions being filled. Despite these potential stocking concerns early on, manufacturer Novo Nordisk's president and CEO Lars Fruergaard Jørgensen said in the fall that it "significantly exceeded [Novo Nordisk's] expectations, underscoring the high unmet need for people living with obesity."

With this commercial success, the company expanded the development pipeline. A 50-mg oral version of semaglutide is in the works for chronic weight management, based off of the oral formulation of semaglutide (Rybelsus) used at doses of 7 and 14 mg for type 2 diabetes.

And by November, yet another installment in the STEP clinical program was unveiled at the virtual ObesityWeek 2021 meeting. In that , semaglutide showed sustained weight loss over a 2-year period. Compared with placebo, those on active treatment plus diet and exercise saw a 12.6% greater reduction from baseline body weight by week 104.

"People with obesity try on average seven times to lose weight before seeking medical care. Once weight is lost, however, it all too often comes back, which is why it is critically important to find options to help people living with obesity lose weight and keep it off," said W. Timothy Garvey, MD, of the University of Alabama in Birmingham, in a statement. "Results from the STEP 5 clinical trial demonstrated that adults with obesity were able to lose weight while taking Wegovy and maintain the weight loss at two years, which can help us better treat and manage obesity as a chronic disease."

In late December, though, . A contract manufacturer filling the syringes for semaglutide temporarily stopped manufacturing and delivering product to the U.S. market.

"As a consequence, Novo Nordisk does not expect to be able to meet demand in the US in the first half of 2022 and few new patients are expected to be able to initiate treatment," read a statement from the company. It added that the priority will go towards patients who have already initiated treatment. This kink in the U.S. supply chain also isn't expected to be fully resolved until the second half of 2022.

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