If you’re feeling like overnight obesity became the indication du jour, you’re not alone.
Novo Nordisk was granted approval for semaglutide to be marketed as Wegovy for chronic weight management in June 2021, after being sold for diabetes as Ozempic. Then came Eli Lilly in the fall of 2023 with the approval of tirzepatide as Zepbound, which is also marketed for diabetes as Mounjaro.
Now, pharma has gone all in, creating a robust pipeline of meds that will define the sector’s next few decades. Industry data provider IQVIA pulled together a list of the current obesity pipeline, which features 124 medicines altogether: 61 in phase 1, 47 in phase 2, eight in phase 3 and eight on the market.
“Most innovation is incremental. Most things are a percent better than what came before,” IQVIA Lead Research Director Michael Kleinrock said in an interview with Fierce Biotech. “What’s interesting and notable here, when you see these medicines from Novo [and] Lilly, the ones that are emerging here in the GLP-1 cluster particularly, are significantly higher degrees of weight loss than what had come previously.”
The industry has seen a pharmaceutical weight loss frenzy before to pretty disastrous results with the 1990s rise of fen-phen, which was prescribed to millions of Americans before ultimately being found to be harmful. What’s different this time around is the efficacy and validated safety of the GLP-1 drugs and the switch in messaging: This is about improving health, not necessarily losing weight for cosmetic reasons.
“We have for 25 years been in a situation where whatever obesity medicines emerge from research are generally less well accepted in the commercial market,” said Kleinrock. “So we’ve had all sorts of high hopes.”
Those hopes have always ended up being underwhelming in terms of the weight loss achieved and the money ultimately made on the market. Until now.
Another thing that has been surprising about the rise of GLP-1s is that they didn’t follow the traditional phase 1 through 3 clinical trajectory. In fact, the weight loss benefits of GLP-1s became known in the context of their use in diabetes. That means the pipeline as we see it now—with just eight phase 3 meds—could suddenly get a lot fuller without drugs moving through the earlier stages as usual.
“The obesity outcomes are late breaking, and the drugs are already approved for something else and then suddenly, the obesity outcomes just plop on your desk,” Kleinrock said. That kind of breaking research news “sneaks up on people,” he added.
For that reason, he was surprised by the sudden acceleration of phase 1 starts with brand-new, never before seen drugs entering human testing.
It’s still early days for most of that phase 1 pipeline, which account for 61 (52%) of the 116 total assets currently in phase 1 through 3 development. Several Big Pharmas are trying their hand in the space, with names like AstraZeneca, Bristol Myers Squibb, Novartis and Amgen touting early-stage assets in obesity.
While Novo, and soon to be Lilly, have a tight grip on the market, they will face tough competition in the years to come. What’s already clear, though, is that GIP/GLP agonists are the future.
Kleinrock likens the obesity rush to what happened with PD-1 inhibitors in oncology. Once an effect was seen, companies raced into the space. But, ultimately, the clinic winnowed out the also-rans until only the strongest meds advanced.
“There’s a lot going on. How many do you see ultimately in a stable market for obesity 10 years from now? It’s not 124,” Kleinrock said.
He suspects GLP-1s aren’t going anywhere for the indication any time soon. He calls them the “alpha dog” of the therapy group. But “not every launch has to pass number one to be on the market,” he added.
The baselines are already being set. Viking Therapeutics’ dual GLP-1 and GIP agonist produced weight loss of up to 14.7% after 13 weeks of treatment in data released in February. The results were competitive to the Big Pharma heavyweights.
While the early-stage pipeline cruises along, Novo and Lilly aren’t wasting any time. Earlier in March, Wegovy was granted approval to reduce the risk of cardiovascular death, heart attack and stroke in adult patients with cardiovascular disease who have obesity or are overweight.
And Lilly showcased data in metabolic dysfunction-associated steatohepatitis (MASH) for tirzepatide. The therapy helped 74% of overweight or obese adults with MASH clear the disease with no worsening of liver scarring, or fibrosis, after 52 weeks.
Besides improving on the actual weight loss that can be achieved with the incretin meds, companies are working fast to create oral forms of the medicines, too. According to IQVIA’s analysis, the drug development field is 50% subcutaneous delivery and 46% oral. While the market is anxiously waiting, Kleinrock said these studies are necessarily very large and need a lot of follow-up to confirm efficacy, so they will be slow to advance.
“Imagine an obesity landscape years from now, where you have highly potent medicines for an initial treatment and a different group of medicines for maintenance,” he said.
The market is also severely restrained by patients’ ability to pay. Right now, U.S. insurers are for the most part not covering Wegovy or Zepbound for obesity, meaning access to treatment is restricted to those who can pay. Kleinrock sees this as a huge problem. Patients that may need the drugs the most—people who are morbidly obese and on Medicaid, for example—likely can’t afford them. Medicare is currently legally forbidden from covering the drugs, too.
“The societal burden of obesity doesn’t nicely land on people who can afford these therapies, as wonderful clinically as they appear to be,” Kleinrock said. “For me, the question is not necessarily how enthusiastic investors and the innovative companies are, and how thrilled their shareholders may well be, but from our current position of not managing obesity terribly well at all, where will we be in a few years?”
In cancer, patients with the most severe disease get access first, before the advancements move to standard of care in earlier lines of therapy. What does that mean in the context of obesity?
“Whether these 124 research options are part of that, creating competition and creating a market dynamic that enables payers to feel comfortable to pay for these,” Kleinrock said, “those are questions.”