The mad rush for safe and effective obesity drugs has winners—including Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy—and losers. Here are five molecules that never made it to the market.
California-based Terns Pharmaceuticals was once a promising small player in the competitive obesity arena. Now, it’s leaving the space altogether.
The biotech made waves in September 2024 when a Phase I readout for its GLP-1 pill TERN-601 found the drug could shave 5% off of participants’ body weight after 28 days, an effect that BMO Capital Markets at the time called “compelling.” Analysts put it in the same league as Eli Lilly’s orforglipron, which has since become one of the most closely watched oral obesity candidates.
Fast-forward almost a year, however, and Terns has abandoned further investment into not just TERN-601 but its entire metabolic pipeline. Moving forward, Terns will focus on cancer, CEO Amy Burroughs announced during the company’s Q2 earnings report earlier this month. TERN-601 and its other weight-loss assets will be farmed out to potential partners.
Terns has officially dropped out of the obesity race.
Terns is hardly the first company to stumble in what has become a mad rush to claim a slice of the massive and rapidly growing obesity market, which by one estimate could reach a staggering $150 billion by 2035. Over the years, several companies, both big and small, have tried and failed to see their obesity drugs through clinical trials, tripped up by a number of issues, not least of which are safety concerns and the lack of something to set them apart in a cut-throat market.
Here, BioSpace reviews the weight-loss wasteland, focusing on five molecules that were once hailed as promising entries into the obesity arena but ultimately failed to deliver.
Danuglipron: Pfizer’s Push Stopped by Safety Issues
Arguably the most high-profile casualty of the obesity rush is Pfizer’s GLP-1 pill danuglipron, which once formed the centerpiece of the pharma’s weight-loss push.
In June 2023, Pfizer chose danuglipron over its other GLP-1 receptor agonist lotiglipron, which had shown concerning signs of liver toxicity in early- and mid-stage studies. William Sessa, who at the time was chief scientific officer of Pfizer’s internal medicine division, said that if danuglipron did well in clinical studies, it “could be in a prime position to differentiate based on profile, including full receptor agonism, which we believe has the potential to translate to robust efficacy.” Sessa left Pfizer last month, according to his LinkedIn page.
But almost immediately, danuglipron hit rough waters. In December 2023, Pfizer was forced to drop its twice-daily schedule for the drug due to side effects which, while mild and consistent with the GLP-1 class, occurred at very high rates. Up to 73% of patients in a Phase IIb study developed nausea, while more than 50% dropped out of the trial.
Still, Pfizer pushed on. In July 2024, the pharma announced that it would move ahead with a once-daily regimen of danuglipron—a decision that analysts at the time were lukewarm to. “We’re a little more cautious that this is going to turn out to be the right decision,” Guggenheim Securities’ Vamil Divan told BioSpace. Divan further speculated that this was somewhat of a Hail Mary play. “Are they just desperate and in some way [trying to] move in the [weight loss] space?”
Eventually, its toxicities caught up to danuglipron. After detecting a potential signal of liver injury, Pfizer decided to completely pull the plug on the asset in April.
Adding insult to injury, Fierce Biotech reported earlier this month that Pfizer nixed another obesity asset, the GLP-1 receptor agonist PF-06954522, officially leaving the pharma with no weight-loss candidates. A spokesperson told Fierce that the decision to scrap PF-06954522 came after a “review of data from its phase 1 program and the GLP-1 landscape,” and was not related to safety concerns.
CT-173: Roche Throws One Out From Carmot Haul
In December 2023, Roche made a bold obesity bet: The Swiss pharma dropped $2.7 billion to acquire Carmot Therapeutics, which would serve as its entry ticket into the increasingly competitive weight-loss arena.
Carmot gave Roche the centerpiece of its obesity pipeline, the subcutaneous GLP-1/GIP receptor agonist CT-388. In May 2024, just months after the buyout, the pharma released positive Phase I data for CT-388, touting an 18.8% reduction in body weight at 24 weeks versus placebo. All treated patients lost more than 5% of their weight at this time point. By July that year, Roche had gone all-in on CT-388 (as well as CT-996, another Carmot asset), with CEO Thomas Schinecker telling investors that the pharma would put its obesity assets on the “fast-track.”
But two years later, in July 2025, Roche hit a speed bump when it scrapped CT-173, also obtained from Carmot, after deciding it would not be able to compete in the current landscape. “When we bounced it up against our bar assessment, the criteria for developability and competitiveness just weren’t there,” Teresa Graham, CEO of Roche’s pharmaceuticals division, told investors at the time.
CT-173 promotes weight loss by mimicking the PYY hormone, which in the gut helps to tamp down appetite and modulate gastric motility. Preclinical data in September 2024 showed that, when used with CT-388, CT-173 helped mouse models push past weight loss plateaus while also slowing down weight rebound after treatment was stopped. In April, Roche still had plans to push CT-173 into the clinic.
Despite losing an asset, Graham in July insisted that Roche continues to have “a potentially best-in-disease and highly competitive portfolio of products” for obesity.
Roche is backing up Graham’s words with its wallet. In a deal that could top $5 billion, the pharma paid Zealand Pharma $1.65 billion upfront to collaborate on the biotech’s amylin analog petrelintide. The partners are planning to test the drug candidate as a monotherapy and as part of a combo regimen with CT-388. Zealand will also be entitled to $1.2 billion in developmental milestones plus $2.4 billion in sales-based milestones.
AMG 786: Amgen’s Little-Known Bet Cut Early
Much of the attention on Amgen’s obesity program has focused on the next-generation hopeful MariTide, a bispecific molecule that activates the GLP-1 receptor while also blocking the GIP pathway.
There is good reason for this fanfare. Amgen itself has pushed MariTide hard, with Chief Scientific Officer James Bradner telling investors in May 2024 that the pharma will “move rapidly” to advance the asset past mid-stage development and into a “broad Phase III program.”
During that same investor call, Amgen also revealed that it was scrapping its little-known, early-stage weight-loss molecule AMG 786. “In obesity, we’re differentially investing in MariTide and a number of preclinical assets,” Bradner said. AMG 786, he suggested, did not have a therapeutic profile that warranted further development.
The pharma has revealed very little about AMG 786. Amgen was running a Phase I trial for the drug, which kicked off in July 2022 and ended in August 2023. The early-stage trial enrolled 65 healthy participants and patients with obesity. The trial has been tagged as complete in a federal clinical trials database. BioSpace has reached out to Amgen to request the findings and will update this space accordingly.
Putting all of its obesity eggs in the MariTide basket may not have been the best move for Amgen, however. A Phase II readout in November 2024 left the market disappointed: After 52 weeks, the asset cut body weight by up to 20% on average, falling on the lower end of the range that investors had been expecting. Amgen crashed 11% in the aftermath, from which the pharma has only partially rebounded.
Still, Amgen is moving forward with MariTide, with the second part of this mid-stage obesity trial ongoing. Data are expected in the second half of this year, according to the company’s Q4 business report in February.
Amgen at the time also announced that its other clinical obesity asset, AMG 513, was placed on clinical hold by the FDA, though it did not say why. The pause had been lifted by the time the company reported its Q1 2025 results in May.
Azelaprag: BioAge’s STRIDES Stumbles
When BioAge Labs launched its Nasdaq bid in September 2024, it was riding a high. Just months earlier, in June, the California-based biotech presented encouraging preclinical data for its then-lead molecule, the apelin receptor agonist azelaprag.
At the 2024 meeting of the American Diabetes Association, BioAge reported that adding azelaprag to Eli Lilly’s tirzepatide approximately doubled weight loss in a mouse model of obesity and restored these animal subjects to the same body composition as lean controls. A month later, the biotech announced that it had dosed its first patient in the Phase II STRIDES study for azelaprag in obesity.
Bolstering the company’s belief in azelaprag were Phase I data, released in late 2022, which showed the molecule could help preserve muscle in patients on bed rest, indicating its potential to elicit better-quality weight loss.
BioAge had also just received a hefty $170 million infusion from its series D financing in February 2024—further validation of the market’s confidence in its pipeline, anchored by azelaprag. Some of the biggest institutional backers participated in the fundraising push, including Lilly’s venture arm. Ultimately, BioAge would close its Initial Public Offering in October 2024 with $238.3 million in gross proceeds.
Two months later, however, STRIDES hit a snag. In December 2024, the biotech discontinued the mid-stage trial after detecting liver transaminitis—elevated levels of liver enzymes suggestive of damage to, or inflammation in, the organ—in 11 patients who had been treated with azelaprag. None of the controls who were given tirzepatide alone saw this safety signal.
In January, BioAge pulled the plug on azelaprag altogether.
The biotech continues to chip away at obesity. From targeting the apelin receptor, BioAge has now pivoted to blocking NLRP3 signaling, which has been linked to chronic low-grade inflammation typical of obesity. The company’s lead NLRP3 asset, BGE-102, cleared IND-enabling studies in May with a Phase I study planned for the back half of this year and initial data by year’s end.
BI 1820237: Boehringer Ingelheim Ditches Drug From Danish Partner
Like Roche, Boehringer Ingelheim has turned to Denmark’s Zealand Pharma for help in building out its weight-loss strategy. The main outcome of this collaboration—first signed in 2011 with subsequent expansions—is survodutide, which now serves as the cornerstone of Boehringer’s obesity push.
Prior to this, in 2017, the German pharma sought help from another Danish firm to beef up its obesity pipeline. For € 250 million—worth approximately $292 million in today’s money—in upfront and success-based milestones, Hørsholm-based Gubra gave Boehringer access to a handful of novel peptide therapies for obesity, including a neuropeptide Y receptor agonist that would eventually be dubbed BI 1820237.
The partners ran a Phase I study of BI 1820237 in men with overweight, testing the injection alone or in combination with Novo Nordisk’s Victoza. Early data shared in May 2023 showed the asset lowered energy intake and slowed down gastric emptying, which Gubra at the time said supported further studies.
A readout in October 2024 seconded the additive benefits of BI 1820237 on top of Victoza, but also recorded high rates of toxicities: 39% of treated patients experienced side effects, most of which were gastrointestinal in nature, including nausea and vomiting.
That same month, Boehringer opted to terminate development of BI 1820237, according to an announcement from Gubra, which did not reveal the specific reason for the discontinuation. Three other programs under the 2017 pact, including one potentially first-in-class triple agonist for obesity, are ongoing.
Boehringer’s survodutide push appears to be going better. The GLP-1/GCCR dual agonist is currently in late-stage development for obesity and metabolic dysfunction-associated steatohepatitis. SYNCHRONIZE-1 and SYNCHRONIZE-2 in obesity were both launched in 2023, with completion dates next year.
