Retatrutide

Happy Saturday, and welcome back to Endpoints Weekly. Our senior biopharma journalist Elizabeth Cairns covered a flurry of readouts this week from Eli Lilly and Novo Nordisk. We’ve summarized the data below, as well as Elizabeth’s thoughts on how Novo Nordisk might navigate what Jefferies managing director Michael Leuchten called a “strategic conundrum.” Keep reading for John Carroll’s breakdown on the top 100 venture investors in biotech, plus more details on Doug Ingram’s decision to step down from Sarepta and the end of Roctavian’s commercial saga. Endpoints’ Max Bayer and Zachary Brennan also reported this week that the FDA is using an outside investigator to look into complaints against CBER Director Vinay Prasad. And don’t forget to submit your nominations to Endpoints’ fifth annual LGBTQ+ Leaders in Biopharma special report. Nominations are due by March 25. — Nicole DeFeudis It was a busy week for Eli Lilly and Novo Nordisk. Things kicked off with news about CagriSema, Novo’s GLP-1 plus amylin therapy. The Danish pharma company announced that in a head-to-head trial testing CagriSema against Lilly’s Zepbound in obesity, Zepbound came out on top . Patients who were taking CagriSema lost 20.2% of their weight after 84 weeks, while those taking Lilly’s drug lost 23.6%. Then, Novo followed up with results about UBT251, its triple-G agonist going after the GLP-1, GIP and glucagon receptors. In a Phase 2 study, the data looked slightly better than Lilly’s more advanced triple-G, retatrutide, in its own similar trial. (These drugs were not pitted head-to-head.) Novo’s study was conducted by its partner United Therapeutics in China and enrolled about 200 patients. Despite the positive results for Novo, UBT251 will likely reach the market after retatrutide. And in a third trial, looking at oral GLP-1 drugs, Lilly’s orforglipron again came out on top over Novo’s Rybelsus pill. These data came from a trial conducted by Lilly in type 2 diabetes patients that isn’t intended to support approval, but could encourage doctors to prescribe orforglipron off-label. Patients given 12 mg or 36 mg of orforglipron for a year had their blood sugar levels cut by 1.71% and 1.91%, respectively. Those given Novo’s drug at 7 mg and 14 mg doses saw reductions in blood sugar of 1.23% and 1.47%, respectively. So what does this all mean? Senior biopharma journalist Elizabeth Cairns attempted to answer that question , and how Novo Nordisk and new CEO Maziar Mike Doustdar are navigating a “strategic conundrum.” Despite reaching heights that began to reshape Denmark’s economy in 2023, Novo’s stock price is now approaching a five-year low. Read more here. Endpoints founding editor John Carroll was surprised to see OrbiMed jump to number one on our most recent annual list of top venture investors in the life sciences sector. OrbiMed, which finished fourth in 2024, more than doubled the number of rounds it participated in last year, and total funding in those rounds rose from $4.5 billion in 2024 to $5.9 billion in 2025. RA Capital, which was in the top slot for 2024 and 2023, pulled back in 2025, taking second place. It participated in 37 rounds and invested $4.2 billion, down from 49 deals and $5.6 billion the year prior. There were other notable changes, including ARCH’s slide out of the top 10. The company landed at 11th with 26 deals in 2025, down from 33 the year before. The list highlights the growing role of big rounds in biotech. There were 103 venture rounds over $100 million in biopharma in 2025, compared to 93 in 2024 and 69 in 2023. That boost came as M&A sped up last year and the industry geared up for another round of IPOs. Click here to see John’s full breakdown of the top 100. In a surprising move, Sarepta CEO Doug Ingram said he would step down from his position at the end of the year, unless a replacement is found before then. Ingram said he is retiring for family reasons, as two of his immediate family members were diagnosed with myotonic dystrophy type 1, a progressive genetic muscle disease. Ingram’s decision ends a brash tenure in which he brought several Duchenne muscular dystrophy products to market and later presided over a spiraling share price amid intense safety and regulatory questions. The announcement came as a shock during the company’s earnings call, with no official press release or mention in the company’s earnings report earlier that afternoon. He became a contentious figure in the rare disease field. Sarepta won three new drug approvals using limited and often murky data, generating billions in revenue. Last year, the company faced intense scrutiny over patient deaths on its gene therapies, and ultimately pulled its Duchenne gene therapy Elevidys for older boys. Read more from reporter Lei Lei Wu, as she takes a bird’s-eye view of Ingram’s tenure — and what’s next for Sarepta. The FDA has been using an outside investigator in a probe of workplace complaints against CBER Director Vinay Prasad, Endpoints’ Max Bayer and Zachary Brennan reported this week. The Wall Street Journal previously reported the existence of some workplace behavior complaints against Prasad. Max and Zach reported that among the complaints are that Prasad created a toxic workplace, verbally berated staff and retaliated against staff pushback. The details come as FDA leadership continues to publicly defend Prasad against criticism. Commissioner Marty Makary called Prasad “a genius” in a recent CNBC interview. A spokesperson for HHS said in a statement to Endpoints that “this story is part of a PR campaign against Dr. Prasad.” Read more here. For all its blockbuster hopes and high-profile status in the gene therapy field, Roctavian’s commercial saga has ended, senior biopharma correspondent Andrew Dunn writes . After a few months of seeking to divest Roctavian, BioMarin said this week it failed to find “a qualified buyer” for the gene therapy and will voluntarily withdraw it from the market. The commercial failure is a reminder of the gap between promising science and a viable drug. Roctavian was never able to find a foothold in the market for severe hemophilia A, a genetic blood-clotting disorder. The drug brought in $36 million in 2025 revenue, up from $26 million the year before — but far less than the company and Wall Street initially hoped. DON’T MISS

It’s possible to imagine a world in which Novo Nordisk remained a medium-to-large European pharma company, a little like Merck KGaA or Boehringer Ingelheim, ticking over for hundreds of years, quietly changing patients’ lives without being part of a once-in-a-generation breakthrough. But Novo’s scientists invented semaglutide, and that possibility vanished forever. Semaglutide, the molecule behind a suite of blockbusters including Ozempic and Wegovy, went on to drive Novo to dizzying heights — in 2023 it briefly became the most valuable company in Europe, and at one point its market cap exceeded the GDP of Denmark, its home country. Since mid-2024, however, things have gone badly wrong. Next-generation weight loss drugs have disappointed in the clinic and on the commercial side; Novo has lost out to compounders and been outplayed at nearly every turn by its US rival in the metabolic segment, Eli Lilly. It also lost a high-profile bidding war with Pfizer for the long-acting GLP-1 developer Metsera, which would have added new programs to its pipeline. The company tried to turn a corner last May, ousting its CEO , and it’s been about six months since Maziar Mike Doustdar took over . But if anything, the company’s woes have intensified since, and the stock $NVO is now back where it was in May 2021. It appears that its earlier decisions cast a long shadow, and it’s unclear how long it will be before Novo is able to break free. “It has gotten worse,” Jefferies managing director Michael Leuchten told Endpoints News . He is clear about the scale of the challenge facing Doustdar: “The company is clearly in a strategic conundrum at the moment, and they’ve put somebody into the seat who, I think, from a commercial perspective, is very capable, but the company needs a little bit more than that.” The most recent mishap came from the trial Novo started to prove its GLP-1/amylin combo drug CagriSema was as good as Lilly’s marketed obesity shot Zepbound: In fact, it proved that Zepbound was the better drug and, astonishingly, generated the best weight loss data for Zepbound yet seen. “I am a big fan of a head-to-head — put your money where your mouth is,” Leuchten said. But he took issue with Novo’s suggestion that part of the reason the trial failed was that the patients knew which drug they were getting. “You can’t stand there after the fact and blame the open-label design,” he said. “You designed it. You designed a noninferiority margin. You picked the patients. And then the trial doesn’t work.” Another issue, Leuchten said, is that the pricing of Novo’s drugs has come down “a lot quicker than people expected.” Novo’s management cited the most favored nation deal it cut with the Trump administration last year as part of the reason for the dismal 2026 sales guidance it released at the start of February. The company’s decision this week to halve the list prices of some of its big sellers from 2027 could exacerbate this. Poorly designed clinical trials and falling prices factor into investors’ loss of faith in Novo. But the bigger long-term question surrounds Novo’s terminal value given semaglutide’s expected US patent expiry in 2032. “There is a cliff, and that cliff is about six years away,” Leuchten said. Even with that threat looming, Novo remains highly reliant on its big cash cow, according to Andy Hsieh, a biotech analyst at William Blair. “Basically, they anchored towards semaglutide. They think it’s the best thing in the world, without really having longer-term thinking about the obesity evolution,” he said. Novo has previously opted out of other mechanisms that have proved successful for other companies, such as GLP-1/GIP agonism, which underpins Lilly’s Zepbound. In August 2024, Novo culled a Phase 1-stage once-monthly injected GLP-1/GIP agonist for “portfolio considerations,” and a year later, terminated another, given weekly, that was in mid-stage trials. Hsieh pointed out that Novo had also stopped developing a triple-G — a drug that hits the receptors for GLP-1, GIP and glucagon. As if to compensate, it in-licensed another from United Biotechnology last year. That drug just outperformed Lilly’s similar drug, retatrutide, in Phase 2, but Lilly’s is likely to reach market first. “[Novo] had it in their pipeline, and they have to go out externally, get this triple-G from a China company,” Hsieh said. “It gives you a sense of maybe the longer-term foresight and decision-making process that might not be the most optimal.” In fairness, most of these decisions were taken before Doustdar took the helm. But Hsieh said the company is “very much still wedded” to CagriSema (which contains semaglutide as one of its components), despite the drug underperforming repeatedly in trials. “With the updated corporate strategy we introduced last August, we have doubled down on obesity and diabetes and taken steps to drive market expansion,” a Novo spokesperson told Endpoints. The obvious immediate step Novo could take to improve its fortunes is to buy in some new pipeline assets. It has been doing deals, but some — last May’s tie-up with Septerna and this week’s pact with Vivtex are cases in point — have been for candidates at a very early stage. Many Novo watchers want to see the company buy or license later-stage assets, perhaps for diseases outside its core focus of diabetes and obesity. It acquired Akero Therapeutics in October, gaining a promising late-stage therapy for the fatty liver condition MASH, a move made under Doustdar’s tenure that reversed an earlier decision to walk away. Michael Nedelcovych, a research director at TD Cowen, believes new assets in the cardiovascular area could be “natural bedfellows” for Novo’s current lineup. As an example, he pointed to the asset purchase Novo signed with KBP Biosciences in 2023, through which it gained a drug for uncontrolled hypertension and advanced chronic kidney disease. This ended poorly for Novo, however, with the Danish company taking an $816 million write-down less than a year later after the drug’s late-stage failure in chronic kidney disease. Last year, Novo sought to reclaim some of that money through the courts , claiming fraud on KBP’s part. “In theory [the drug] was great, but didn’t work out,” Nedelcovych said. He still favors hypertension and cardiovascular disease more broadly, as sources of diversification for Novo’s pipeline, as the large patient populations for these conditions can mean big sales. “We have a broad and deep pipeline across obesity and diabetes and their associated comorbidities such as cardiovascular disease and the liver disease MASH, with multiple assets with first-in-class and/or best-in-class potential,” the Novo spokesperson said. “We also expect a significant increase in the number of new projects to enter clinical trials this year, and the bulk of these will be in diabetes or obesity.” Nedelcovych described Metsera, by contrast, as “not a particularly attractive target,” and at the time of Novo’s bid for the biotech, it was hard to see what advantages its monthly injected GLP-1 and amylin drugs could have brought. It is just possible that Novo dodged a bullet here: When Pfizer reported mid-stage data on the most advanced obesity candidate it got from Metsera, its shares fell as the weight loss was lower than with Zepbound on a cross-trial basis. Despite this, Novo’s CFO Karsten Munk Knudsen recently said the company was still considering buying a long-acting GLP-1. But it is not a case of simply snapping up a promising obesity biotech, particularly since many other potential buyers are looking too. “Big pharma has probably shopped these assets very extensively,” Hsieh said. “It’s kind of hard to find that magic bullet and then really reinvigorate investor excitement in a very short period of time.” If Novo is able to build a more varied pipeline via dealmaking, Hsieh thinks it will be through a series of different acquisitions rather than one big one. “We have increased our business development activities in recent years, and we will continue to invest in the right external opportunities going forward,” the spokesperson said. They added that Novo intended to be “disciplined, and only pursue deals that help us meet our strategic and financial objectives.” “They do need a vision,” Leuchten said. “It’s not about the next three months. This is about the next six-plus years. It’s not about whether you run another marketing campaign on something. It’s about portfolio construction.” There is a hint of hope on the horizon, at least for the share price. Nedelcovych suggested that the 2026 sales guidance is so conservative that Novo has a good chance of beating the target — and then its share price will finally tick upward.