At Dr. Louis Aronne’s weight loss center in New York City, the reactions to new medicines like Wegovy and Mounjaro can be extreme. “People describe it as ‘It’s like a miracle,’ like ‘This has transformed my life,’ ” said Aronne, Director of the Center for Weight Management and Metabolic Clinical Research at Weill Cornell Medicine. His clinic works with people who have a significant amount of weight to lose or multiple health problems connected to weight, he said, not those “who are 10 pounds overweight.” For people in the former categories, he said, “It’s like we’re running a miracle clinic.”
However, the medicines, in a class known as GLP-1 receptor agonists, are so popular among all sets of people seeking weight loss that demand has outpaced drugmakers’ capacity to manufacture them. And while makers Novo Nordisk and Eli Lilly are racing to expand supply, a looming US Food and Drug Administration (FDA) approval for Lilly’s type 2 diabetes medicine Mounjaro to treat obesity may put even more strain on the system. “Over the past three to four months, I’ve had patients tell me that they can’t get it,” Dr. Jody Dushay, a Clinical Endocrinologist at Beth Israel Deaconess Medical Center, said of Mounjaro. As she prescribes the drugs for both diabetes and weight loss, “I’m aware of our supply literally on a day-to-day basis.”
Neither Ozempic nor Mounjaro is approved for weight loss specifically; the FDA greenlit them for type 2 diabetes in 2017 and 2022, respectively. However, doctors commonly use them off-label for weight loss. Wegovy, which was approved in 2021 for obesity, contains the same key ingredient as Ozempic, called semaglutide, while Mounjaro uses a slightly different one, tirzepatide.
All three drugs have been on the FDA shortages list at various dosages. Novo Nordisk, which makes Ozempic and Wegovy, has limited the availability of lower starting doses of Wegovy as it prioritizes a continuous supply of the drug for people who already use it. The company’s CEO recently told CNN that it would take years to catch up to demand. Lilly and Novo Nordisk are investing billions of dollars to expand capacity.
Lilly is building two plants in North Carolina, spending $4 billion to try to double production of so-called incretin drugs including tirzepatide, which mimic metabolic hormones that affect insulin secretion and appetite, by the end of 2023. That is when it anticipates an FDA decision on Mounjaro for chronic weight management, after clinical trials showed that it helped participants lose more than 20 percent of their body weight over 72 weeks.
Production is already online at one of the two factories, in Research Triangle Park in Durham. The facility uses high-speed automation, driverless vehicles and robotic arms to build autoinjectors for Mounjaro around filled syringes. The plant is also gearing up to do product formulation, in which the active ingredient, tirzepatide, is mixed with other components to make the finished medicine and then poured into syringes. Lilly said it is running the plant around the clock, every day of the week, to try to meet demand. Still, synthesis of the starting ingredient, tirzepatide, takes months, said Edgardo Hernandez, the company’s President of Manufacturing Operations, because it involves a series of chemical reactions to link together amino acids into a peptide, as well as purification and quality control steps. “It’s a massive scale of what we’re trying to do,” he said. “We are aggressively moving to deploy capacity.”
Mounjaro is on the FDA’s shortages list in the 10-milligram dose, the third-highest available. Hernandez said that is because the way people are using the medicine is different from what Lilly had predicted. The starting dose is 2.5 milligrams, and every four (4) weeks, patients can increase the dosage until they have adequate control of their blood sugar, according to Mounjaro’s prescribing information. Doses go up to 15 milligrams. “We’ve been learning all along,” Hernandez said. “We’re using artificial intelligence and machine learning to be better at predicting how patients are titrating through doses.”
For weight loss, Aronne said, the results in Lilly’s trial were similar at the 10 milligram and 15 milligram doses. Aronne helped run the study and consults for multiple companies working on medicines for obesity. “You could imagine that people would stop at 10,” he said. “A lot of people will tell you that they want to ‘save some room in case I have to increase it later on.’ ”
The medicines come with side effects, most commonly gastrointestinal issues like nausea, vomiting, constipation and diarrhea, making higher doses potentially less appealing. They have also been linked to a potential risk for more severe effects, like stomach paralysis.
Insurance coverage for the medicines can also be a challenge, and without it, they cost more than $1,000 a month out of pocket. Both the insurance issues and the supply issues have led to hard choices for clinicians like Dushay, who said she grapples with prescribing decisions while knowing there are not enough of the medicines to go around. “Because of all these complexities, it’s just made every clinic session just become this layer of being really philosophical about things,” she said. “You’re thinking about everyone’s situation in a way where there’s just more subjectivity in terms of thinking about who needs these medications more.”
Finding the medicines may be more difficult in areas with more wealthy people capable of paying out of pocket, Aronne said; he noted that has been his experience with patients in Manhattan. “We see a lot of businessmen, lawyers, people like that,” he said. “They could potentially afford these things, and they go buy it, so there’s a lesser supply.”
And while Mounjaro is already used off-label for weight loss, FDA approval for that use could boost demand even more, if experiences with Ozempic and Wegovy are any indication. Prescription information from data provider IQVIA shows that more than 1.9 million people had prescriptions for Ozempic in July in the US, and an additional 428,000 had prescriptions for Wegovy. “With the shortage, some might think that we’re not producing any products, but we have one of the biggest products in the category that’s growing by very large, double-digit percentage points,” Novo Nordisk CEO Lars Fruergaard Jorgensen told CNN in August of 2023. “So we’re ramping up significantly, and we’ll be investing a lot in the future years to come.”
Those investments are expected to see returns many times over: Investment firm BMO Capital Markets estimates that obesity drugs will bring in $100 billion in annual revenue worldwide by 2035.
Until supply ramps up, though, doctors like Dushay find themselves working with patients to try to increase time between doses or lower the amount people take at once, when they run into shortages. She said she has even had patients struggle to find the medications for long enough that they regain some of the weight they had lost. Lilly said it’s working as fast as possible to address the shortage. “We’re doing everything we can to stand up supply,” Dan VonDielingen, Head of the company’s Research Triangle Park site, told CNN. “It’s truly a privilege to be able to make medicine that’s life-changing for our patients.”
REFERENCE: CNN; 06 OCT 2023; Meg Tirrell