Ozempic and similar drugs for Type 2 diabetes and weight loss are in such high demand that the drugmakers have had a hard time keeping up. So compounding pharmacies stepped in to fill the gap, making their own versions of the drugs for more than two years.
The compounded versions are especially popular as cheaper alternatives for people whose insurance doesn't cover them.
But now the brand name manufacturers are pushing the compounding pharmacies to stop.
Novo Nordisk and Eli Lilly are moving to end compounding of their medicines for good. They say they are no longer in shortage (a necessary condition for legal compounding in this case), and that they are too difficult to compound anyway. The compounding industry disagrees.
As the battle over who gets what share of the multi-billion dollar obesity drug market continues, some patients are left wondering how they're going to get their next injections — and from whom.
What's underlying the fight, says Robin Feldman, a law professor at the University of California, is "the inordinate amount of money that is changing hands for the new weight-loss drugs, their incredible efficacy, the runaway demand. It's all about the dollars."
"When someone tells you, 'it's not the money, it's the principles,' [it's the] the money," she says.
The shortage rule
To understand why compounding pharmacists can make copies of semaglutide (the key ingredient in Ozempic and Wegovy) and tirzepatide (the key ingredient in Mounjaro and Zepbound), you have to understand the shortage rule.
Compounding pharmacists are licensed to prepare custom drugs for people who need them. For example, they'll make a liquid version of a brand name pill for a patient who can't swallow pills.
Drugs they make aren't generics — rather they buy ingredients from Food and Drug Administration-registered suppliers and prepare finished versions for patients with prescriptions specifically for compounded medicines.
Under the law, compounders are not allowed to prepare "essentially a copy" of an existing FDA-approved drug, but there's an exception when that drug is in short supply.
Once a shortage ends, that changes. That's starting to happen with these drugs.
Currently two of the drugs— Zepbound for obesity and Mounjaro for Type 2 diabetes — can't legally be compounded, but the FDA said it will turn a blind eye to the practice for now while it evaluates whether it was right to end the shortage earlier this fall. So patients and compounders are stuck in confusing legal limbo.
"Everybody knows that… [the] injections are going to come off the shortage list eventually and patients need to be prepared for that," says Scott Brunner, the CEO of the Alliance for Pharmacy Compounding, the industry trade group. "Compounded copies of these FDA-approved drugs are not a long-term therapy for these patients."
End the shortages, end compounding
The battle over compounding has intensified in recent months, taking twists and turns.
Over the summer, Eli Lilly, declared that Zepbound and Mounjaro were "available," implying that they were not in short supply anymore. On October 2, the FDA formally removed them from its official drug shortage list.
That meant compounders would be acting illegally if they compounded tirzepatide, the main ingredient in Zepbound and Mounjaro.
According to FDA rules, small compounding pharmacies can't make copies of available brand name drugs more than four times a month. And bulk compounders, called outsourcing facilities, can't fill orders starting 60 days after a shortage ends.
Jennifer Burch owns a small compounding pharmacy and a regular retail pharmacy about 15 miles apart in Durham, N.C. The week that the tirzepatide shortages ended, she tried to order more Zepbound and Mounjaro, assuming her patients would make the switch from compounded to name-brand versions of the drugs.
Only she couldn't. At the time, she could only order one box per day. That meant she could only take care of 30 patients per month — and she had a lot more patients taking compounded tirzepatide than that.
In November she told NPR she can only order two boxes per day, still nowhere near enough.
Scott Welch, a compounding pharmacist in Arlington, Va., says he can't order as much of the Eli Lilly drugs as he needs either. Before the end of the shortage, he said he had "thousands" of patients on compounded products.
"There's limited allocations on everything," he said, checking it in real time while on a Zoom call with NPR. "But they're completely out of Zepbound, 15 milligram and 10 milligram, Mounjaro 10 milligram…There's no allocation, zero availability to order any of it."
Compounders strike back
On Oct. 7, the Outsourcing Facilities Association, a trade group of large-scale compounders, sued the FDA, questioning whether the removal of tirzepatide from the shortage list was appropriate.
While the FDA looks at a number of factors before deciding whether to take something off the list, including the drugmaker's ability to fulfill backorders, Lee Rosebush, who chairs the trade group, says the agency didn't do enough. No one from the agency asked his group or its members how many patients they were compounding the drugs for.
"You'd think that would be a basic question because how do you know what the true market is if you haven't even asked how big it is?" Rosebush says. As a result, he argues, it's hard to know if Eli Lilly can supply the drugs for all the patients using name brand drugs and the ones who had been using compounded versions and would need to switch.
Currently, no reliable estimates of the compounding market for these drugs exist.
A few days after the suit was filed, the agency said it would re-evaluate its decision, allowing compounders to continue preparing tirzepatide in the meantime.
Eli Lilly reiterated to NPR that the drugs have been "available since August."
"Our current manufacturing investment of over $20 billion in the past four years is the most significant in our history, and will allow us to continue increasing capacity to safely bring these medicines to people who need them," Eli Lilly spokesperson Courtney Kasinger wrote in an email.
She said the company has additionally filed three lawsuits against compounders for improper marketing practices and using an unsafe version of tirzepatide, and she pointed toward an FDA warning letter against an unlicensed compounding pharmacy in California that recently shut down after a bad inspection.
And now, Novo Nordisk has taken a step that could signal semaglutide, the key ingredient in Ozempic and Wegovy, could soon come off the FDA shortage list, too. As of Oct. 30, it says all doses of Ozempic and Wegovy are "available."
Too difficult to compound?
And drugmakers are trying other ways to end compounding of the blockbuster drugs.
Novo Nordisk last month filed a petition to add semaglutide, the key ingredient in Ozempic and Wegovy, to an FDA list of drugs deemed too difficult to compound safely. Eli Lilly took a similar action in August.
"Our nomination provides numerous examples of these risks, including unknown impurities, peptide-related impurities, incorrect strengths, and even instances where no semaglutide was present in the product at all," Novo Nordisk spokesperson Jamie Bennet wrote in an email to NPR. "The urgency of the situation necessitates immediate action."
But there's a problem. The FDA drug list they reference? It doesn't exist yet. A proposed federal rule outlining how such a list would work hasn't yet been finalized.
"The comment period for the proposed rule closed on June 18, 2024," an FDA spokesperson wrote in an email to NPR. "The agency is in the process of reviewing comments for consideration in issuing a final rule."
Brunner, who heads the compounding pharmacist trade group, finds Novo Nordisk's timing puzzling.
"Most interesting is the fact that it seemed to take … over two years to muster enough concern for patient safety that they think this molecule ought to be placed off limits," says Brunner, who heads the compounding pharmacist trade group. "Compounders have been preparing the drug for the past two, two and a half years under FDA guidance."
As for the FDA, it says it will respond directly to Novo Nordisk.
Caught in the middle
While the battle over diabetes and weight-loss drugs is unprecedented, the drug companies aren't exactly using a new playbook, says Feldman, the law professor at the University of California.
"It's just part of the game," she says.
Feldman says government agencies don't want to be bogged down by lawsuits and other processes that keep them from doing their regular jobs. For one thing, lawsuits are expensive and agencies can't afford it.
"So when companies file these types of actions, ... it will make the agency gun shy in future circumstances," she says. "So this sets up a dynamic in which companies on both sides, either compounders or pharmaceutical companies, can threaten to tie them up for a while.
If they're both doing it, heaven help the public."
As for Burch and Welch, the compounding pharmacists NPR spoke with in North Carolina and Virginia, both say they received cease and desist letters from Eli Lilly prior to the tirzepatide shortage officially ending.
As small businesses, neither of them has a lawyer on staff. One has opted to continue compounding in light of the FDA's pause on enforcement as it reevaluates the shortage. The other has opted to buy compounded tirzepatide from an outsourcing facility, another type of compounder, instead of continuing to compound on its own.
Some compounding pharmacies are no longer filling these prescriptions at all.
Welch says when his customers can't get either brand-name or compounded products from him, he fears they will turn to what he called black market websites, which might have counterfeit products that could be harmful. "That is my biggest fear."
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