Amid backlash, FDA changes course over shortage of Lilly weight-loss drugs

The U.S. Food and Drug Administration, after intense public pressure and a lawsuit, is reconsidering its declaration barely two weeks ago that a shortage of the appetite-suppressing drugs Mounjaro and Zepbound—both made by Indianapolis-based Eli Lilly and Co.—is over, a temporary about-face that will allow pharmacies to keep selling unbranded copies.

The extraordinary turn of events has caused confusion for patients who rely on the cheaper, off-brand versions and for the compounding pharmacies that have been allowed to make them as long as the official shortage continued.

The FDA’s sudden shift highlights challenges regulators and the pharmaceutical industry have faced amid unprecedented demand for the blockbuster weight-loss drugs.

“The credibility of the FDA in this case has suffered,” said Mariana Socal, a Johns Hopkins professor who specializes in drug shortages. She attributed the agency’s flip-flop to its surveillance system, which by law relies heavily on information from drugmakers and is geared toward identifying disruptions to supply rather than spikes in demand.

“That system is not necessarily in real time reflecting the correct balance of the market,” she said.

The recent upheaval began Oct. 2, when the FDA declared the Mounjaro and Zepbound shortage over after almost two years. It provided little detail other than saying that Eli Lilly had shown it could “meet the present and projected national demand” for the blockbuster drugs, while acknowledging that patients could still see periodic shortages due in part to the logistics of shipping the refrigerated medication.

Compounding pharmacies, which custom-make prescriptions, had to abruptly stop. That effectively shut off access to a source estimated to be used by millions of patients, triggering what pharmacists have described as a deluge of calls and text messages from panicked prescribers and patients. Some patients in online groups called it “tirzepageddon,” a word play on tirzepatide, the active ingredient in Mounjaro and Zepbound.

On Oct. 11, the FDA opted against fighting a federal lawsuit brought by compounding pharmacies, saying it would reevaluate whether the drug is available. It also said it would not take enforcement action—for now—against pharmacies making their own versions of weight-loss drugs based on Eli Lilly’s tirzepatide, according to a letter it sent to the Alliance for Pharmacy Compounding on Thursday.

“The abruptness of FDA’s resolution of the tirzepatide injection shortage left thousands and thousands of patients stranded with a prescription that could no longer be filled—and no speedy means of transitioning to the FDA-approved drug,” Scott Brunner, chief executive of the Alliance for Pharmacy Compounding, said in a statement Friday. He called the FDA’s clarification “wonderful news.”

The FDA hasn’t responded to requests for comment about why it shifted course so quickly, other than to say that it doesn’t comment on litigation. The agency has said compounded medications in general aren’t as safe as drugs that go through its review.

Eli Lilly, which has been waging an aggressive legal campaign against compounded medications, said in a statement that “nothing changes the fact that, as FDA has recognized, Mounjaro and Zepbound are available.” The drugmaker added that “it is important that patients not be exposed to the risks in taking untested, unapproved knockoffs.”

Lilly stands to lose millions of dollars from the competition. Mounjaro brought in $3.1 billion in sales in the second quarter alone and Zepbound brought in $1.2 billion.

Yet independent pharmacy experts cite reports from patients and prescribers that they have difficulty finding the drugs.

“It’s obvious that there’s not actually enough out there to meet all the patient demand,” said Michael Ganio, a senior director at the American Society of Health-System Pharmacists, which maintains its own list of drugs in shortage—including tirzepatide.

He added that the FDA’s reversal reflects the limits of its tools, such as having little historical data to project demand.

Compounding pharmacies are permitted—if they meet certain requirements—to make copies of drugs in short supply. Many have taken advantage of the shortages of Eli Lilly’s tirzepatide and Novo Nordisk’s semaglutide to make their own versions, spawning an entire industry built on selling the off-brand versions.

There is little public data about the volume of prescriptions for compounded weight-loss drugs. Some pharmacists estimate that up to 2 million Americans are using pharmacy-made tirzepatide, as well as semaglutide, the active ingredient in Novo Nordisk’s Ozempic and Wegovy.

Much of the appeal of compounded tirzepatide is that it’s far cheaper than Mounjaro and Zepbound, whose injectable pens have list prices above $1,000 a month.

“I have a seven-figure net worth and I cannot afford these drugs,” said Joan Masover, 72, a retired financial adviser in Iowa who has a prescription for compounded tirzepatide. “I think Eli Lilly deserves my money. They just don’t deserve that much,” she said, pointing to research that has found weight-loss drugs could be profitably made for a fraction of their list price.

Masover has insurance through Medicare, which doesn’t cover weight-loss drugs. She knew from the get-go that she could lose access to compounded tirzepatide as soon as the shortage was over. Now, she said, she is rationing her supply, which costs about $350 a month.

The lawsuit by the Outsourcing Facilities Association, which represents large-scale compounders, argued that “if ever an agency action were arbitrary, capricious, and contrary to law, this is it.”

The lawsuit contended that the agency failed to consider how many patients rely on compounded versions.

A week later, the plaintiffs and the FDA reached what amounts to a settlement, with the agency asking a federal judge in the Northern District of Texas to give it “the opportunity to reevaluate the decision at issue,” saying further litigation “may become moot in light of subsequent administrative proceedings.”

“The agency simply updated its website and put out a couple of bullet points without really explaining the rationale or the evidence,” said Andrew Grossman, a lawyer representing the plaintiffs. The FDA’s motion “speaks to the agency’s recognition that our case did raise serious claims about the agency’s actions,” he said.