Novo Nordisk's weight management drug semaglutide (Wegovy) has been in prolonged short supply due to "unprecedented demand," prompting increased -- and questionable -- interest in compounded formulations of the drug, physicians said.
Endocrinologists and obesity medicine specialists have been sounding the alarm about what they say amounts to bootleg semaglutide, concerned about safety and quality as compounders offer lower prices and easier access. Physicians say they're increasingly fielding more questions about compounded semaglutide, even as questions linger about how compounders can get around patent protections that are still in place.
"I can tell you, the consensus amongst legitimate practicing obesity endocrinology specialists is to avoid this, because it's just too much unknown," said Karl Nadolsky, DO, an endocrinologist at Spectrum Health in Grand Rapids, Michigan.
A simple internet search reveals what endocrinologists are facing. In a blog post, the Compounding Pharmacy of America states that it "has combined high-quality semaglutide with L-carnitine, a fat-mobilizing amino acid. This creates a powerful symbiosis of weight loss mechanisms that help you shed pounds at a consistent rate ... Simply visit your doctor to discuss your weight loss needs and determine if semaglutide is right for you."
An aesthetic medical center in Ohio called Cru Clinic also promotes compounded semaglutide on its site, featuring pictures of smiling patients on scales and in workout gear. It states that as an alternative to more expensive semaglutide, "We have access to semaglutide from a compounding pharmacy for on-going use" for $300 a month.
Compounded semaglutide is described as "generic semaglutide" on other sites, and is sometimes mixed with vitamin B12. Many other websites make similar pitches.
But physicians remain skeptical about compounded formulations of the drug.
Ricardo Correa, MD, EdD, endocrinology fellowship director at the University of Arizona College of Medicine in Phoenix, said compounders "are probably using the same active pharmacological part [semaglutide], but when you combine things and you add different excipients, the effectiveness -- if you don't measure that in a randomized controlled trial -- will not be the same."
Fatima Cody Stanford, MD, MPH, an obesity specialist at Massachusetts General Hospital in Boston, said, "My assumption would be that they're making an agent that's close," but that "I can't chance anything with my patients. I need to see the data to support the use."
Physicians' concerns about these products also may stem from memories of a 2012 outbreak of fungal meningitis tied to methylprednisolone acetate injections made by a compounding pharmacy that killed 64 patients in the U.S. and sickened nearly 800.
Subject to less stringent regulations, some said compounding pharmacies had become "de facto" small drug manufacturers, so Congress subsequently passed reforms around compounding.
Still, compounding pharmacy groups say they're within their rights to use semaglutide in products -- hypothetically speaking.
Industry trade group Alliance for Pharmacy Compounding (APC) wrote in an email to MedPage Today that semaglutide likely meets the criteria needed to be eligible for use in compounded products because it is not considered a "biologic," which can't be used in compounded drugs, and it's a component of an FDA-approved product.
But APC stopped short of acknowledging that compounding pharmacies are actually using the same substance, protected by Novo Nordisk patents, in compound substances.
"We didn't say that semaglutide powder was available to compound with, or that pharmacies should compound semaglutide, just that it IS a peptide that DOES meet the criteria," the email stated.
A spokesperson for FDA's Center for Drug Evaluation and Research (CDER) didn't rule out the possibility, either, noting that under federal law a drug used in compounding is exempt from normal FDA approval if it's "made using a bulk drug substance (active ingredient) that is a component of an FDA-approved human drug product, provided all other conditions ... are met," the spokesperson wrote. "Semaglutide is the active ingredient in an FDA-approved drug product."
APC also argued that compounders are stepping in to fill a gap in the Wegovy supply.
"The fact is, Wegovy has been on and off of manufacturer backorder, and is currently on the FDA Drug Shortage list – a distinction that means 503a compounding pharmacies MAY be able to compound it," the email stated.
The organization encouraged compounding pharmacies to seek legal counsel, however.
The FDA, too, wrote that although the law restricts compounding drugs that are "essentially a copy" of commercially available drug products, "we do not consider a drug to be commercially available when it appears on FDA's drug shortage list. Currently, we note that semaglutide (WEGOVY) injection is on the FDA Drug Shortages list."
Despite the potential loophole, Novo Nordisk -- which owns multiple patents protecting its semaglutide medicines, including diabetes drug Ozempic -- said in an email to MedPage Today that entities selling products containing semaglutide "may be infringing Novo Nordisk's intellectual property rights and/or violating applicable laws. Novo Nordisk will take such actions as it deems necessary and appropriate to protect its intellectual property rights."
Physicians also found it perplexing that compounding pharmacies would be able obtain the patented substance.
"Nobody knows how they're getting it," said Nadolsky of compounding pharmacies. "Who's making it? Novo's not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?"
Jacob Sherkow, JD, a professor of law and medicine at the Illinois College of Medicine, told MedPage Today that most active pharmaceutical ingredients a compounding pharmacy would use aren't actually synthesized at the compounding pharmacy.
Substances are bought from outside the U.S. where chemical manufacturing is cheaper, in countries like China and Ukraine, and then mixed with inactive ingredients and put in syringes at the pharmacy, Sherkow said.
Even so, semaglutide that's "made, used, sold, offered to be sold, or imported into the United States is possibly an act of infringement, if Novo were to sue them, if they had a U.S. patent covering any of that," Sherkow said. A lawsuit, however, would cost time, money, and would be complicated by patents that may cover a "pharmaceutical formulation" -- essentially a finished product -- not the active ingredient itself, he said.
Sherkow noted that compounding pharmacies play a crucial role for patients who need them -- but they aren't without some risks.
"The vast majority of restaurants, with some -- but minimal -- oversight, handle food that is not prepared properly, and could easily poison us," he said in an analogy. "And they do it every day, millions of times a day. A compounding pharmacy is operating in a similar space."
But endocrinologists and obesity specialists reiterated they wouldn't prescribe compounded semaglutide. To them, the stakes are higher than a bout of food poisoning.
Stanford said for all of her patients, she asks herself, "'Would I be comfortable?' And if I wouldn't, myself, be comfortable receiving it, then I don't need to prescribe it for someone else."
She added, "I understand we're frustrated because we can't get the GLP-1s [glucagon-like peptide-1 receptor agonists, the drug class semaglutide falls into], but just because it's desperate times doesn't mean we use desperate measures."
Correa added that a patient asked him last week about compounded semaglutide. But that without knowing exactly what's in it and how it works, it's simply too risky for the patient -- and for him as a physician.
"You're treating 100 patients and all of them have been doing fine with a compound medication you recommend. One develops a problem." Correa said, in a hypothetical. "That's it. That's the end of your career."
https://www.medpagetoday.com/special-reports/exclusives/99625
