Source: CNN
If there’s a diet, Janet McCaskill says, she’s done it.
“I’ve tried WeightWatchers. I’ve tried keto. I’ve gone to a nutritionist,” said the 58-year-old grandmother, who lives in Knightdale, North Carolina, outside Raleigh. Some of the eating plans worked, she said – until they didn’t.
At the end of 2022, weighing about 212 pounds and fearful about her health after losing her brother and both parents to heart disease, McCaskill started using the diabetes drug Mounjaro off-label for weight loss. It’s part of a class of drugs known as GLP-1 receptor agonists, which also includes Ozempic, Wegovy and Zepbound.
“It literally saved my life,” she said.
But it was expensive, and after switching to a lower-cost version made by a compounding pharmacy last year, McCaskill now is worried she’ll lose access to her medication because the US Food and Drug Administration determined that a shortage of the brand-name drug has ended – which means compounding of the medicine must stop.
A law allowing compounding pharmacies to step in to fill gaps when drugs are in short supply enabled thousands, or even millions, of people to access costly GLP-1 medicines at a lower price point – something some physicians worried could create safety issues because compounded drugs are not FDA-approved. But for people like McCaskill, it’s been a lifeline. And as drug manufacturers dramatically ramp up supply, their access is changing fast.
“I’m devastated, to say the least,” she said.
In a little more than a year, McCaskill said, she lost almost 100 pounds and has maintained her current weight of about 117 pounds since. Her blood pressure is lower, and her levels of A1C, a measure of blood sugar, and triglycerides have come down, she said. She’s dramatically changed the way she eats and started exercising more.
McCaskill’s four granddaughters, ages 6 through nearly 12, were her “number one reason” for starting the medicine, she said. “They do cheer, and I’m as active with them as I’ve ever been.”
An office manager for an auto restoration and repair business, McCaskill said her insurance never covered Mounjaro. The drug uses the active ingredient tirzepatide and was approved by the FDA in May 2022 for type 2 diabetes; although McCaskill said her blood sugar was elevated, she didn’t have diabetes, and many plans don’t cover GLP-1 drugs for the purpose of weight loss.
She paid out-of-pocket for it instead, using a coupon from manufacturer Eli Lilly that cut the cost in half, but it was still about $500 a month, she said.
When Lilly’s coupon program ended in the summer of 2023, McCaskill’s health-care provider suggested another option: compounded tirzepatide, a version of the drug that’s not FDA-approved but which was made available legally through a local pharmacy. It was less than $250 for a month’s supply. McCaskill switched and continued to see benefits, she said; she’s been on that version since, and her husband started on it, as well.
Now, though, she’s worried they’ll both have to stop.
No longer in shortage
Last week, the FDA updated its database of drugs in shortage to remove tirzepatide, which had sat on that list – along with related semaglutide-based drugs, Ozempic and Wegovy – since 2022 amid unprecedented demand.
The move means the compounding of tirzepatide, like McCaskill’s local pharmacy did, has to end. And although it’s a signal that branded versions of tirzepatide-based drugs – Mounjaro, for diabetes, and Zepbound, approved at the end of 2023 for weight loss – are more widely available, it threw people like McCaskill into a panic.
“I was working until almost 10 o’clock last night answering patients’ questions,” said Michele Kessler, a physician assistant at Durham Women’s Clinic in North Carolina and McCaskill’s provider. “I’ve got all these patients who are doing very well, and they are going to be abruptly stopped without any warning.”
Compounding of medicines that are “essentially copies of a commercially available drug” is allowed by the FDA during a shortage, the agency says, but when a shortage is resolved, it’s allowed only if it’s not done “regularly or in inordinate amounts.”
Compounding can often be done if patients need a tweak made to a medicine, perhaps because they have an allergy to one of the original version’s ingredients or need a liquid instead of a pill.
“It’s like, you walk into a bakery, and you want chocolate cupcakes with white icing, we make those; if you want vanilla cupcakes with blue icing, we can make that,” said Jennifer Burch, pharmacist and owner of Central Compounding Center in Durham, where Kessler sends her patients for compounded tirzepatide. “We can do that any way you want it.”
Her pharmacy even makes medication for pets and can tweak the flavor based on animals’ preferences: fish, chicken or, in one case, bubble gum.
“I’m like, how did you figure out the cat likes bubble gum?” Burch said.
But lately, her employees have been working around the clock compounding tirzepatide and semaglutide, she said. Over the past six weeks, Burch said, they’ve filled about 900 prescriptions for compounded tirzepatide and 500 for compounded semaglutide, using active ingredients they buy from chemical suppliers that she says validate their products through what’s known as compendial testing to confirm they meet quality standards.
For compounded tirzepatide, Burch’s pharmacy charges between $200 and $400 a month, based on the dose.
Without insurance, Mounjaro costs $1,069 per month, and Zepbound is $1,060, according to Lilly. The company also offers a savings card for Zepbound to offer it for about $650 a month for certain patients who have commercial insurance that doesn’t cover the drug.
In August, Lilly also introduced less-expensive versions of its lower doses of Zepbound that come in single-dose vials; patients must draw up the medicine and inject it using a needle and syringe. The regular forms of the drug come in autoinjector pens.
The vials are available for self-pay through a Lilly program called LillyDirect, which facilitates access to doctors and shipping of medicines to patients. They cost $399 for the lowest dose for a four-week supply or $549 for the next dose up – the one McCaskill is on.
“A lot of us are not going to be able to afford to keep paying that,” McCaskill said.
‘Price is not a rationale’
It’s not clear just how many people are using compounded tirzepatide and semaglutide, because prescriptions aren’t tracked through traditional channels, according to Evan Seigerman, an analyst with financial firm BMO Capital Markets who closely follows Lilly and Novo Nordisk, which makes semaglutide-based drugs Ozempic and Wegovy.
He said some estimates put prescriptions for compounded versions as high as 20% of all prescriptions for the drugs.
Scott Brunner, chief executive officer of the Alliance for Pharmacy Compounding, estimated that millions of people could be using compounded versions – and many may not be able to switch.
“Price is not a rationale for dispensing a compounded medication, but the fact is, a lot of patients were able to afford the compounded versions of tirzepatide, and they’re likely not going to be able to afford the FDA-approved drug,” Brunner said.
His organization asked the FDA for a buffer of at least 60 days before compounding must stop to “ensure continuity of patient care.” He said he heard from more than a dozen member pharmacies that branded tirzepatide products still weren’t available through their ordering systems despite the shortage ending.
The FDA acknowledged in its statement about the end of the tirzepatide shortage that “patients and prescribers may still see intermittent localized supply disruptions as the products move through the supply chain from the manufacturer and distributor to local pharmacies.”
In response to an inquiry about the request for a 60-day buffer, the FDA said it doesn’t discuss interactions between the agency and firms.
Although compounding has enabled access for people who may otherwise not have been able to find or afford the real medicines, the practice can come with risks since it’s not regulated by the FDA the way branded and generic pharmaceuticals are.
“Doctors will ask me all the time … ‘How do I know the compounded version my patients are getting is safe and effective?’ And I’m like, ‘You don’t,’” said Dr. Angela Fitch, chief medical officer of care provider Knownwell and past president of the Obesity Medicine Association. “This is the problem with it all along.”
The FDA has warned that it’s received reports of dosing errors with compounded semaglutide products, including some that resulted in hospitalization, and that some products sold by compounders used salt forms of semaglutide, which are “different active ingredients than are used in the approved drugs.” It’s also warned about counterfeit versions of drugs and medicines sold that are falsely labeled “for research purposes” or “not for human consumption,” which the agency said could be harmful.
And Lilly and Novo Nordisk have taken legal action against some med spas, weight loss clinics, pharmacies and others selling compounded products that they say pose “significant risks to patients.” This week Novo Nordisk published a study it conducted in the journal Pharmaceutical Research that it said found impurities and lower concentrations of active ingredients in some compounded versions of its drugs.
The end of compounding GLP-1s?
But the end of the shortages seems unlikely to spell the end of compounding the medicines completely. For now, semaglutide remains on the FDA’s shortages list in the lowest dose of Wegovy, the version approved for weight loss. Novo Nordisk says it continues to invest in increasing its manufacturing capacity but didn’t say when the shortage would be resolved completely.
Even when it is, companies that have built business models around compounding, like telehealth provider Hims & Hers, may find ways to keep providing compounded versions by offering different doses than what’s FDA-approved. The company told analysts on its quarterly earnings conference call in August that it saw a path “beyond the shortage dynamic” in part through offering “personalized GLP-1 doses, which augment the commercially available dosages for patients.”
McCaskill said she hoped Lilly might consider lowering the price of its medicines further to make them more accessible to people who’d been depending on compounded tirzepatide. And Fitch railed against the lack of coverage from insurance companies for obesity care.
Data from trials shows that most people who stop taking GLP-1 medicines regain a significant amount of weight they lost, and McCaskill doesn’t want to backtrack on the improvements she said she’s been seeing in her health.
“I’ve heard some people are trying to split their doses, but I’m scared to do that,” she said. “I just don’t want to mess with anything when it’s working 100% for me.”