Start-up to sell ‘unapproved’ replica Ozempic, upending market

The US Food and Drug Administration has warned that substitutes such as the one proposed by Eucalyptus have not been tested by regulators for safety. Australia’s Therapeutic Goods Administration shares those concerns, as does the Royal Australian College of General Practitioners. But Eucalyptus says research it commissioned shows its product is safe, has been tested, and patients will make fully informed decisions before administering it.

Patients who buy through Eucalyptus will not receive pens of regular semaglutide, which is the active ingredient in Ozempic. Instead, they will get syringes of semaglutide sodium, a similar but different compound that is salt-based, Eucalyptus confirmed.

A spokeswoman for the TGA, which regulates medicines in Australia, said it agreed with the concerns of its US equivalent, the FDA, which has warned that salt-based forms of semaglutide have not been shown to work or to be safe.

“In these circumstances, the TGA has not evaluated the quality, safety or efficacy of the product,” the spokeswoman said of compounded medicine.

Safety risk warning

Ozempic has been approved by the TGA as a diabetes treatment but not as a weight loss medication. Wegovy, another brand of the same medication made by the same company for weight loss, is unavailable in Australia.

Novo Nordisk has told doctors and pharmacists not to prescribe or sell replica versions of its medicine. “These unregistered, unlicensed products present a potential significant safety risk to patients,” a spokesman for the company said in a statement.

The spokesman also confirmed that Ozempic would be in “limited intermittent” supply all next year. Eucalyptus’ clinical director Matt Vickers said there would be scant Ozempic available in Australia within weeks.

“It’s as close to none as you can probably imagine,” Dr Vickers said. He said Eucalyptus was moving to the compounded version of semaglutide to ensure its patients, many of whom had lost weight through Ozempic, had continued care with a product he said was safe and effective.

Ozempic soared to popularity last year after versions of it were linked to dramatic weight loss by a series of celebrities, including Elon Musk and Kim Kardashian, spurring extreme global demand. It has since been in short supply in Australia.

The results of Eucalyptus-commissioned tests by the Monash University Quality of Medicine Initiative comparing six samples of the Ozempic replica with the genuine article found they were chemically “comparable”.

“The report finds no evidence of significant difference between three formulations submitted for analysis,” it concludes, in one quote released for publication by Eucalyptus.

When the semaglutide sodium is dissolved for delivery via a syringe it changes form, with the sodium ion separating off. Dr Vickers claimed the Eucalyptus-commissioned tests showed “the final product is semaglutide, identical to that of the commercial product.”

Eucalyptus has not published the report. It is also a fraction of the size of a full clinical trial, such as those that drug companies must perform with real patients before their drugs are approved.

But most compounded products created ad hoc are not independently tested, and the law relies on pharmacists’ skill and ethics to create good medications. They can include things as simple as a powdered medication dissolved in liquid, or a dose halved, or a medication reformulated to remove something a patient is allergic to.

The TGA spokeswoman said these products were “unapproved” by the regulator, but were allowed under an exemption for pharmacists to compound. The Pharmacy Board of Australia, which regulates the legal and tightly monitored practice of compounding, said it was aware of some individual concerns about compounded semaglutide.

“To date, however, the concerns have not related to the health, conduct or performance of an individual pharmacist which would bring the concern within the jurisdiction of the board,” a spokesman said.

Consent to be sought

University of Adelaide endocrinology professor Gary Wittert said the Eucalyptus study should not be kept secret from patients. “It should be made available to people because that’s what informed consent requires,” he said.

Eucalyptus’ Dr Vickers said the company’s doctors would obtain fully informed consent from all patients when it began telling them of the change this week, but would not say how that would happen.

Eucalyptus has recently rebranded to emphasise healthcare but has attracted controversy with disclosures by its chief executive about misleading investors and ads that spruik erectile dysfunction pills to men who are impotent because of cocaine use.

Eucalyptus did have the Monash test reviewed by Francesco Sanfilippo, an associate professor at the University of Western Australia and senior pharmacist at Royal Perth Hospital.

“It is my professional opinion that the compounded semaglutide preparations prepared by [the two pharmacies] will be safe and efficacious for human use, and that their safety, efficacy and physicochemical stability will be similar to that of Ozempic,” Dr Sanfilippo said. He said the semaglutide in Ozempic and the compound version was chemically identical.

In the United States, Novo Nordisk has sued a number of pharmacists making compound semaglutide, alleging that their products are up to a third impure or contain banned ingredients.

The FDA has also warned against salt-based Ozempic alternatives, advising pharmacists the alternatives may not comply with American law and noting reports of patients having negative reactions.

Dr Vickers declined to comment on the US experience, but said every batch of semaglutide supplied to Eucalyptus patients would be tested for safety.

The dean of pharmacy at the University of Sydney, Professor Andrew McLachlan, said salt forms of medicines behave differently to the standard form, which could change how it interacted with a patient. He said that given high standards for compounding, safety was not likely to be an issue.

“Actually, the main concern would be lack of efficacy and or uncertainty about the efficacy,” Professor McLachlan said.

“This is not a simple medicine to make,” he said, adding that the molecules were larger and more complex to make than medications such as aspirin.

“It’s not just the medicine itself. It’s all the testing that goes around it to make sure that we have a high-quality medicine, so I would also say if people are using extemporise compounding, this is a short-term stopgap.”

Dr Vickers said he did not have details on where Eucalyptus’ pharmacy partners were getting their raw materials, but “we have verified the quality and accuracy”. He said other pharmacies had been making versions of semaglutide for some time after doctors began prescribing the compound version around the country.

David Crisci, chief executive of one of the pharmacies working with Eucalyptus, Infinity Wellness Group, said it had robust measures to meet compliance standards and patient safety. The second pharmacy Eucalyptus has partnered with refused to be named.

It is the pharmacies that technically sell to Eucalyptus’ customers, although the telehealth platform handles the payment, manages the relationship with patients, and directs patients’ prescriptions to its partner chemists.

Access to Ozempic is an existential question for the start-up, which says it has only 20 per cent of its customers in weight loss while industry sources describe it as the largest Ozempic-seller in the country. Lack of access is a public health dilemma for the millions of Australians who are overweight or diabetic.

It also poses a big question for Eucalyptus’ backers, the largest of which is the venture capital fund Blackbird, which has invested millions in the company and declined to comment. Woolworths, another significant investor, was contacted for comment.

Royal Australian College of General Practitioners president Nicole Higgins said she was concerned about Eucalyptus’ plans because of the FDA’s warning that salt-based semaglutide had not been found to be safe or effective by a regulator.

“What are the quality controls? What are the guarantees? What are the potential impacts, side effects, complications to the person who’s taking the medication?” Dr Higgins asked.