Ozempic maker wants local substitutes banned

Novo Nordisk says complexity and shelf life make compounding inappropriate. But experts have put their weight behind the preparation.

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Novo Nordisk, maker of the blockbuster diabetes-turned-weight-loss drug Ozempic, has lobbied Australian regulators to prohibit compounded substitutes, citing concerns over safety.

But experts from the University of Western Australia say compounded semaglutide provided by Eucalyptus, one of the telehealth companies publicly prescribing compounded semaglutide to fill the gap left by worldwide shortages, contains “an active ingredient that is chemically identical to the active ingredient contained in Ozempic”.

In March last year, Novo Nordisk contacted the Pharmacy Board of Australia and AHPRA warning that while it accepted that pharmacists could compound medicines in certain circumstances, “it is not appropriate for pharmacies to offer compounded semaglutide”.

In its letter, which was released by AHPRA this week, Novo Nordisk called on the bodies to “consider a formal communication to all registered pharmacists to require the immediate cessation of [compounding semaglutide]”.

Novo Nordisk said it was unsure how the drug was being obtained and compounded, given it had the patent for the active ingredient of the drug and that semaglutide had faced shortages.

It also outlined the “complex” nature of the biological medicine being compounded, “which requires very advanced laboratory techniques in providing compounding services” and is not based on precedent.

Eucalyptus has since confirmed that its compounds are made by dissolving semaglutide salt.

“When dissolved in water, semaglutide sodium dissociates into semaglutide molecules and free sodium ions. This is basic chemistry,” UWA Associate Professor Frank Sanfilippo, a pharmacoepidemiologist and senior pharmacist at Royal Perth Hospital, told TMR.

Professor Sanfilippo was engaged by Eucalyptus to provide independent opinion on analysis performed at Monash and a second unnamed university on samples of compounded semaglutide from Eucalytpus’ two partner pharmacies, and Ozempic, he said.

A Monash University spokesperson previously told TMR that they were not provided with “an authentic reference material”.

But Professor Sanfilippo said that it was confirmed by amino acid sequencing that the active ingredient used by the partner pharmacies was identical to semaglutide.

“Based on my interpretation of the results of extensive analytical chemistry testing carried out by Australian and UK universities, it is my professional opinion that the compounded ‘semaglutide’ formulations prepared by [Eucalyptus’ two partner pharmacies] contain an active ingredient that is chemically identical to the active ingredient contained in Ozempic, and that they will be safe and efficacious for human use, and that their safety, efficacy and physicochemical stability will be similar to that of Ozempic,” said Professor Sanfilippo.

“Ozempic also contains free sodium ions by way of inactive ingredients it contains.”

Professor Sanfilippo also concluded that “the compounded semaglutide formulations satisfy the US FDA’s definition of ‘pharmaceutical equivalence’ compared with Ozempic”.

Associate Professor Philip Burcham, a pharmacologist and researcher in pharmacology and toxicology at UWA, reviewed the opinion of Professor Sanfilippo and said: “I evaluated the same analytical chemistry test data that was initially reviewed by Professor Sanfilippo and I concur with his opinion and conclusions.”

Eucalyptus has not confirmed where its compounding pharmacists obtain the semaglutide salt.

In its letter, Novo Nordisk also raised concerns over the drug’s shelf life.

It noted that Ozempic was a sterile injectable, meaning that, in alignment with PBA recommendations, it should be accompanied by a “beyond use date” of maximum 24 hours from the time of compounding.

Speaking to The Medical Republic, Eucalyptus’ clinical director Dr Matt Vickers said the company worked with compounding pharmacists to compound in accordance with the relevant standards to allow extended expiration dates of between 45 and 90 days.

The company “follows all relevant clinical and safety guidelines and expects the same of the pharmacies producing compounded semaglutide (including in relation to the facilities required to undertake complex compounding)”.

According to the current guidelines on compounding by the PBA, compounding pharmacists must assign beyond use dates in accordance with USP–NF 〈797〉 Pharmaceutical Compounding – Sterile Preparations.

While compounds prepared in less optimum conditions must have a maximum beyond use date of 24 hours, some more complex methods of compounding can extend storage timeframes for up to 90 days when stored appropriately.

David Crisci, chief executive of one of the pharmacies working with Eucalyptus, Infinity Wellness Group, previously affirmed that IWG would assure that all compounding would meet compliance standards for patient safety.

In recent communication with TMR, Novo Nordisk held firm on its position, saying that it “recommends compounded semaglutide products should NOT be prescribed or dispensed to patients”.

It added that Ozempic is indicated for the treatment of insufficiently controlled type 2 diabetes, and that the company “does not, and will not, support any type of non-indicated (off-label) use of a Novo Nordisk product at any time”.

Novo also flagged possible breaches of the AHPRA shared Code of Conduct through off-label promotion of a prescription-only drug, after it received queries about the legitimacy of medication supplied by some compounding pharmacies.

A spokesperson for the Department of Health and Aged Care told TMR that the TGA was investigating unlawful manufacture of prescription-only weight loss medications by “several entities”, and their advertisements, and will take enforcement action if necessary.