Weight loss drugs radically shifting regulatory environment

The extraordinary demand for off-label use of these drugs resulted in recent changes to the Therapeutic Goods Act 1989 (Cth) to ensure safety and efficacy for consumers.

The Australian Institute of Health and Welfare indicates that 66 per cent of adults in Australia have overweight/obesity, 74 per cent of First Nations adults and 38 per cent of First Nations children. Where there’s a market, there’s a supply and demand equation, and where limited stock and limited access exist, suppliers go looking for loopholes. The semaglutide drugs posed a significant problem for the Therapeutic Goods Administration (TGA), which approves these drugs specifically for use in treating type 2 diabetes mellitus (T2DM). Ozempic, particularly, is the best known brand name, which we’ll refer to for the sake of this article, but is representative of the other semaglutide medications.

Ethics and regulation

Issuing off-label prescriptions of medications is not illegal or uncommon, but it poses ethical and regulatory problems, especially where demand far outpaces supply. Ozempic posed a number of concerns for the TGA and the medical profession. The TGA lacks the powers to prevent off-label prescriptions. According to a statement from the TGA, “Off-label prescribing is a regular occurrence in the Australian healthcare system, used in particular for uncommon diseases and conditions, or in underrepresented patient groups. We do not have the power to regulate the clinical decisions of health professionals and are unable to prevent doctors from using their clinical judgement to prescribe medicines for other health conditions.”

Michael Cossetto is a partner at Bartier Perry. He says, “In short, compounded medicines are not required to be entered on the Australian Register or Therapeutic Goods (ARTG), so long as they are compounded by a pharmacist for a particular person. It is also possible for an ‘unapproved product’ to be supplied provided that specific conditions are met.”

This requires an application to the TGA that must:

• consider approved therapeutic goods for the patient’s medical condition

• consider risks of treatment

• obtain informed consent

• adhere to relevant standards of good medical practice

• check state and territory requirements

• check the unapproved therapeutic good is available and affordable for the patient.

In July 2020, Ozempic was made available on the PBS. It quickly established demand for its off-label use, in Australia and globally, leading Ozempic’s manufacturer Novo Nordisk to announce that off-label prescriptions of the drug had resulted in a worldwide shortage between April 2022 and late 2023. In September 2023, the TGA issued advice that semaglutide prescriptions should not be issued without a compelling clinical reason, and alternative medications should be considered for patients who were already taking the drug.

The TGA provided the rationale for limiting off-label prescriptions in regard to semaglutide medications. For a medicine to get listed on the PBS for a specific ‘indication’, or use, the pharmaceutical company must first apply to have the indication added to the medicine’s Product Information (PI).

Then, the company can apply for a PBS listing for that particular indication. The Australian Government depends upon the advice of the Pharmaceutical Benefits Advisory Committee (PBAC), an independent expert advisory body, to assess the application.

According to the TGA, the Government is legally obligated to:

• only list a medicine on the PBS where the PBAC recommends it

• obtain advice from the PBAC before a change can be made to an existing PBS listing, such as the medical conditions and patients that can be treated.

When assessing a medicine for a proposed PBS listing, the PBAC must consider the safety as well as the clinical and cost effectiveness of the medicine, and account for the alternative treatment methods.

Australia’s position

On 22 May last year, the Minister for Health and Ageing, Mark Butler, issued a press statement saying “the Australian Government is acting to protect Australians from the risks posed by injecting potentially unsafe and dangerous compounded replicas of weight loss products”. The overwhelming demand for semaglutide medications for weight loss and the subsequent shortage had resulted in two problems for the TGA and the Australian Government: a surge in private prescriptions and pharmacies compounding replicas of the popular commercial drugs. The result was compounded medications that fell through a legal loophole, not subject to the same regulations as medications listed on the government-approved PBS. The compounded medications are neither clinically evaluated, nor subject to safety, quality, or efficacy standards as TGA-approved medications.

According to Butler’s press release, new regulations that began on 1 October 2024 removed drugs like Ozempic and Mounjaro (GLP-1 RAs) from the pharmacy compounding exemption. The catalyst was the revelation that over 20,000 Australian patients had been injecting compounded weight loss products (“replicas”), with increased presentation of patients showing significant adverse events as a result.

Cossetto says, “The changes effectively removed GLP-1 receptor agonist (GLP-1 RA) products from the pharmacy compounding exemption – so that doctors were no longer able to prescribe GLP-1 RA compounded products for their patients and making it illegal to compound those specific drugs.”

Whether there is a basis for individuals to take legal action in the event of adverse reactions to compounded medicines, Cossetto says, “There could be potential legal action against the doctor who prescribed the compounded medicine, and possibly against the manufacturer. It depends on the reason for the adverse effect and who (if anyone) is at fault.

“Most importantly, the doctor must be sure it’s in the patient’s best interest.”

“Doctors still have a professional obligation to meet a standard of care, and they must have a reasonable expectation of clinical efficacy. They need to consider if their peers would consider the prescription of the compounded medicine as competent professional practice. Doctors still need to adhere to the Medical Board Code of Conduct. Most importantly, the doctor must be sure it’s in the patient’s best interest. Similarly for manufacturers – they have to adhere to GMP (Good Manufacturing Practice).”

Australia’s approach to restricting GLP-1 RA drugs like Ozempic aligns largely with the UK and EU in terms of regulatory framework, but things differ in the US, where direct-to-consumer advertising and marketing of prescription medications is permitted. Like the TGA in Australia, the FDA has also approved Wegovy for weight loss in addition to type 2 diabetes. In the US, Zepbound is approved for weight loss and obesity, and in Australia, Mounjaro is TGA-approved for the same conditions.

Preventing replicas

The FDA has also raised the alarm on compounded replicas of these drugs. In the US, the manufacturers have taken action to prevent pharmacists from doing so, with mixed results.

In 2023, a Florida judge ruled against Eli Lilly after the pharmaceutical company attempted to block compounded versions of its Zepbound drug (using the active ingredient tirzepatide).

US federal court judge Roy Altman wrote that Eli Lilly was attempting to get ahead of the Federal Food, Drug and Cosmetic Act. However, Novo Nordisk also alleged that compounded drugs contained lower concentrations of semaglutide than efficacious. Both companies have further claimed that some of the compounded versions of their products are known to have bacteria or high levels of impurities.

The affordability of these drugs is even more challenging for consumers in the US, especially for those without health insurance. Since July, President Donald Trump has pressured pharmaceutical manufacturers to provide medications directly to consumers at a lower price, and he has particularly called out the semaglutide medications. Consequently, Novo Nordisk made Ozempic (listed price of approximately $US1,000 per month) available online at its NovoCare Pharmacy, which ships directly to cash-paying buyers. It has also made Wegovy available at a cheaper price for cash-paying buyers.

Many Australians are in the same boat, unable to afford Ozempic, Mounjaro or the like. None are listed on the PBS at this point, despite GPs and the Health Minister seeking the advice from the PBAC on adding these drugs to the PBS.

According to the Royal Australian College of General Practice (RACGP), “Mounjaro is only available on private prescription with its recommended price beginning at $395 per month for the initiation dose, while the 2.4 mg dosage of Wegovy, which is the ‘recommended dose for the most effective results for weight management’, costs $460 per dose.”

In Australia, Ozempic for those who can access PBS subsidised prescriptions is $31.60 per month, or $134.27 per month for a private prescription (while new patients cannot access a private prescription, those who had already begun a course of Ozempic prior to the October 2024 regulatory changes can maintain their off-label prescription).

‘Disproportionately affected’

West Australian GP, Dr Mark Mellor, wrote a report to the Federal Government calling for patients to have better access to weight loss treatments. He told RACGP, “We are advocating for funded access to treatment, as a first step, for people with a body mass index over 40 with three weight-related health impairments or at least one severe weight-related health impairment.”

He added, “People in the lower socioeconomic groups are disproportionately affected but the least able to afford these treatments, but also you see higher rates of obesity and therefore weight-related health impairment in those groups. I believe there is an appetite there from the Department of Health to tackle this, they’re just not sure exactly how to approach it.”

Wegovy is presently awaiting a decision from the PBAC, which will meet in early November to consider the manufacturer’s submission for a PBS listing. If it succeeds, this may prove the precedent for further subsidies and access to GLP-1 RA drugs for a broader consumer base.