The Therapeutic Goods Administration (TGA) has commenced a timely public consultation into the repurposing of prescription medicines, which seeks to better understand the incentives and potential hurdles influencing sponsors’ decision-making on whether to extend the approved indication for an existing medicine. Of particular interest to the TGA is the viability of repurposing medicines for rare diseases or less commercially profitable indications, or in circumstances where the new indication is already accepted clinical practice, albeit ‘off-label’ in Australia or elsewhere.
As part of its consultation paper the TGA has proposed far-reaching changes that have the potential to significantly reduce the regulatory burden on sponsors when applying for the inclusion of a new indication, improve information sharing and access to related international regulatory and reimbursement approvals, and implement open access to Australian medicine usage data.
Repurposing and ‘off label’ use
Repurposing, also referred to as second medical use, is the use of a known drug for a new therapeutic purpose. Repurposing is a promising avenue in drug discovery and has been an active area of growth in the last decade for a variety of drug classes, particularly chemotherapeutic agents.
Among the most visible recent examples of potential repurposing have been the investigation of known medicines such as chloroquine and hydroxychloroquine (both anti-malarials), remdesivir (an antiviral developed to treat Ebola) and tocilizumab (a monoclonal antibody developed to treat rheumatic conditions) and numerous other existing medicines as potential COVID-19 treatments.
Repurposing has the important benefit of decreasing the overall cost of bringing a new treatment to market and broadening access to it by Australian prescribers and patients, as the safety and pharmacokinetic profiles of the repurposed candidate have already been tested and established in connection with its original indication(s).
In recent years, the TGA has worked with innovator sponsors to enable them to make submissions based on peer-reviewed literature, rather than clinical data, for registration of new indications for existing medicines on the Australian Register of Therapeutic Goods (ARTG). This in turn has enabled reimbursement for the indication through listing on Australia’s Pharmaceutical Benefits Scheme (PBS).
In one such example, the TGA worked with the sponsor of Tamoxifen, a well-known breast cancer hormonal treatment in clinical use since the 1970s, to submit a literature-based application for a new indication (the prevention of breast cancer in high-risk women), which is an off-label use supported by recommendations in both Australian and international clinical care guidelines.
However, the TGA cannot compel sponsors to seek ARTG registration for a new indication that does not meet the sponsor’s business objectives, even where widespread and clinically-supported off-label use exists. Commercial imperatives are therefore one of the main barriers to less profitable second medical use indications becoming registered and subsidised.
Proposed approaches to facilitating and encouraging repurposing of medicines
The TGA has outlined three broad approaches to encouraging ARTG regulatory and PBS reimbursement applications for repurposed medicines, summarised below.
Proposal 1 – Reduce regulatory burden
- Develop and provide specific regulatory support and guidance for repurposing medicines, including clinical trial design and scientific advice.
- Assist with the development of literature reviews to simplify literature based submissions.
- Facilitate access to comparable overseas evaluation reports, where they exist.
- Improve the coordination of multi-jurisdictional submissions with other regulators.
- Provide fee relief (currently a TGA application and evaluation for an extension of indication is approximately $148,000), for submissions for medicines that have low commercial returns but high public health gains.
- Streamline simultaneous submissions for regulatory and reimbursement evaluation.
- Provide exclusivity periods for the first sponsor of new indications of repurposed off-patent medicines.
Proposal 2 – Enhanced information sharing and access
- Facilitate open access to Australian medicine usage data.
- Provide a simple mechanism to find related international regulatory and reimbursement approval assessment reports or decision summaries.
Proposal 3 – Actively pursue registration and review
- Seek public expressions of interest for sponsorship of new indications of a medicine, potentially limited to non-commercial organisations.
- Compelling sponsors to make an application for an additional indication.
- Pharmaceutical Benefits Advisory Committee (PBAC) to have the ability to approve the inclusion of an additional indication without the need for an application by the sponsor.
The issues raised by this consultation paper have important and far-reaching implications for both innovator and generic sponsors, and it will be of interest to see the outcome of this first round of pubic consultation, which concludes on 30 March 2021.