Repurposing of Prescription Medicines

Closed 30 Mar 2021

Opened 4 Feb 2021

Feedback updated 10 Mar 2022

We asked

We asked for your feedback to understand potential obstacles and/or incentives to repurposing of medicines that may influence a sponsor’s decision to extend an indication for an existing medicine – in particular for those indications that are: 

  • already approved overseas 

  • for a less common disease 

  • already accepted clinical practice albeit ‘off-label’ 

  • likely to be less commercially profitable. 

The public consultation proposed options and ideas that may reduce barriers or encourage sponsors to seek registration of new indications. The three key areas are reducing regulatory burden (fee reduction, simplified submissions, and exclusivity); supporting the development of repurposed drugs through improving access to information (off-label use, and consolidated international regulatory information); and actively pursuing new indications (e.g. using non-commercial entities). 

You said

We received 59 submissions in response to the consultation, including from research, government, health professional, consumer and industry organisations, as well as from individual consumers. There was broad support for repurposing of medicines but some issues and obstacles were raised. You said: 

  • Regulatory burden reduction: Respondents were supportive of the TGA providing fee relief for certain repurposing submissions and streamlining simultaneous submission for regulatory and reimbursement evaluation. 

  • Use of real world data: Most respondents welcomed the use of real world data. There were concerns over a lack of guidance documents and information about the type and quality of real world data that the TGA will accept as part of a submission. 

  • Intellectual property rights and limitations: In the event that a medicine has patent protection, the sponsor runs the risk of infringing on another company’s patent. When a medicine is off-patent, there is a lack of incentive for generic companies to apply for a generic extension of indications. 

  • Enabling exclusivity periods: Respondents raised issues over the feasibility of an exclusive period for the new indication of a repurposed medicine. An exclusive period could infringe on the PBS current price disclosure and pricing policies. 

  • Erosion of ‘comparator’ medicine subsidisations: Respondents raised that if a proposed medicine was benchmarked to an existing comparator medicine on the PBS, the price of proposed medicine may be driven down on PBS. 

  • Clinical equipoise: Respondents highlighted that when a medicine has been used off- label for a prolonged period of time, and there is sufficient observational evidence to suggest its effectiveness, it would be difficult to conduct clinical studies that meet TGA’s criteria for evidence of efficacy and safety. In addition, large randomised trials are not feasible or ethical for rare diseases. 

  • Allowing/encouraging a non-commercial entity acting as sponsor: Many respondents discussed the feasibility of non-commercial entities acting as sponsors.1 The main issue lies in which stakeholder is responsible for the financial liabilities and legal responsibilities for the repurposed medicine. 

  • Alignment to company strategy: Respondents raised the potential impact of repurposed medicines on the company’s business strategies and image, particularly if they supply multiple treatment options for an indication. 

  • Compelling a sponsor to register: The vast majority of industry respondents did not support compelling a sponsor to submit an application to add indications. It was clear this was seen as against the principles of a free market. Beyond the efforts involved in an application, it was suggested this would impose additional pharmacovigilance responsibilities on an unwilling sponsor and this could have significant medicolegal, resourcing and financial consequences for the sponsor.  

  • Deeming an indication: Most industry respondents did not support the suggestion of TGA ‘deeming’ an indication without sponsor agreement. There was more support for TGA to do so with consent and agreement, particularly if the noted pharmacovigilance responsibilities could be limited or alleviated. 

Thank you to everyone who provided feedback and helped us understand some of the obstacles and issue you see around repurposing of medicines in Australia  

We did

We will use the feedback to shape regulatory reforms and policy options. It is likely that there will be further consultation as the Department considers the feedback and formulates options. Implementation of some options would require government approval (regulatory change) and/or parliamentary approval (legislative change). 

Published responses

View submitted responses where consent has been given to publish the response.

Overview

Repurposing is the process of identifying new uses (or ‘indications’) for medicines. In some cases, prescription medicines may have been used ‘off-label’ for many years to treat conditions that they do not have formal regulatory approval (i.e. are not registered) for. Whilst this may be accepted clinical practice, obtaining formal regulatory approval for the repurposed indication can lead to wider and safer use as it means that the evidence base for such clinical use has been independently reviewed and found sufficient, and that the benefits of such use outweigh the risks. Regulatory approval of the indication would also address the medico-legal concerns that can arise from off label use, increase patient and healthcare practitioner confidence and enable the possibility of reimbursement for the indication through listing on the Pharmaceutical Benefits Scheme (PBS).

Repurposing older medicines is generally considered by industry to be a lower risk and cost activity compared to the development of new medicines. In order to register a new indication on the Australian Register of Therapeutic Goods (ARTG) for an existing medicine, a sponsor is required to make an application to the Therapeutic Goods Administration (TGA) with scientific data to support the new indication. As preclinical development will have already been completed there is likely to be an established record of safety for the medicine which can be generalised where the dose and patient populations are similar for the new and existing indications.

Recently, repurposing older medicines has been a prominent area of research for potential COVID-19 treatments. Repurposing has also been recognised as a key topic in public submissions for the ongoing inquiry into approval processes for new drugs and novel medical technologies in Australia by the House of Representatives Standing Committee on Health, Aged Care and Sport.

In recent years, the TGA, often in cooperation with the relevant clinical colleges has promoted repurposing directly with sponsors, with mixed success. Some examples are listed below:

Tamoxifen

Tamoxifen has been in clinical use for the treatment of breast cancer since the 1970s and is registered and reimbursed for this indication in Australia. Tamoxifen was also approved by the United States Food and Drug Administration (US FDA) in 1998 for the reduction in breast cancer incidence in high risk women, but was not approved in Australia or reimbursed for this indication despite wide ‘off-label’ use for this purpose supported by recommendations in Australian and international guidelines.

To facilitate registration of the ‘off-label’ indication, the TGA worked with the innovator sponsor of tamoxifen to develop a literature based submission. This approach streamlined the application process with a focus on safety and efficacy without the requirement for quality or nonclinical information (as this was already established). Despite tamoxifen being off-patent at the time, none of the generic manufacturers took an interest in applying to extend indications because, as stated at the time, this was not part of their usual business model. 

Rifampicin

Rifampicin was as an important ‘off-label’ treatment option for Buruli ulcer, a skin/soft tissue infection due to a mycobacterium, of growing concern in coastal parts of Victoria.

Although the market for this indication is quite small, a regulatory application was received and was approved by the TGA in October 2020 (in combination with another antibiotic). Rifampicin was subsequently listed on the PBS.

Dacarbazine

At the request of clinical groups, the TGA investigated the potential for repurposing dacarbazine for early stage Hodgkin’s Lymphoma. Despite repeated approaches to sponsors, no submissions were received. The TGA cannot compel a sponsor to make a submission.

These examples demonstrate that while some successes have been had, barriers remain to the repurposing of medicines.

Consultation scope

Scope:

  • Incentives and barriers to repurposing of medicines currently or previously on the ARTG, including both genericised medicines and innovator medicines under legal protection (eg under patent or exclusivity).

Out of Scope:

  • Medicines not yet (or previously) registered in the ARTG for any indication including new and novel medicines that may be still in the clinical development phase.
  • Extensions of indications to closely related conditions – e.g. use of an oncology medicine for a related tumour type or for the same tumour type in a different organ. “Cascading” extension of indications has become a very common approach to oncology drug development e.g. for PD-1 and PDL-1 checkpoint inhibitor antibodies.

 

Why your views matter

This consultation seeks to understand potential obstacles and/or incentives to repurposing that may influence a sponsor’s decision to extend an indication for an existing medicine – in particular for those indications that are:

  • already approved overseas
  • for a less common disease
  • already accepted clinical practice albeit ‘off-label’
  • likely to be less commercially profitable.

Consultation outcomes may be used to shape regulatory and reimbursement reforms and policy options, as well as input into the review of the National Medicine Policy. It is likely that there will be further consultation as the Department considers feedback and formulates options. Implementation of some options would require government approval (regulatory change) and/or parliamentary approval (legislative change).

How to respond

Submit your views by clicking the link below – this will step you through questions seeking specific feedback.

Alternatively, the full consultation paper can be downloaded and you can upload a response document on the final page.

What happens next

Consultation outcomes may be used to shape regulatory and reimbursement reforms and policy options, as well as input into the review of the National Medicine Policy. It is likely that there will be further consultation as the Department considers feedback and formulates options. Implementation of some options would require government approval (regulatory change) and/or parliamentary approval (legislative change).

Audiences

  • Anyone from any background

Interests

  • Hospitals
  • Medicare
  • Legislation
  • Pharmaceutical benefits
  • Rural health services
  • Regulatory policy
  • Prescription drugs
  • Preventative health