Repurposing Medicines Toolkit - Guidance for navigating the process

• The TPP may vary and evolve throughout the development pathway and should be regularly reviewed to take account of new information or changing contexts. Characteristics to be defined include:
• • Target patient population
  • Efficacy/benefits to the target patient population
  • Formulation
  • Potential drug-drug interactions, co-morbidities and other safety risks in the target patient population
  • Route of administration
  • Are any specialist equipment or facilities needed to administer the therapy to patients?
  • Dosing
  • • What dosing is appropriate for the new indication? Does it require a different dosing strategy to the original indication?
    • Do you need to carry out a dose escalation study?
    • Note: Dosing rationale is often under-studied and needs very careful consideration early on to avoid selecting the wrong dose
• Is there a need to reformulate? (Visit IP considerations and partnership for further information)
• Most of these aspects need to be considered when drafting the wording for the new repurposed indication in the Summary of Product Characteristics (SmPC). The SmPC is the formal, licensed clinical particulars of the product, approved by MHRA and therefore instructs prescribers how to use licensed medicines. It is a pivotal document.
• Examples of target product profiles can be found on the websites of the World Health Organisation and the Drugs for Neglected Diseases Initiative.

• Research patient and service user needs and buy-in, to gauge appetite for the planned treatment and likely uptake by patients and their families or carers.
• • Speak to medical research charities and patient advocacy groups. The Association of Medical Research Charities (AMRC) may be able to help you find and contact the appropriate communities. The rare disease charity for patient groups, Beacon (formerly Findacure) may also be able to help.

• Involve a clinician(s) with experience in the relevant patient population right from the outset. The AMRC or disease-specific patient groups may be able to help with introductions.
• Who will be the sponsor of any future clinical trial? Early engagement could prevent delays further down the line.

• Is diagnosis established and timely for the indication you are aiming to treat?
• • Would existing diagnosis and care/treatment pathways support and allow for your planned intervention?
  • It is recognised that timely diagnosis is an issue for many rare diseases and that, in many cases, robust diagnostic pathways aren't yet developed. While this might not necessarily be a roadblock to developing a therapy it may influence therapeutic design

• Potential partnership opportunities may be determined by whether the therapeutic you wish to develop is covered by a current patent.
• To find out whether the therapeutic you wish to develop is covered by a patent (which may be relevant to its use in a particular indication, route of administration or formulation), you may search the European Patent Office website. However, ensure you consult with patent experts for full-scale searches to identify patents that may impact your freedom-to-operate. If you are part of a university your technology transfer office (TTO) should be able to help with this.
• If you have identified a product for repurposing, particularly if it is covered by a patent, first contact the originator company (the company that first developed the product and likely to be the patent owner) to discuss the possibility of partnering. Ways to make contact are covered in the section below.
• Progressing the project in partnership with the originator company is preferable as they may have data and know-how related to the product that could be relevant to the new use. They may also provide material for the trial and may lead the process of obtaining Marketing Authorisation licensing for the new indication.
• If the originator company are not interested (and they may not wish to disclose their reasons why due to commercial sensitivity) it may still be possible to progress, but you must be clear on the freedom to operate position, especially if the product is still on patent. If you are in a university your technology transfer office will be able to help with this. If you are a charity or patient organisation LifeArc may be able to assist you.
• If the originator company are not interested, you may wish to approach a generic manufacturer, or more than one – they may be able to advise on exclusivity and patent information. They may also be able to help with drug supply and possibly with Market Authorisation. The British Generics Manufacturers Association (BGMA) can help with introductions. Visit Resources - BGMA
• How to make contact:
• • Normally, the Medical Director or Business Development Team should be contacted in the first instance. Details can usually be found on the company's website.
  • If other routes fail, the company's Medical Information Service can be contacted. The contact details listed in the electronic medicines compendium may be useful
  • Some companies will have an established internal process for assessing such approaches and others will operate on a case by case basis, but you should gather as much relevant information as possible to make your case. It is also worth researching the company's current portfolio and stated areas of interest, to see whether the new indication aligns.
  • When contacting generics manufacturers, the Regulatory Affairs department would usually be the first port of call. Information can usually be found on companies' websites. The BGMA may be able to help, including assistance to broker a partnership with one of their members. Visit Resources - BGMA
  • When exploring potential relationships with companies it is important to remember that some future public or charity funding options may be limited if a longer-term commercial arrangement has already been entered into. This may be the right path to take for your project but it is worth seeking advice on contractual terms. If you are in a university your translational research office (if you have one) or technology transfer office may be able to help.
• The Marketing Authorisation holder for the primary indication(s) is often, but not always, the same as the patent holder.
• • You can search for Market Authorisation holders on the MHRA website. Visit Resources - MHRA for further information.
  • The Electronic Medicines Compendium (EMC) is a useful source of information.
  • Visit Beyond Clinical Trials - ''On-label'' or ''off-label'' prescribing

• How much, and what sort of, data is already in the public domain for this compound How much of this could be relevant to the planned new indication?
• • Where can these data be found?
  • • Publications
    • clinicaltrials.gov /ISRCTN for existing and previous trials
    • The originator company
    • Clinical networks, patient groups or charities
• Consider what data the regulators will need for clinical trial approvals and marketing authorisations and how any existing data could be utilised to support these activities, potentially minimising the need for generation of new data.
• Visit Non-clinical Discovery and Clinical Development for further information.

• The potential routes to patient access are complex and variable. Visit Beyond clinical trials for factors to consider.
• If you are partnered with the originator company, or a generic manufacturer, they should be able to navigate this stage. If you are not, then NHS England's Medicines Repurposing Programme may support this after Phase 2 trials.
• Consider consistency of supply: are there any potential challenges for ongoing supply of the drug for development work and future use by patients? You may wish to explore the state of the market for the drug through landscape analysis and discussion with manufacturers and/or generics companies. If it appears that there might be challenges to consistent supply, is there a route to overcome these?

How will each stage of development and evaluation be funded? It won't be feasible to have secured funding for the entire pathway before embarking on the development programme, but it is helpful to familiarise yourself with the funding landscape and which options may be open to you at different stages. Funders are contactable and can advise. Visit Funding for further information.