Orphan drug development within the Pharmaceutical industry

Pharmaceutical companies develop, produce, and market drugs for use as medications. The average cost of developing a new drug is $1.3 billion; this cost varies according to the complexity of the drug and the disease and would typically be lower for smaller organisations such as biotechnology (biotech) companies. Therefore, due to the extremely high costs involved, industry usually only start working on a particular disease once it is well understood and there is evidence that it can be treated.

Drugs which have been developed to treat rare diseases are often termed orphan medicines. As a result of small patient populations limiting the incentive for research and restricting the income generated from the sale of new orphan drugs, it has historically been challenging for the pharmaceutical industry to develop orphan medicines. This has led to the introduction of regulatory incentives to encourage development of drugs to treat rare diseases, through Orphan Drug Designation schemes led by regulatory organisations such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

The regulatory schemes provide special status to drugs designed to treat rare diseases and the incentives can vary slightly between different countries. These incentives can include:

• Market exclusivity: This provides the pharmaceutical company time to market their drug without direct competition from other companies developing a competitor drug i.e. a similar drug to treat the same disease. The specific number of years of protection depends on the regulatory organisation; in the EU, market exclusivity is granted for 10 years (plus another two years if the drug is used to treat children) whereas in the US, market exclusivity is granted for seven years.
• Regulatory fee reductions: Companies developing orphan medicines pay reduced fees for clinical trial protocol assistance, inspections, and regulatory applications e.g. to the EMA and FDA.
• Clinical development assistance: Clinical trials can be expensive and challenging to run. Regulatory organisations can provide assistance, grants and subsidies to companies to help them conduct clinical trials.
• Regulatory incentives: Regulatory review of new drugs can be a long process, and patients often cannot get access to a drug before the process is finished. Fast-track programmes developed by regulatory organisations have been developed to help provide faster access to orphan medicines by allowing them to gain marketing authorisation (approval to market the medicine) more quickly.
• Grants: Funding for rare disease research is available from specific organisations such as the European Commission or the OrphanProduct Grant Program in the USA. These organisations typically have an annual budget to provide funding for specific clinical trials.

As a result of these incentives, development of orphan drugs by pharmaceutical companies has increased over the years. Rare disease drug development has turned into a huge market, with worldwide prescription sales of orphan drugs totalling $127 billion in 2019. Industry continues to develop new treatments for rare diseases, with the orphan drug market expected to double to $255 billion in 2026.

However, several challenges surrounding drug development for rare diseases still remain:

1. There is often a poor understanding of rare diseases, including the natural history or cause of the disease. There is therefore limited evidence for potential or appropriate treatments, making it even more difficult for pharmaceutical companies to initiate research and development (R&D).
2. As only a small number of patients are affected by each rare disease, it can be difficult to recruit enough patients to participate in a clinical trial to assess how safe and effective a drug is.
3. As the drug will be used by a small number of patients, it can be difficult to achieve enough sales to make up for the huge amount of money invested into R&D; this often results in a high price for the drug.
4. As a result of having small numbers of patients in clinical trials and drugs carrying a high price tag, getting the drug to be accepted for reimbursement by a health service can be challenging as it is more difficult to prove that the drug will be good value for money. Further information on the reimbursement of a drug can be found in the “Health technology assessment” course.

This guide will discuss how patient groups can collaborate with the pharmaceutical industry to help overcome these challenges and begin to address the unmet need that remains in the rare diseases space.

Industry and patient group interactions

There are several benefits and successful outcomes that can be achieved through collaboration between the pharmaceutical industry and patient groups. It is not uncommon for patients to have concerns about working with industry, however, it is important to recognise that although there are differences between pharmaceutical companies and patient organisations, both share a common goal: to improve health for patients.

The industry now sees patients as key stakeholders in their drug development processes, and some companies even provide training to help patient groups interact with industry. This section will explain how different interactions can provide benefits to both the pharmaceutical industry and the patient organisations.

Why Might Patient Groups Want to Work with Industry?

Working with pharmaceutical companies can be greatly beneficial to patient organisations and their patient communities:

• Improved treatments:
  • By being involved in the R&D of new treatments, patient organisations can ensure the proposed treatment will address patients’ needs by:
    • Explaining the impact of their disease and what it is like to live with.
    • Highlighting the areas of unmet need patients are facing which can help direct the focus of R&D.
    • Inputting into the design of trial endpoints (target outcomes) by informing what unmet needs a drug should address.
    • Contributing to clinical trial design and set-up so that it is patient-friendly, e.g. telephone appointments so that the trial is more convenient for patients.
    • Participating in a natural history study which follows a group of patients to see how their disease progresses over time without treatment.
  • Getting involved in R&D can also generate confidence and hope among patient communities that research will have a measurable impact on their condition in the future.
• Resources:
  • Industry can provide funding to charities, allowing them to continue their work and provide vital support to patients. As it is often difficult to obtain enough resources to support drug development for rare diseases, pharmaceutical companies can provide a valuable source of funding.
  • Industry can provide time and various skills, including scientific, business and technical support and expertise to a project.
• Knowledge sharing:
  • Contributing knowledge and experiences from the perspective of rare disease patients can often improve the quality and relevance of research initiatives and/or industry-led publications, and ensure this important information is shared with a much wider audience.

Why Might Industry Want to Work with Patient Groups?

Companies are becoming increasingly keen to engage with patient groups for a number of reasons:

• Successful drug development:
  • Increasingly patients are being recognised as the experts in rare conditions and with research being limited and natural histories often incomplete, effective patient group collaboration can deliver key insights to a drug development programme from its inception to the point it is first marketed. Patient involvement may include:
    • Introducing the pharmaceutical company to an already established patient community so that more patients can get involved in contributing to R&D or participating in trials.
    • Increasing the efficiency of trials, by assisting with patient recruitment and retention; this can help save time and money.
    • Supporting market access discussions so that the drug can be made accessible to patients more quickly.
    • Further examples of patient groups contributing to the drug development process are explained in the “Supporting Drug Development” section of this course.
  • Corporate social responsibility(CSR):
    • Companies try to engage their local communities and disease communities by providing grants and encouraging staff volunteering.
    • Most companies have clear CSR programmes around engaging local charities and specifically patient organisations.

Different types of interaction between patient groups and industry

There are several different ways in which companies and patient groups might interact:

• Collaborations: Companies and patient groups might collaborate to work together towards a mutual goal, such as improving the lives of patients with the specific rare disease.
• Pro Bono: A company may offer support and services to patient groups free of charge, to achieve certain social aims as a benefit for their company.
  • This is a great way to obtain the additional resources needed to help you achieve your goals.
  • As this support is unpaid, it may not always be top priority for the company. This can make it difficult to set and keep to deadlines; flexibility is key.
• Pay for Service: A company may hire patients as consultants to provide advice, or support with patient engagement/advocacy. Likewise, patient groups may choose to pay for industry services themselves.
• Funding: The company can offer funding for projects led by patient groups. Information on fundraising can be found in our “Fundraising” courses.