orphan drug

Patient advocacy as a strategy for orphan drug access

Governments have integrated incentives to accelerate and promote the approval of orphan drugs and the interest among pharmaceutical companies to develop these products is rising. However, expedited regulatory approval is by no means an assurance that orphan drugs will succeed in the marketplace.In the US, the Food and Drug Administration (FDA) defines rare diseases as conditions affecting less than 200,000 people.1 In Europe, the European Medicines Agency (EMA) defines these as conditions affecting five in 10,000 people.2 Due to their small target patient population, orphan drugs are met with many market access hurdles. First, the development costs are high and so the prices for orphan drugs per treatment are typically expensive. Some products can cost hundreds of thousands of dollars per year per patient, which has made payers sensitive to granting reimbursement for these products. Second, the small size of the patient population can make access to patient data and recruitment for clinical trials a challenge. Potentially, this leads to gaps in evidence quality with respect to safety and efficacy. Third, health technology assessment (HTA) agencies have a growing influence on the reimbursement decisions of payers. However, the assessment models these agencies use are very diverse. Some agencies focus on severity of disease, improvements in quality of life, budget impact, adverse events, mode of administration, or a combination of these. Failure to acquire HTA recommendations can lead to delays in access and reimbursement. It is up to orphan drug developers to put together value propositions that are compelling and targeted towards the priorities of these bodies.

Importantly, most HTA agencies prioritise the cost-effectiveness of products. In the case of rare diseases, however, an emphasis on cost-effectiveness may not be suitable. Orphan drugs aim to treat conditions that are debilitating, life-threatening and essentially have a high unmet need among patient populations that are so small in size that healthcare systems have traditionally, though unintentionally, failed to address their specific health requirements. Additionally, if orphan drug development is discontinued or the access to such products prevented due to lack of evidence for cost-effectiveness, it is possible for healthcare systems to be confronted in the long term with much higher overall healthcare costs due to their failure to treat patients with rare conditions.

Governments have put in place efforts to stimulate orphan drug research development precisely to address the need for social justice among minority patient groups.3 Therefore, for orphan drugs, patient advocacy must be a core consideration at all times. Companies need to take on a patient-centred approach to drug development and commercialisation and determine ways to continually expand the value story or orphan drugs.

Patient-centred development

Patient advocacy needs to be treated as a priority consideration early on. The development and commercial stages need to be patient-centric by design so that integrity with patients and patient foundations is maintained. During the creation of the value proposition, developers must aim to generate evidence that is characterised by the three elements of value: clinical, economic and patient value.4 Robust evidence continues to be a key ingredient to market access success and in orphan drugs each diagnosed patient can be a critical source for data to inform development choices, such as what endpoints to use.

Patient engagement is therefore fundamental to the orphan drug commercial model. To build awareness about the drug and gather the necessary data from patients, developers need to establish a deep level of interaction with patients and patient groups while remaining compliant with regulations. Indeed, it is not unlikely that orphan drug makers know almost every diagnosed patient for a rare disease by name.

Organisations that enter the orphan drug space range from small biotech firms to large pharma companies. Regardless of company size, building in-house capabilities for stakeholder engagement is necessary. For small companies, patient advocacy may need to be integrated into the role of everyone in the organisation to optimise each patient interaction. For large companies, interacting with patients at a personal level may be a challenge given the size of the company, and so a dedicated team that prioritises patient needs may be necessary. Teams in charge of patient engagement must be equipped with the right knowledge and skills to be able to effectively interact with patients and patient groups and to deepen relationships with them.

Valid Insight offers workshops that promote patient-centred development within pharma companies and we tailor our education programmes to the company’s specific needs. Specifically, we offer trainings on patient-reported outcome (PRO) development, clinical and economic modelling, value dossier creation, and how these can be achieved in a patient-oriented manner. PROs are important to determine unmet needs that go beyond the clinical aspect and to expand a pharma company’s understanding of the patient perspective. Health economic or cost modelling capabilities can support the product’s economic value during pricing and reimbursement negotiations with payers. Value dossiers are critical to communicate the comprehensive value that orphan drugs offer to all stakeholders.

Advocating for patient access to orphan drugs

Part of patient advocacy is ensuring that patients have access to the treatments they need. Due to a small sample size of patients during orphan drug clinical trials, evidentiary gaps around patient outcomes and cost analysis often exist at the time a drug is granted market authorisation. For the time being, companies will need to depend on the use of surrogate endpoints to evaluate the impacts of the drug. To safeguard against excessive spending, especially since many rare diseases require lifelong treatment, payers might set up measures to regulate access to orphan drugs.

Developers must have the capability to expand the existing body of evidence to be able to identify potential primary endpoints that have more relevance to the evaluation frameworks applied to the orphan drug. Payers will appreciate additional data and tools that help them to better assess the product’s value and arrive at a more sustainable pricing and reimbursement model.

Real-world evidence (RWE) building is one of the key services we offer to clients to help optimise the commercial success of their products. Real-world perspectives are significant to augment the value story of any drug or device as well as to identify potential demand for new therapeutic products. In orphan drugs, patient registries play a key role in enabling RWE generation. The target patient population in rare diseases is very small, resulting in these conditions being poorly understood. Registries are used to track patients for years and monitor their conditions and long-term responses to treatments, and are thus used to expand the research on rare conditions. Pharma companies either utilise patient registries created by patient groups or governments or build one from scratch. Either way, pharma companies must tap external capabilities for registry data analysis and RWE generation in order to continually evaluate the safety, efficacy, cost-effectiveness, and other benefits of a product.

Pharma companies can also take on a more novel approach to advocating for patient access to orphan drugs through the creation of managed entry agreements (MEAs). This type of scheme can simultaneously achieve earlier patient access to medicines while addressing the needs of payers for evidence on outcomes and costs, or by additional service provision. MEAs are still unfamiliar ground to many drug developers so we offer training opportunities to expand the knowledge and skills of market access teams in this area. To help secure access to orphan drugs, companies will require training on how to design and deploy MEAs and how to engage payers to support and partake in such agreements.5

Supporting patient advocacy groups

Another way to advocate for patients of rare diseases is to provide support and assistance to patient groups. Groups that are focused on rare conditions can be very dedicated and engaged. At times, they have on-going initiatives or clinical studies which partnerships can help expedite. For example, the Cystic Fibrosis Foundation (CFF) funded the development of a drug for cystic fibrosis. Later, they partnered with Vertex Pharmaceuticals and together they launched Kalydeco (ivacaftor) in 2012.6 Such groups have intimate relationships with individual patients and are often in a good position to identify patient needs that are still unknown.

Initiatives by patient advocacy groups are opportunities to cater to a rare disease market that comes with a pre-existing support system. Rare disease groups often maintain a community around patients and so involving these groups during the development process can address the recruitment and retention issues typical of orphan drug clinical trials. Moreover, patient advocacy groups can provide the market access push that orphan drugs seriously need. They can champion for the drug among regulators, policy makers and payers and build demand among patients and prescribers.

The small patient population size in orphan diseases can contribute to a substandard quality of evidence and a weak cost-effectiveness argument for orphan drugs. However, viewing the value of orphan drugs predominantly from an economic perspective is not a sustainable model to take. This will serve to create hurdles for patient access to treatment. To overcome market access challenges unique to orphan drugs, pharma companies need to advocate for patients. A strong focus on patient needs, along with an excellent ability to communicate a comprehensive view on value, will result in a broader understanding of value among all stakeholders and better reimbursement prospects for pharma.

To learn more about integrating patient advocacy into orphan drug development, contact us at



  1. FDA (2017). Developing Products for Rare Diseases & Conditions. Retrieved from
  2. EMA (2017). Medicines for rare diseases. Retrieved from
  3. Denis, A., Simoens, S., Fostier, C., Mergaert, L., & Cleemput, I. (2009). Policies for Rare Diseases and Orphan Drugs KCE reports 112C Brussels: Belgian Health Care Knowledge Centre.
  4. Valid Insight (2016). Taking a multipronged approach to commercialisation of assets. Retrieved from [Last accessed 02/07/17]
  5. De Wilde, R. and Jones-Phillips, D. (2017) Confidential contracting – the road to flexible pricing. Valid News Market Access Insights, Valid Insight Newsletter, Vol 01, Issue 01. Retrieved from:
  6. Welch, A. (2015). Venture Philanthropy: Is It Really Promoting Patient Centric Drug Development? Retrieved from
  • 0
  • 0
  • 0

Valid Insight is an award-winning pharmaceutical global market access consultancy. With a team that includes some of the world’s leading market access and pricing experts, clients across the globe turn to us for innovative pricing, market access and value communication strategies through the full product development cycle. Proud winners of the Queen’s Award for Enterprise: International Trade, we aim to offer world-class solutions that continue to drive growth for our global clients.

Leave a Reply

Your email address will not be published. Required fields are marked *