By Dennis Dionne
There’s a standardization problem relating to rare and orphan diseases. For example, in Europe, a rare disease or disorder is defined as a disease that affects less than one in 2,000 individuals. In the United States, a rare disease is defined as a disease that affects fewer than 200,000 people.
When we look at the development of new orphan drugs, we see that the process is hampered by nonportable (nonstandardized) methodologies that must be uniquely re-created for each clinical trial, compound, and indication. While there are clearly differences in individual drug candidates that must be accounted for, the underlying process could benefit from a methodology that incorporates aspects of systematic development.
Consider the model used in the technology sector. There, products such as email, USB ports, computer chargers, and headphone jacks are all developed based on standards, which enables cross-channel communications and connectivity. We believe a similar standardized approach to orphan drug development could result in more and better therapies being made available to patients.
Implications for Orphan Drugs
Despite recent initiatives aimed at improving the speed at which new medicines for rare diseases are developed, there are fewer than 400 approved therapies for the more than 6,000-8,000 rare diseases recognized by the medical community, and fewer than 10 orphan genetic disease approvals in the U.S. since 2012. While this is notable progress from even 10 years ago, it is simply not good enough.
From drug discovery through development and commercialization, there are opportunities to standardize parts of the way in which treatments for rare diseases are made available. For example, the National Organization of Rare Disorders (NORD) suggests developing a process that would allow for Institutional Review Board (IRB) approval to be portable across different institutions. Further, NORD advocates developing IRBs of record instead of small, localized IRBs. According to organization, “These reforms would greatly streamline, simplify, and de-risk the IRB process.”
Barriers Start with Trial Design
Orphan therapies, by their very nature, require a different and more innovative clinical trial design than traditional therapies. Most notably, they need to accommodate a small disease population. Compounding that problem is the fact that many of the companies developing orphan therapies are “often small and inexperienced, with little practice in designing clinical trials in general, let alone trials for diseases that require an innovative design because of small and geographically dispersed patient population,” explains NORD.
In addition, there is often very limited information available regarding the burden of illness facing patients, their families, and caregivers. There’s also a lack of real-world evidence regarding rare-disease management.
While each rare disease must have its own study to assess the impact of symptoms on patients and caregivers, there is an opportunity to extract and share underlying methodologies. These methodologies include everything from concept elicitation interviews (open-ended questions to allow the patient or caregiver to respond from their own experience), to the way in which individual symptoms can have multi-organ impacts – of particular importance in understanding the whole-body impact of a single symptom.
Method Guidelines Alongside Clinical Trials
Another opportunity would be to systematically collect healthcare resource utilization and cost data relating to a particular disease. Current economic models fail to provide a robust method of assessing the health economic value of orphan drugs being developed to treat one symptom in a multi-symptom rare disease.
In the European Union, these issues are compounded further when assessments are made across multiple markets, all with different healthcare systems. After orphan drugs receive their approval, the manufacturers are required to conduct health economic assessments of their products by Health Technology Assessment (HTA) authorities. These evaluations often show that orphan drugs are not cost-effective due to the high cost. However, a great number of orphan drugs still receive reimbursement but without a standardized methodology, in either the U.S. or EU, orphan drug reimbursement decisions are based on equity arguments rather than systematic health economic assessments.
As a result, pricing decisions vary widely and with many individuals unable to access new treatments and their families left with insurance and reimbursement uncertainty alongside the impact and burdens associated with the rare disorder itself.
The Case for Standardization in Orphan Drugs
Standardizing certain discovery, development, and commercialization aspects of the rare disorder treatment process may help progress this significant medical and social issue. For instance, in our experience working to address breathing abnormality for patients with Rett syndrome, we know having portable methodologies to work with would have helped our efforts. Thus, we look forward to the development of standardized methodologies and novel health economic models to systematically collect healthcare resource utilization and cost data for rare diseases.
About the author: Dennis Dionne is VP of commercial affairs at Newron Pharmaceuticals, S.p.A., a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system.