Rare But Not Forgotten: Opportunities in Rare Disease Drug Development  

This article was co-written by Samantha Zappia, Principal Consultant, SK Regulatory Solutions.

The World Orphan Drug Congress (WODC) brings together industry leaders working to advance orphan and rare disease drug development in one place for a unique three-day event. Many attendees arrive with the goal of meeting other players in the industry, learning from successes (and challenges), and holding productive discussions around improving access to these life-saving treatments. We both attended WODC for those reasons, particularly to have discussions around advancing rare drug development and to share our own regulatory strategy experiences. As an industry, we gain so much by sharing our stories and learning from each other. 

We held a fireside chat, ‘Rare but Not Forgotten: Challenges and Opportunities for Rare Disease Drugs,’ and talked through the challenges and implications in rare disease drug development. We shared our own stories so that others could walk away with practical suggestions because developing therapies for rare diseases certainly has its own unique set of development and regulatory hurdles. 

Here’s a brief look into our Q&A. 

What is a rare disease? 

In the United States, a rare disease is defined by the U.S. Food and Drug Administration (FDA) as less than 200,000 people living with the disease. Today, more and more sponsors are working on treatments for rare diseases with estimated prevalences of 30,000 or less.  

The FDA has acknowledged the challenges that sponsors face for rare diseases. In particular, the FDA released an external analysis in collaboration with academia, CROs, small and large pharma, and patient advocacy groups to break down the challenges. What are they? 

Some of the key challenges revolve around the overall awareness of the topics of appropriateness and availability of nonclinical models for a particular disease state, the discussion on the lack of precedent for novel biomarkers, and the challenges raised by having to develop those biomarkers or endpoints in the shortened development time frame of a rare disease program. 

In diseases where a model is not available or not applicable to the product modality, the key then becomes how to tell the potential nonclinical efficacy story through other routes. Developers must think through the benefits of a nonclinical model, ask the question, ‘What key aspects of our product’s story would the model demonstrate?’ and consider how to best demonstrate the mechanism of action through other means.  

Another major challenge for sponsors is strategy, communication, and planning. For example, you will need to consider when and how to apply for the Orphan Drug Designation and all the essential data you will need to support your application.  

What other challenges do sponsors face with clinical development? 

These challenges are usually driven by the small patient numbers, lack of awareness of the disease, and the potential heterogeneity of the disease. With such a small number of patients, the key to a successful clinical development plan is to ensure that you assess the best approach to clinical trial design, the use of controls, the accessible patient population, and the totality of the generated data from your trial(s). 

What are your recommendations for patient engagement?  

Consider partnering with patients and patient advocacy groups early on. When designing your clinical development plan and your regulatory strategy, you must review the patient-focused drug development guidances, and applicable FDA patient listening sessions, and prioritize getting involved early on with the patient community. In many instances with newly characterized diseases, the medical community at large is only just beginning to learn collectively about these diseases, and patients need the support of sponsors. 

What are your regulatory strategy pillars? 

There are a handful of essential items that should be heavily considered when outlining your regulatory strategy. They include: 

• Prevalence versus available patient population for clinical trials 
• Focus on the patients with a mindset of ‘building clinical trials with patients and not for them’ 
• Clearly communicate and partner with the FDA early on and as often as possible 

Is the FDA open to working with the industry on addressing some of these challenges and considerations? 

Numerous leaders within the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) have noted the FDA is willing to utilize ‘regulatory flexibility’ to help aid the development and approval of treatments for rare diseases, and we’ve seen this play out with some of the recent approvals.  

Additionally, the FDA has enacted the Accelerating Rare Disease Cures (ARC) program, which has resulted in a number of programs and pilot programs, including Support for Clinical Trials Advancing Rare Disease Therapeutics (START). 

Though there is more to be seen from the pilot programs, if sponsors have a clear regulatory strategy, partner with the FDA (and do not view them as a hurdle), and engage in thoughtful and frequent communication, they will have a better opportunity to expedite their rare disease drug development for patients in need.