A Summary of CBI’s Rare Disease Clinical Development and Access Summit

Rho representatives joined regulators, industry scientists, and numerous patient-advocacy groups at CBI’s Rare Disease Clinical Development and Access Summit in Washington this past December. Attendees were able to share best practices in product development for rare disease programs in formal presentations and through informal networking. The following are 4 considerations for your development program that were highlighted during the conference.

1)  Seek early engagement for patient and caregiver perspectives and with key  payers.
Sponsors need patient and caregiver perspectives in order to ensure clinical studies are properly designed to provide evidence speaking to issues that truly matter to patients and their caregivers. These interactions should start as early on in the process as possible, even as early as initial animal proof-of-concept stage. Patient advocates advised companies to be open, transparent, and humble in approaching their communities for these insights; patients and caregivers want their perspectives heard and know that increasingly they have great influence in shaping product development for their conditions. Because of this increasing influence, some patient groups are not waiting for outreach from product developers, and have conducted or are planning formal Patient-Focused Drug Development or FDA listening sessions so that the community can proactively shape FDA’s understanding of key concerns and priorities for product development.

It’s also important to engage with key payers such as Centers for Medicare and Medicaid Services (CMS) no later than End of Phase 2 so that the pivotal studies can provide data that will support reimbursement. Often this means exploring persistence of effect in a longer study than might be minimally required by FDA. And, on that note, don’t forget the perspectives of payers outside the US, including via the Health Technology Assessment processes in EU member states.

2)  Regulatory authority investment in rare disease development programs means more opportunities for dialog between regulators and sponsors: prepare for and embrace the increased access.
It is useful to note that in all these discussions about the development program, sponsors should make the most of milestone meetings and other opportunities to gain consensus with FDA on your plans. In 2018, 58% of the approvals were for rare disease indications and FDA speakers shared freely about how important and exciting this time is for them, patients, and industry. Precisely because FDA and similar stakeholders are so invested in these programs, and because these programs often include novel or challenging development issues, an iterative process in arriving at agreements should be expected. This will particularly be the case for topics lacking clear precedent owing to the rare nature of the disease in question. Therefore, it is imperative to identify key development questions and discuss them transparently with FDA and in hopes of settling key program questions by End of Phase 2.

3)  Plan early for Chemistry Manufacturing Controls (CMC).
Once your lead is selected, it’s critical to provide sufficient resources and advanced planning to the CMC development program. All too often, especially for a program benefiting from enhanced support and guidance from FDA via Breakthrough Therapy or Regenerative Medicine Advanced Therapy designations, sponsors find themselves with near-complete clinical programs backed by incomplete CMC packages. Proper planning and support is the only way to ensure nimble scale-up as development proceeds and as the team begins to prepare for marketing. In that light, as much as possible, avoid tweaks to the investigational product to avoid having an even higher hill to climb for the CMC program. By the same token, if the product needs a specialized delivery device, work to settle the design and performance features of this as early as possible to allow the team to focus on other things like running efficient trials. Finally, the same plan-ahead advice likely applies to the nonclinical program. Interested in knowing more about how to plan for your CMC development program? In the near future, another blog post will address this topic, so be on the look-out.                                                                    

4)  Strategize for how to streamline your clinical trials while still supporting your claims.
In rare disease, recruitment and retention for clinical trials can be increasingly difficult due to the small population size. Creating a streamlined program strategy that will support your potential label will assist in a more efficient product development program. If the disease course, genotype, and phenotype are poorly understood, a natural history study is an absolute must to gain valuable information about the disease and potential endpoints that would be of value to your proposed claims. Remember that the first-in-human study may end up being the pivotal study, so it has to be well designed and as flawlessly executed as possible to deliver the best possible data. Perhaps this is easier said than done, but it’s a fundamental pillar of successful product development, particularly for rare diseases. Even if your first-in-human study does not become your pivotal, you should look into alternative study designs that can reduce your sample size and discuss with the agency the composition of the program to understand the expectations for that indication and claim.

Topical, targeted industry meetings like this are excellent opportunities to share ideas and best practices in a small setting with a wide range of highly experienced people, which is why Rho staff regularly attend and contribute to such meetings. No meeting can offer a comprehensive view of everything that can come up in your development program or risks and opportunities to consider, which is why having an expert partner can be invaluable to your program. Contact us at any point in your development program for a free expert consultation; you’ll be pleased with our team’s thoughtful and creative review.

Meagan Spychala, PhD, Assistant Vice President of Patient Engagement and Program Strategy at Rho, serves as Rho’s expert on patient-focused clinical research activities and incorporates the patient and caregiver voice and experience into the clinical development program.  She recognizes the uniqueness of each clinical trial, which is especially true within rare disease clinical research, and understands the importance of each patient in the development program.