Rare Disease: Sustained Progress in Development Regardless of the Pandemic

Sunday, February 28, 2021, was Rare Disease Day. With so much focus on COVID-19 throughout 2020, it’s important to recognize the continued work done in rare disease drug development by sponsors and FDA throughout 2020. In addition, a number of policies implemented in response to COVID-19 are expected to have a positive impact on rare disease drug development going forward. Yet, the lasting nature of these policies, post-pandemic, remains uncertain, creating an opportunity for rare disease drug sponsors to be proactive in engaging with regulatory authorities and the patient community to advocate the retention of these positive policy developments.

A quick review of the FDA’s Orphan Drug Designation Database for designations with a 2020 date finds that 476 Orphan Drug Designations (ODDs) were issued by FDA’s Office of Orphan Drug Product Development. This compares to 340 ODDs issued by FDA during 2019. This indicates that both product development and FDA resources remained focused on rare disease products, even during the exceptional strains 2020 brought to both groups. On August 28, 2020, FDA proceeded with the planned public meeting on “CDER Standard Core Sets Clinical Outcome Assessments and Endpoints Grant Program,” an important milestone in the COA Endpoints Pilot Grant Program where grantees were able to share their development plans for the COA standard core COAs sets and receive feedback from stakeholders. The COA Endpoints Pilot Grant Program launched late in 2019 and is part of FDA’s Patient Focused Drug Development efforts. Three grants were made to enable COA standard core set development in (1) migraine, (2) acute pain in infants and young children, and (3) physical function across a range of chronic conditions. The goal of the COA standard core sets is to establish a minimum list of impacts that matter most to patients, are likely to demonstrate change, and that should be assessed during a clinical trial.

Although not purposefully directed at rare disease clinical trials, FDA’s “Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency Guidance for Industry, Investigators and Institutional Review Boards” released on March 18, 2020, has in fact significantly benefited ongoing and newly initiated rare disease trials. FDA often updated the guidance throughout 2020, in April, May, July, September, and in December, each time addressing new questions and providing further clarity on trials for enrollment, remote visits, remote monitoring, and protocol modifications. Clinical trials for rare disease indications are particularly important to the rare disease patient community since there are approximately 7,000 identified rare diseases and a mere 10% have an FDA-approved treatment or therapy, meaning many patients can only access unapproved treatments through investigational studies. The policy changes made in response to the pandemic may pave the way in the future for decentralized, virtual clinical trials that are expected to significantly benefit rare disease studies where patient enrollment, engagement, and retention are exceptionally challenging. These policies allowed for integrating home health visits and telemedicine, direct-to-patient drug and supply delivery, and collection of data by portable or wearable devices. A November 12, 2020, Tuffs Center for the Study of Drug Development report found that “55% of active ongoing clinical trials have transitioned to remote and virtual execution models since early spring,” indicating that the transition to decentralized trial design is prevalent and may become the norm in coming years.

FDA implemented administrative simplifications, such as permitting applicants and sponsors to submit information to the Office of Orphan Drug Product Development through email submissions rather than the recently launched online portal for ODD requests. Congress also assisted in maintaining existing rare disease programs in 2020, authorizing an extension of the Rare Pediatric Disease Priority Review Voucher program in December 2020, that was, as we disused in an earlier post, at risk of expiring in the midst of the pandemic.

FDA’s rare disease focus in 2020 extended to minimizing the impact of COVID-19 circumstances for rare disease patients. For example, FDA quickly realized the increase in demand for hydroxychloroquine as a potential treatment for COVID-19 and established a priority review process for all generic hydroxychloroquine drug applications so that lupus patients could continue to access the drug for its FDA-approved use. FDA also worked with manufacturers of rare disease drugs as part of FDA’s supply chain management efforts in response to COVID-19.

Rare disease patients were uniquely impacted during the COVID-19 pandemic, with 74% of the NORD survey respondents reporting a medical appointment had been canceled due to the pandemic, and 29% of respondents reporting loss of a job, with 11% of those job losses also meaning a complete loss of health insurance. We are encouraged that sponsors continue drug development programs, as evidenced by the large number of ODDs in 2020, and that FDA continues to devote resources and attention to programs focused on rare disease drug development. We will monitor these areas in 2021 and remain hopeful that the clinical trial policies put into effect during the pandemic prove to be viable and accessible tools for future rare disease clinical trials.

On the patent exclusivity and investment fronts, orphan diseases have increasingly been on the forefront, with focus on drugs and partnering for these indications. This reflects a major shift and a breakaway from the traditional, narrower view of the value and importance of these programs. “Five or 10 years ago the dogma was that these indications would not necessarily warrant full investment, either for clinical development or patent exclusivity,” according to Morrison & Foerster’s partner Dr. Catherine Polizzi, recognized patent law leader with over 25 years in life sciences patent practice. “I thought this was a short-sided view, and that there was tremendous opportunity in rare diseases, not to mention the important attention needed for these patients. Those who previously ignored this have very much changed course.”