Celebrating 40 Years of Rare Disease Progress: WODC Highlights

The World Orphan Drug Congress (WODC) USA recently convened in Washington, DC for two days of thought-provoking discussion on research progress, regulatory initiatives and legislation influencing research innovation, rare disease drug development, and access to medicine.

This year’s event was especially momentous, taking place on the heels of several important regulatory activities, coinciding with the 40^th anniversary of the historic Orphan Drug Act (ODA), and the founding of National Organization of Rare Disorders (NORD) in the US. Prior to the ODA, only 38 therapies were approved for rare conditions. 40 years on, we are celebrating the approval of over 700 new drugs and biologics for rare diseases, and development of countless more in what was previously a commercially non-viable pathway.

The Orphan Drug Act was foundational to the creation of accelerated regulatory pathways, development of cutting-edge therapies and for including the patient voice into drug development in a meaningful way. Since its inception in 2010, WODC continues to provide an ideal forum to celebrate advancements in this explosive area of science and advocate for continued improvements in critical areas of:

• Shortening the diagnostic odyssey for the over 400 million patients who suffer from rare diseases
• Stakeholder collaboration to enable ground-breaking regulatory pathways
• Advancing health equity in an era with rising economic burdens on families and society
• Harnessing creativity for making the impossible possible

I had the privilege of moderating a panel of industry luminaries on the topic of expediting gene therapy drug development, building on the momentum of successful streamlining and regulatory collaboration seen in COVID-19 drug development. The distinguished roster included Peter Marks, Director, Center for Biologics Evaluation and Research (CBER), FDA; Kinnari Patel, President & Chief Operating Officer, Rocket Pharma; Adora Ndu, Chief Regulatory and interim Legal Officer, BridgeBio; Michael Lynch, Head of Regulatory Affairs CMC, Regulatory Operations and Regulatory Operational Excellence, Alexion, AstraZeneca Rare Disease and Annie Kennedy, Chief of Policy and Advocacy, EveryLife Foundation for Rare Diseases.

On the topic of successful initiatives, collaboration and platform approaches were common themes:

• Collaboration between researchers, sponsors, patient advocacy and regulatory agencies are generating impressive results, most notably the flexible regulatory approaches enabling next-generation and potentially curative therapies. The people who have dedicated their careers to rare disease advocacy are finally beginning to see the fruits of their labor.
• FDA’s CBER is leading the charge to streamline gene therapy manufacturing for platform technologies, proposing a pragmatic approach to CMC data requirements with every small change to the platform product. For example, sponsors will only be required to submit platform CMC data once, with smaller data package requirements where indication specific changes are made, lowering the CMC burden for gene therapy developers.
• Modelled on the collaborative approach taken through the COVID-19 pandemic, FDA will be implementing a communication pilot for rare gene therapy technologies at the end of 2023. Operation Warp Speed for rare disease will allow sponsors to request advice and provide preliminary data between the usual pre-IND/post-IND interactions, expediting rare drug development for patients with the highest unmet need.

Other key discussion highlights among this panel included:

• Current funding in rare healthcare still does not meet the public need, as a disproportionate percentage of healthcare costs are shouldered by rare families. Incentives are vitally important to the future of rare disease, beyond the drug development bubble.
• The research and patient community needs pragmatic, science-driven flexibility and better pathways. On the discussion of the need for pragmatic approaches to “best available scientific data”, natural history studies have transitioned from informing clinical trial design to informing regulatory decisions. Panelists cited the recent approval of Skyclarys for the treatment of Friedreich’s Ataxia (FA) as an example of the power of the patient community to influence regulatory recognition of the lived experience of the FA community and use existing patient registry data as an effective control.
• Clarifications in the definition of compelling evidence for regulators alongside payers are desperately needed. As most gene therapy products approved to date are unique, drug developers and the rare patient community feel the goalposts are constantly changing. In addition, the separate and often inconsistent adjudication processes for regulatory and reimbursement negatively impacts the speed in which vital therapies reach patients.
• While there are early signs of progress for solving persistent manufacturing issues, Peter Marks emphasized the need to make good use of vectors to get through hundreds of diseases and ensure people will be dosed safely.

Other stand out topics among presentations, panel discussions and roundtables included:

• How to meet the diverse needs of smaller patient segments. Nowhere was this more impressive and ambitious than in the efforts of nLorem, whose mission is to discover, develop and provide individualized experimental antisense oligonucleotide (ASO) medicines for nano-rare patients (1 to 30 patients with the same mutation worldwide) for free, for life. COO Sarah Glass presented on organizational progress with identifying optimal ASOs for development, ongoing optimization of R&D processes to extend the value of donations to more patients, and finally, promising data from nLorem’s first 173 applications. There are currently more than 90 patient programs in development and six approved INDs.  As demand continues to increase, future plans include expansion into EU countries.
• Shortening the diagnostic odyssey. It takes an average of 8 years for a rare disease patient to receive a clinical diagnosis. Organizations such as EveryLife Foundation for Rare Diseases and GeneDx are committed to shortening that timeline through increased funding and universal access to newborn genetic screening through collaboration with health systems, including Medicaid programs.
• The longer-term impact of the Inflation Reduction Act continues to fuel explosive debate, especially as many participants weighed in on the issue of squelching innovation. Rare disease advocates are united in the belief that the timelines for patent protections are insufficient, as ongoing research for approved medicines should be incentivized. In his keynote address, FDA Commissioner Rob Califf suggested “there’s always repair work to be done following big legislation” but stopped short of discussing specific regulatory or legislative actions in the works.
• Diversity and inclusive research rely on community engagement and investment. Priscilla Rodriguez from EveryLife Foundation for Rare Diseases urged the audience to consider funding opportunities for youths within communities targeted for research, including STEM education, and support for national awareness campaigns to promote research resources as well as genetic testing and counseling. Curt Oitman of Fulcrum Therapeutics offered examples of bring research to the community, using local phlebotomists and community-based clinics.
• Integration and normalization of mental healthcare into routine clinical practice both in everyday disease management and drug development was a hot topic among WODC attendees, with several lively discussions on the “why and how” of mental health support in this capacity. The opening keynote address delivered by renowned psychologist and rare disease dad Al Freedman from Rare Counseling, highlighted the challenges he faced as a rare father, and his work with the rare community today. The topic was further emphasized in the event program with a roundtable hosted by Frank Riviera from Stronger than Sarcoidosis, who after his own mental health struggles living with sarcoidosis, enabled a collaboration with online counseling providers to offer heavily discounted rates to rare patients. He has secured assurance from two major pharmaceutical companies to include counselors in future clinical trials as standard. As the mental health lead for Global Genes, it was incredible to see the positive movements in this space!

Finally, no rare disease gathering would be complete without hearing about the lived experiences from patients and caregivers. WODC did not disappoint in this space. Other compelling stories, video testimonials and calls to action from Marissa Penrod of Team Joseph, Kim Stephens of Muenzer MPS Research & Treatment Center and others reminded us of all why rare disease development investment and ongoing collaboration with patients and their caregivers are urgently needed. I am always proud to represent Parexel at WODC, a mission-focused organization whose unwavering commitment to patient-led rare disease drug development, combined with global scale, is driving transformational change in our industry.

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