Orphan Drugs, Expedited Programs & Regulatory Flexibility

We help sponsors develop drugs and biologics for rare diseases and other serious diseases with unmet need. These programs require deliberate planning around regulatory flexibility, expedited programs, evidentiary standards, and patient need, often well before the first IND. We work with sponsors to think through uncertainty, anticipate where review divisions will push back, and identify the FDA precedents and policies most likely to support the program. Our approach is grounded in close engagement with patient communities and review teams, careful framing of the development plan, and judgment about when and how to ask FDA to exercise the flexibility available under its authorities.

We advise on:

• Orphan drug designation and orphan drug exclusivity
• Clinical superiority assessments and second-in-class orphan development strategy
• FDA designations: breakthrough, fast track, priority review, RMAT, platform technology
• Accelerated approval and Subpart E/H, including confirmatory trial design
• Priority review vouchers (PRVs): rare pediatric, tropical, medical countermeasure
• Regulatory flexibility, including on small or novel trial designs, single-study and plausible hypothesis pathways, flexible evidentiary standards
• External controls, natural history, real world evidence
• FDA development and review initiatives, including expedited review mechanisms, rare-disease pilots, real-world evidence, AI/ML and digital health tools, model-informed development, and innovative trial designs

Selected Experience

• Obtained successful orphan drug designation after two prior rejections, including through a meeting with OOPD.
• Worked with a sponsor and patient organization to secure IND authorization for an investigational 1-of-1 therapy, overcoming FDA concerns regarding available nonclinical and quality data.
• Leveraged PFDD testimony, patient data, and unmet need to draft a successful breakthrough therapy designation.
• Helped a sponsor secure a tropical disease priority review voucher for a tropical disease not originally listed on the qualifying list of tropical diseases through extensive FDA and patient engagement.
• Worked closely with management, regulatory, medical, quality, and external consultants over a yearslong engagement on a rare disease program on planning, execution, and overcoming challenges, leading to accelerated approval based on Phase 1/2 data.
• Helped sponsor overcome review team concerns regarding magnitude of benefit and use of an intermediate clinical endpoint, leading to successful accelerated approval.