Therapy Area Dynamics Mirror Non-Orphan Pipeline

Therapy area dynamics mirror non-orphan pipeline

Therapy area projections show oncology’s dominance under continued pressure from drugs for auto-immune, cardiovascular, blood and CNS conditions, as is the case across the wider pharmaceutical landscape. Cancer’s share of worldwide orphan drugs sales is projected to drop from almost 40% in 2025 to 33% in 2032, as immunomodulators, CNS, CV and neuromuscular disease drugs gain.

Figure 8: Share of Worldwide Orphan Drug Sales by Therapy Category and Lead Companies,
2025 and 2032

The rise of these therapy areas is also reflected across biopharma dealmaking, with transactions like Novartis’ $12 billion Avidity Biosciences purchase in October 2025, focused on rare neuromuscular disease candidates, or J&J's January 2025 acquisition of CNS-focused Intra-Cellular Therapies, worth $14.6 billion.

Mixed messages from FDA

FDA’s ‘plausible mechanism pathway’ for personalized and niche drugs outlines a flexible, common sense-based approach in line with FDA’s “broader de-regulatory agenda”¹⁰. Draft guidance released in February 2026 provides more detail on how the agency might consider individualized drugs targeting specific genetic mutations known to cause certain ultra-rare diseases. Because the gene-editing component of, say, CRISPR-based therapies is specific to particular DNA sequences, products targeting different parts of the same gene might be evaluated as a single application with a single supporting trial. This ‘master protocol’ approach should expedite access to therapies for patients with a wider range of mutations than might directly feature in a supporting trial¹¹.

Yet the regulator in 2025 also rebuffed several rare disease drugs, including Capricor Therapeutics’ cell therapy deramiocel for Duchenne muscular dystrophy-related cardiomyopathy and Biohaven’s troriluzole for spinocerebellar ataxia (SCA), citing trial design flaws.

Gene therapies have also had a rocky ride. The agency in November 2025 appeared to back-track on earlier trial design advice for uniQure’s Huntington’s gene therapy candidate, declaring that the company’s Phase 1/ 2 data was no longer sufficient to support a submission. In early 2026, it rebuffed Regenxbio’s Hunter syndrome therapy due to use of a surrogate biomarker and a natural history control arm. (The candidate had previously faced a clinical hold.)

FDA also in early 2026 turned down one of the first awardees of a National Priority Review voucher, Disc Medicine’s bitopertin, due to questions around use of a surrogate biomarker. The rebuttal followed several months of positive feedback, according to analysts. Voucher candidate selection criteria are already unclear, beyond broad categories including ‘delivering innovative or breakthrough cures with novel mechanisms’ (the most relevant to orphans), ‘addressing a US health crisis’, and increasing affordability. Bitopertin is in development for a rare blood disorder called erythropoietic protoporphyria.