From Awareness to Acceleration: Rare Disease Drug Development Enters a Pivotal Era

The future for rare disease drug development looks bright, as noted in company presentations at the recent J.P. Morgan Healthcare conference, and recent FDA initiatives to facilitate regulatory pathways.

The timing allays well with the 18^th anniversary of Rare Disease Day, on February 28. The date anchors Rare Disease Month. The campaign was started by The Europe Organisation for Rare Diseases, which focuses on advancing research, improving diagnosis and supporting patients.

Since Rare Disease Day launched in 2008, investor interest in rare diseases has grown from a niche bet to a billion-dollar market, underpinned by orphan drug economics and the rise of cell and gene therapies (CGT).

Analysts estimate the global rare disease treatment market at roughly $220–240 billion in the mid2020s, with annual growth anticipated to bump it into the $400–600 billion range by the early-to-mid 2030s.

As BioSpace previously reported, rare and chronic diseases headlined investor and R&D interest at JPM26. Company executives during presentations on the third conference day, such as by Rocket Pharmaceuticals, REGENXBIO and Kyverna Therapeutics, declared 2026 to be a pivotal year.

A flurry of FDA’s 2025 guidances focused on accelerating the path of CGTs to the market—particularly those intended for rare and ultrarare diseases— bolstered industry confidence.

The agency also introduced in November the plausible mechanism approval pathway for rare diseases, intended to expedite treatments “for products where a randomized trial is not feasible.” This followed the Rare Disease Evidence Principles framework in September to expedite the approval of therapies for ultrarare diseases, usually those affecting less than 1,000 people in the U.S.

“I view these programs as a net positive for rare diseases; more specifically, cell and gene therapies for rare diseases in which the mechanism is genetically defined and well characterized,” said Sean Ainsworth, CEO of Immusoft, which is developing a CGT for the ultrarare condition mucopolysaccharidosis type II (MPS II).

MPS II, also known as Hunter syndrome, is caused by a deficiency of the enzyme iduronate-2-sulfatase (IDS). The disease primarily affects pediatric patients and is associated with progressive, multisystem involvement and reduced life expectancy. The current standard of care is enzyme replacement therapy (ERT), which requires frequent lifelong infusions and may not achieve consistent enzyme exposure across all affected tissues.

REGENXBIO’s clemidsogene lanparvovec works by delivering a functional copy of the IDS gene. The therapy has a February 8 FDA Prescription Drug User Fee Act date by which the FDA must make an approval decision.

Immusoft positions engineered B cells as a redosable, in vivo enzyme factory platform instead of lifelong ERT. Its investigational therapy, ISP-002, “is designed to deploy a patient’s own B cells as long-lived protein biofactories capable of continuously producing and secreting therapeutic levels of IDS,” according to a press release. “By leveraging the natural biology of B cells and their ability to engraft in the bone marrow, ISP-002 is intended to enable sustained systemic enzyme exposure following a single treatment.”

There are significant burdens for ERTs in terms of weekly infusions, said Ainsworth. In addition, as ERTs have a short half-life in the plasma of only 2-3 hours, therapeutic exposure to the tissues is minimal. ISP-002 rather is intended to be a “24/7 therapeutic protein.”

Many gene therapies are adeno-associated virus (AAV) vector-based, so the body typically mounts an immune response when injected, Ainsworth said. But using the patient’s own B cells is a nonviral approach, eliminating a potential immune response and allowing for patient redosing, he added.

On January 26 and December 15, the company announced it had received FDA’s Rare Pediatric Disease Designation for ISP-002 and Orphan Drug Designation, respectively.