Hunter Syndrome Approval Shows How Rare Pediatric Disease Vouchers Work

Denali Therapeutics said on March 25 that the Food and Drug Administration had granted accelerated approval to Avlayah (tividenofusp alfa-eknm), an enzyme replacement therapy for the neurologic manifestations of Hunter syndrome, or mucopolysaccharidosis type II, in children weighing at least 5 kg before advanced neurologic impairment. In its release, filed with the Securities and Exchange Commission, the company said the approval was based on a reduction in cerebrospinal fluid heparan sulfate as a surrogate endpoint, and that continued approval may depend on a confirmatory Phase 2/3 trial.

The company also said FDA granted it a Rare Pediatric Disease Priority Review Voucher with the approval. The voucher "may be used to obtain priority review for a future marketing application or transferred to another sponsor," Denali said. It did not say whether it plans to use or sell it.

What earns a voucher

The program is set out in section 529 of the Federal Food, Drug, and Cosmetic Act, codified at 21 U.S.C. 360ff. A rare pediatric disease is one that is serious or life-threatening, with serious or life-threatening manifestations that primarily affect people from birth to age 18, and that is also a rare disease or condition. That second term comes from the orphan drug law, 21 U.S.C. 360bb, which defines it mainly as a condition that affects fewer than 200,000 people in the United States.

The approved application must be for a drug or biologic that prevents or treats such a disease and, for a drug, contain no active moiety previously approved. The sponsor has to tell FDA when it submits the application that it intends to request a voucher.

What a voucher is worth

The voucher is not for the approved drug. It entitles the holder to priority review of a different future application, which the statute defines as FDA review and action within six months of receipt. The holder must notify FDA at least 90 days before submitting that application and pay a separate priority review user fee, which FDA sets each fiscal year.

The statute says the sponsor may transfer the voucher, "including by sale," and that "There is no limit on the number of times a priority review voucher may be transferred before such voucher is used." Each new owner must notify FDA within 30 days. FDA may revoke a voucher if the rare pediatric disease product is not marketed in the US within 365 days of approval.

That transferability gives the vouchers resale value. A client alert from law firm Lowenstein Sandler said vouchers have traded on a secondary market for hundreds of millions of dollars, making them a source of nondilutive funding for smaller sponsors.

A program that lapsed and returned

The voucher program began in 2012, entered a sunset period and lapsed at the end of 2024, according to Lowenstein. The Consolidated Appropriations Act, 2026, signed on Feb. 3, revived it, incorporating provisions from the Mikaela Naylon Give Kids a Chance Act. The statute now says FDA may not award rare pediatric disease vouchers after Sept. 30, 2029.