Avlayah is the first Hunter syndrome therapy approved to address the condition’s neurologic complications, according to Tracy Beth Høeg, acting director of the Center for Drug Evaluation and Research.
The FDA has granted accelerated approval to Denali Therapeutics’ enzyme replacement therapy for Hunter syndrome, handing a much-needed win to the rare disease market. The drug will carry the brand name Avlayah.
Wednesday’s approval for Avlayah delivers several firsts for the industry. The therapy is the first new medicine for Hunter syndrome in nearly 20 years, Denali said in its press announcement on Wednesday, adding that Avlayah is the first FDA-approved biotherapeutic that uses the transferrin receptor to cross the blood-brain barrier.
Avlayah is also “the first product approved to address neurologic complications of Hunter Syndrome,” according to Tracy Beth Høeg, acting director of the Center for Drug Evaluation and Research. Full approval of Avlayah will hinge on the findings of a confirmatory trial designed to verify its clinical benefits.
Denali closed Wednesday’s trading session at $22.47 apiece, up 13% from its previous closing price.
The approval is also a “welcome positive” for the broader rare disease space, Stifel analysts said in a Wednesday note.
Indeed, the past few months have brought a string of bad news for rare disease drugmakers, driven by inconsistencies and perceived inflexibilities at the highest levels of the FDA. One recent example is that of uniQure, which in November 2025 announced that the regulator changed its tune regarding the development of the company’s Huntington’s disease gene therapy.
The agency at that time told uniQure it “no longer agrees” that data from the company’s Phase 1/2 program would be enough for a filing, despite allegedly previously signing off on the study design. The about-face triggered months of back-and-forth, playing out in the public sphere.
Around 500 patients in the U.S. have Hunter syndrome, a rare, genetic disease that predominantly affects boys and manifests as cognitive delays, behavioral issues and hearing loss. The disease is caused by mutations to the IDS gene resulting in a faulty enzyme that, in turn, leads to accumulation of toxic byproducts across multiple organs and tissues, including the brain.
Avlayah works by supplying patients with enough IDS enzyme. Importantly, the drug makes use of Denali’s proprietary TransportVehicle platform, which relies on the transferrin receptor to cross the blood-brain barrier into the central nervous system. This sets it apart from Takeda’s Elaprase, another enzyme replacement therapy for Hunter syndrome, initially approved in 2006.
Phase 1/2 data for Avlayah, which served as the basis for Wednesday’s approval, showed that the drug led to a 91% reduction in levels of heparan sulfate in the cerebrospinal fluid, a key disease marker that is “reasonably likely to predict clinical benefit,” according to Denali’s news release.
At 24 weeks, 93% of patients treated with Avlayah had heparan sulfate levels comparable to people without Hunter syndrome.
For many analysts, Avlayah’s approval derisks Denali’s technology. The FDA’s greenlight “provides a key validation for the company’s differentiated TransportVehicle chemistry for CNS delivery,” which could have promising readthrough to the rest of its pipeline, analysts at William Blair told investors on Wednesday. The firm forecasts peak U.S. Avlayah sales of over $250 million in the late 2030s, with worldwide revenue approaching $1 billion.
Stifel agreed with this assessment, calling the nod a “key milestone” for Denali.
On Feb. 10, the FDA rejected REGENXBIO’s gene therapy for Hunter syndrome—a decision that put Denali in a good spot—citing concerns over the company’s use of natural history controls to gauge the efficacy of its products, a design feature that REGENXBIO said the FDA had previously agreed to. The FDA also pointed to problems with REGENXBIO’s eligibility criteria for patient enrollment and the validity of the biomarker it used.
REGENXBIO, which had thought it had addressed the FDA’s concerns prior to receiving the complete response letter last month, has stated its plans to request a Type A meeting with the FDA to discuss the rejection and a possible resubmission.
