Taysha stops developing a gene therapy amid debate over FDA’s stance on ultra-rare trials

Taysha Gene Therapies discontinued development of a neurodegenerative therapy after the FDA again insisted on a potentially impossible study, the company said Tuesday.

It’s yet another reminder of how difficult it is to bring medicines targeting ultra-rare conditions to market.

The Dallas-based company was seeking approval of a therapy aimed at giant axonal neuropathy (GAN), a condition that renders patients quadriplegic and is followed by early death. Taysha said its plans were dashed by the FDA requiring a randomized, placebo-controlled trial.

The company has said such a study likely wouldn’t be possible because there aren’t enough eligible patients. It’s an increasingly common scenario that has spurred debate over the regulations for ultra-rare treatments.

The FDA stipulated a placebo trial late last year. And in response, Taysha recently submitted additional clinical data that failed to persuade the agency to back off on the proposal, the company said.

Sean Nolan

“Following FDA feedback, we have made the decision to discontinue further development of the program due to challenges related to the feasibility of the study designs,” Taysha CEO Sean Nolan said in a news release.

Outside observers say the FDA is in a tough position. Approvals based on limited data could give false hope or, even worse, harm patients. But rare disease advocates say the agency isn’t showing enough flexibility.

“The entire GAN community is gravely disappointed,” said Lori Sames, the executive director of Hannah’s Hope Fund for GAN. “For a regulatory submission for an ultra-rare disease like GAN, it doesn’t get any better than what was submitted.”

Her daughter, Hannah, who was diagnosed with GAN, received the therapy in a clinical trial seven years ago. The 19-year-old can now stand with help, and she lives a happy life filled with music and friends.

The therapy slowed the disease, Sames said, but it’s not a cure and an additional therapeutic is in development.

Astellas, which had an exclusive option to license the Taysha therapy, declined to do so. Taysha said it would pursue “external strategic options.”

The FDA hasn’t required a placebo-controlled trial in certain circumstances. But Taysha’s therapy is viewed as an early test in how the agency treats gene therapies targeting the rarest of rare diseases.

Nicole Paulk

Nicole Paulk, assistant professor of gene therapy at the University of California, San Francisco and the CEO of Siren Biotechnology, said early-stage companies that are exploring whether to invest in ultra-rare conditions are likely paying close attention to the FDA’s stance on the therapy.

“I can’t imagine that sitting in a boardroom right now that that wouldn’t be something that gets brought up,” Paulk said. “It could factor into a decision, but even then I’m not hearing any whispers or anything out there in the greater community.”

Taysha has now ceased development on all but one of its more than 20 programs, making it a poster child for wider commercialization challenges in therapeutics for ultra-rare conditions. Last summer, Taysha blocked families from restarting shelved programs elsewhere.

While the FDA’s feedback could ripple out into broader drug development, the financial impact appears limited for Taysha. The company’s stock was trading at $3.09 Wednesday morning, down 5% from the previous day.

However, analysts say the company’s value is largely wrapped up in its remaining program: a gene therapy for Rett syndrome. The disease causes missed developmental milestones and eventually a loss of critical skills.

Last month, Taysha shared data from one patient who received the therapy and also raised $150 million from a private placement.

With the discontinuation, Taysha said its cash runway now extends into the fourth quarter of 2025.

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