Acadia Wins FDA Approval for First Rett Syndrome Medicine

Pictured: Kathie Bishop, Ph.D./courtesy of Acadia Pharmaceuticals

Pictured: Kathie Bishop, Ph.D./courtesy of Acadia Pharmaceuticals

Acadia Pharmaceuticals didn't have to wait until March 12 to find out that trofinetide had been approved as the first therapy for Rett Syndrome. The FDA instead delivered the news late Friday evening.  

“Now, for the first time after decades of clinical research, healthcare providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome," said Jeffrey L. Neul, M.D., Ph.D., professor at Vanderbilt University Medical Center and Phase III Lavender study investigator, in a prepared statement.   

Acadia will market the drug as Daybue and expects it to be available in the U.S. by the end of April 2023. 

The company secured a Rare Pediatric Disease Priority Review voucher along with the approval. 

Acadia developed Daybue in partnership with Neuren Pharmaceuticals.

Speaking with BioSpace ahead of the decision, Kathie Bishop, Ph.D., SVP and head of rare disease and external innovation at Acadia, said that if approved, trofinetide would also be the first drug approved to treat any neurodevelopmental disorder.  

Rett syndrome is a multisystem neurodevelopmental disorder characterized by developmental regression, loss of language and hand function and impaired gait.

It affects primarily female children, who develop normally until around the age of two, when they begin to miss expected milestones. They also begin to lose function, most notably verbal abilities and the ability to control hand function.

Bishop said that while the disease affects neurons throughout the brain, it is not neurodegenerative.

“What happens is that the connections between the brain cells are lost, so you still have the neurons there, but they can't communicate with each other.” 

Trofinetide restores those connections between cells, Bishop said.

Because the disease is not neurodegenerative, Bishop said there is potential to intervene at any age. In clinical trials, Acadia saw improvements in both younger and older patients.

The Lavender Trial 

Daybue, a novel synthetic analog of the amino‐terminal tripeptide domain of the IGF-1 protein, was assessed in the Phase III Lavender study. A 12-week study, Lavender compared the drug against placebo in 187 girls and young women between five and 20 years of age.

The co-primary endpoints, change in Rett Syndrome Behavior Questionnaire scores from baseline and Clinical Global Impression-Improvement scale score, were significantly improved after treatment with Daybue compared to the control group.

Bishop shared that what parents mention most often is that their children can’t communicate with them.

Throughout clinical trials, she said Acadia saw an improvement in, particularly, non-verbal communication.

“Parents talk about [how] the girls kind of become more awake. They're able to interact. They're able to indicate what they want,” she said. Acadia has also seen improvement in motor function.

While the study did not include any boys, Bishop said that based on trofinetide’s mechanism, there is no reason to think the drug wouldn’t also help this minority patient population.

A Reputation for Firsts

With the approval, Daybue becomes Acadia’s second commercial product. It is also its second novel approval. In May 2016, the FDA greenlit Nuplazid (pimavanserin) as the first treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. 

Acadia is currently studying pimavanserin in a Phase III trial for the negative symptoms of schizophrenia, another indication for which there is currently no approved drug. In this space, Acadia is competing with Karuna Therapeutics’ KarXT. Karuna has stated it plans to submit for approval of KarXT by mid-2023. 

Bishop has devoted 20 years of her career to the study of rare, neurological diseases, and she said this is a very exciting time in the space.

“On the clinical side, with the advances in genetic testing, patients are being more readily identified and studied. Then on the science side, I think [there are] a lot of great discoveries and advancements. I think this is just the beginning of a lot more to come in neurologic rare diseases, especially genetic diseases.”

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