Marvel to seek FDA’s orphan drug status for MB-204 in Rett
Developer will use designation, if granted, to advance therapy to clinic
Marvel Biosciences plans to ask the U.S. Food and Drug Administration (FDA) to grant orphan drug status to its MB-204 treatment candidate for Rett syndrome — with the goal of helping advance the therapy toward clinical studies.
This designation is granted by the FDA to incentivize the development of new treatments for rare diseases, or those affecting fewer than 200,000 people in the U.S.
The status comes with various benefits for developers, including tax credits for clinical trials, exemptions from regulatory fees, and seven years of market exclusivity should the treatment eventually be approved. It also offers access to other programs that can help accelerate the approval process, according to Marvel.
Marvel decided to apply for the designation given new preclinical data demonstrating MB-204’s benefits in social behavior in a mouse model of Rett. Should the FDA grant the request, Marvel will use the orphan drug status to accelerate MB-204’s clinical development, the company said in a press release.
“Orphan drug designation will help validate MB-204’s potential in Rett syndrome,” said Rod Matheson, Marvel’s CEO. “This designation would provide essential support as we work to bring this much-needed treatment to patients.”
Developer says positive MB-204 preclinical data support orphan drug status
Rett syndrome is a rare neurodevelopmental disease affecting mostly girls. Most cases are caused by mutations in the MECP2 gene that ultimately affect the activity of other genes important for brain development and function.
Patients may initially show normal development, but generally start to regress between 6 and 18 months of age. The disease typically leads to motor, cognitive, and speech problems, as well as autism-like features — including issues with social interaction — among its other symptoms.
MB-204 is a derivative of istradefylline, a medication that’s approved in the U.S. for treating Parkinson’s disease under the brand name Nourianz. It works by blocking activity at adenosine A2a receptors, which normally mediate the effects of a brain-signaling chemical called adenosine.
Disturbances in adenosine signaling have been implicated in a number of neurological diseases. Thus, targeting this system has been proposed as a potential therapeutic approach for such conditions, including Rett.
According to Marvel, MB-204 is designed to work faster, more effectively, and at lower doses than existing treatments.
The preclinical experiments that evaluated the therapy in Rett were done in a mouse model of the disease, conducted in collaboration with the International Institute for the Brain.
Mice were treated daily for two weeks with either MB-204 or Daybue (trofinetide) — the only approved therapy for Rett in the U.S. and Canada.
Marvel reported initial data late last year indicating that MB-204 restored more normal social interactions in the mouse model — generally outperforming Daybue — with benefits that persisted for weeks after treatment ended.
Given the encouraging data from our [preclinical] study, we see a strong case for MB-204 to follow a similar regulatory path [to Daybue].
The company recently reported part of the final data from the study. Those results showed that MB-204 reversed deficiencies in key behavioral outcomes, including measures of social behavior and interaction, memory, and repetitive behaviors. The experimental therapy significantly outperformed Daybue across multiple measures.
Final analyses of the carry-over effects of the two treatments — their sustained benefits even after treatment was stopped — are ongoing, per Marvel.
“We are very pleased with these results and excited to take the next step in seeking orphan drug designation,” said Mark Williams, PhD, Marvel’s chief science officer.
Daybue also had earned orphan drug status prior to its own U.S. approval. “Given the encouraging data from our study, we see a strong case for MB-204 to follow a similar regulatory path,” Williams said.
Marvel also is looking at MB-204 as a possible treatment for other neurological conditions, such as fragile X syndrome and Alzheimer’s disease.
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