First Fragile X Treatment on Cusp of Clinical Trials

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The highlighted portion shows the mutated X chromosome, which causes FXS. The highlighted portion shows the mutated X chromosome, which causes FXS.

Living with Fragile X Syndrome (FXS) can be crippling for a family emotionally, financially and physically; the rare disorder disrupts the skills needed for everyday life, such as thinking, talking and self-care. Indianapolis-based Confluence Pharmaceuticals LLC is aiming to restore hope and unlock potential for FXS patients and is just weeks away from launching Phase 1 clinical trials of its drug. It could mark a major turning point for FXS families, who currently have no treatment options that address the disability’s core impairments.

While FXS is considered a rare disorder, affecting about 180,000 people in the U.S., it’s the leading known cause of Autism Spectrum Disorder (ASD), and about half of FXS patients have autism. In other words, ASD and FXS frequently occur together. Patients with FXS are considered intellectually disabled. FXS characteristics include language, social and learning impairments. Patients often struggle with social behavior, inattention, hyperactivity, mood disorders, anxiety and aggression.

“It’s not unusual for these kids to be taking anywhere from three to five different drugs to alleviate some of the interfering impairments that they have, such as anxiety or irritability,” says Confluence Pharmaceuticals President Steven Johns. “It’s a complex disorder to solve. As far as treatment of the core symptoms, there’s nobody that’s gotten [drug] approval yet.”

Confluence believes it could be the first. Its drug, called Acamprosate, will begin Phase 1 clinical trials in a few months. The startup says it’s the first treatment that addresses the core social and communication impairments. Acamprosate was originally used for cessation from alcohol; Dr. Craig Erickson discovered the drug's application for FXS in 2009 during his time at the Indiana University School of Medicine.

“We’ve had some remarkable stories come from the field—children who were nonverbal who became verbal and started talking,” says Johns. “They’d been learning the words all along, but just never could get them out. Those stories do restore hope for families to potentially start toward a path of normalization.”

The drug is meant for pediatric patients; Confluence believes starting treatment as early as possible can increase the long-term potential of the individual. Johns says Acamprosate is showing the most significant improvements in addressing hyperactivity, anxiety, social behavior and communication. The startup has spent the last two years perfecting the “old compound” it originally planned to send through the approval process.

“The amount of the [old] drug that was actually getting into the human blood was very low—around 11 percent. We were able to significantly improve that,” says Johns. “That means they don’t have to take as much drug to get the same impact; that was a major finding from our perspective.”

The startup also reevaluated the drug’s mode of delivery; because FXS patients often have sensory and mechanical issues that cause eating and swallowing problems, Confluence converted its drug to a “sprinkle” formulation that could be integrated with a child’s favorite foods.

The startup has raised $1.3 million in funding and is working to scale up the manufacturing process. Johns says Confluence is now expanding the way it views treatment for FXS.

“We’re looking for other compounds we might put with Acamprosate and have patented another set of compounds we’ll bring forth in our development cycle as well,” says Johns. “It’s a little broader than FXS; we think it has the ability to treat some cognitive impairments, particularly in the areas of memory and learning.”

Now “on the back side” of product development, Johns says Confluence aims to deliver the first comprehensive treatment option that could bring hope to families and unlock the potential of patients living with FXS.

“Individuals who have significant impairments becoming more normalized in terms of their ability to socially interact with their parents or with others—it’s an important thing we all take for granted. Having your child be able to go to school, for example, and start learning, that’s somewhat of a miracle,” says Johns. “It’s kind of like the ribbon at the end of the race; we’re getting closer. We’d love to cross that line.”

Johns says Confluence’s drug was nearing clinical trials in 2015 when the startup decided to “take a step back” before bringing it to market.
Johns says the basic concept of asking parents for their input revealed that a “sprinkle” form would be the best method for FXS patients to take the medication.
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