FDA grants RPDD to CSTI-500 for treating pediatric Prader-Willi Syndrome

FDA grants RPDD to CSTI-500 for treating pediatric Prader-Willi Syndrome | Image Credit: © wladimir1804 - © wladimir1804 - stock.adobe.com.

CSTI-500 has received a Rare Pediatric Disease Designation (RPDD) from the FDA for the treatment of Prader-Willi Syndrome (PWS) in pediatric patients, according to ConSynance Therapeutics, Inc.¹

Approximately 1 in 15,000 live births are impacted by PWS, a genetic neurodevelopmental disorder that presents as severe hypotonia and failure to thrive evolving into life-threatening hyperphagia in early childhood. PWS can also lead to other debilitating neuropsychiatric behaviors such as severe temper outbursts.

Obesity is an underlying cause of multiple complications associated with PWS, according to Mayo Clinic.² Patients with PWS will often experience a constant sense of hunger starting at the age of 2 years, and management often requires a team approach including multiple specialists.

Additional symptoms of PWS include poor muscle tone, distinct facial features, poor sucking reflex, poor responsiveness, and underdeveloped genitals. As children with PWS age, they may also experience food craving and weight gain, underdeveloped sex organs, poor physical development, cognitive impairment, sleep disorders, and speech problems.

The exact mechanism behind PWS has not been identified, but data has linked the condition to genes located in a region of chromosome 15. Either paternal genes on chromosome 15 are missing, the child inherited 2 copies of chromosome 15 from the mother and none from the father, or there is a defect in paternal genes on chromosome 15.

Patients with PWS and their families face significant challenges, but there is no therapy focusing on the core dysfunction brain networks behind neuropsychiatric PWS behaviors with approval in the United States.¹ A therapy normalizing these neurotransmitters may alleviate behavioral symptoms impacting patients and their families.

ConSynance is focused on the development of first-in-class therapies for rare central nervous system disorders. Its partnership with Harmony Biosciences to treat multiple rare neurological diseases highlights the company’s drive to develop effective therapies for patients in need.¹

CSTI-500 is a first-in-class, orally administered Triple Monoamine Reuptake Inhibitor designed to increase serotonin, dopamine, and norepinephrine levels in the synaptic clefts of neurons. These are vital neurotransmitters associated with many neuropsychiatric disorders.

Certain inhibitors have been approved for the management of conditions such as obsessive compulsive disorders, attention deficit hyperactivity disorder, and more. This has led investigators to predict that CSTI-500 would be effective in managing PWS and other neuropsychiatric indications.

In 3 phase 1 clinical trials, the safety and efficacy of CSTI-500 has been evaluated in nearly 100 human participants. A phase 2 trial is set to be conducted in 2025.¹

Rare pediatric conditions are defined by the FDA as those impacting under 200,000 US individuals but are serious or life-threatening, and mainly present in pediatric patients. With the RPDD designation, ConSynance can receive a transferable Priority Review Voucher if CST-500 receives FDA approval for PWS.

The current worth of Priority Review Vouchers is approximately $100 million, indicating their value for facilitating a drug’s development. According to the FDA, the Priority Review Voucher program was designed to incentivize the development of drugs for rare pediatric diseases.³

RPDDs are given to products that meet certain criteria, and the FDA has stated, “We will strive to respond to each rare pediatric disease designation request within the applicable review timeline.” The designation may be requested for a drug prior to submission of a marketing application.

Reference

1. ConSynance therapeutics announces US FDA grants rare pediatric disease designation to CSTI-500, a potential first-in-class therapy for Prader-Willi Syndrome. ConSynance Therapeutics. July 24, 2024. Accessed July 25, 2024. https://www.globenewswire.com/news-release/2024/07/24/2918161/0/en/ConSynance-Therapeutics-Announces-U-S-FDA-Grants-Rare-Pediatric-Disease-Designation-to-CSTI-500-a-Potential-First-in-Class-Therapy-for-Prader-Willi-Syndrome.html
2. Prader-Willi syndrome. Mayo Clinic. Accessed July 25, 2024. https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997
3. Rare pediatric disease designation and priority review voucher programs. US Food and Drug Administration. Accessed July 25, 2024. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs#About