RARE Daily

FDA Grants Rare Pediatric Disease Designations to Inversago and to Praxis Precision Medicines

January 7, 2021

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease designation to Praxis Precisions Medicines for two different experimental therapies to treat rare developmental and epileptic encephalopathies and separately to Inversago Pharma for its experimental therapy to treat Prader-Willi syndrome, a genetic disease that causes obesity.

The grants to Praxis cover drugs to treat SCN2A-DEE and SCN8A-DEE, both of which are rare developmental and epileptic encephalopathies caused by variants in different genes. Both the SCN2A and SCN8A genes are critical in the formation of sodium channel proteins in the brain, which control the flow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. Patients suffer from recurrent, typically drug-resistant seizures which start as early as the first day of life. The seizures can be of multiple different types, up to dozens per day, with poor response to current treatment options.

Patients with SCN2A-DEE and SCN8A-DEE have significant cognitive disabilities and can suffer from movement disorders and problems in other body systems. Those with SCN8A-DEE also may experience increases or decreases in heart rate, abnormal breathing, and cyanosis, a discoloration of the skin from inadequate oxygen in the blood.

The Rare Pediatric Disease grants were made to PRAX-222 for treatment of SCN2A-DEE and PRAX-562 for both SCN2A-DEE and SCN8A-DEE.

PRAX-222 is an antisense oligonucleotide that is designed to lower the expression levels of the protein encoded by the SCN2A gene in patients with SCN2A gain-of-function epilepsy. The program is ongoing under a three-way collaboration with Ionis Pharmaceuticals and RogCon and is currently being evaluated in IND-enabling studies.

PRAX-562 is a selective small molecule and is the first persistent sodium current blocker in development for the treatment of a wide range of rare CNS disorders. The clinical development plan for PRAX-562 involves exploring the broad potential for the mechanism of action in rare diseases through proof-of-concept trials in two rare types of cephalgia, and then expanding into a range of rare pediatric DEEs. PRAX-562 is currently being evaluated in a phase 1 clinical trial in adult healthy volunteers.

“The potential broad utility of PRAX-562 in DEEs and other rare CNS disorders and the precision therapy approach of PRAX-222 represent two differentiated and potentially complementary treatment paradigms inspired by human genetics,” said Steven Petrou, co-founder and chief scientific officer of Praxis. “The FDA granting these designations is an acknowledgement of the critical need to develop treatments for children living with these devastating diseases.”

Separately, the FDA granted Rare Pediatric Disease designation to Inversago Pharma’s lead compound INV-101, an experimental treatment for Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder, and the most common genetic cause of life-threatening childhood obesity. At an early stage, PWS is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. As the disorder progresses, affected children develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity, among other symptoms. The treatment of PWS is currently limited to managing symptoms of the disorder as they arise. To date, there is no cure or disease modifying treatment for this genetic disorder.

INV-101 is a first-in-class, small molecule CB1 inverse agonist / antagonist being developed by Inversago for the treatment of PWS and non-alcoholic steatohepatitis (NASH). It is specifically designed to interact with peripheral CB1 receptors located in the gastro-intestinal tract, liver, pancreas, adipose tissues, muscles, lungs and other organs, thus aiming for a safe and effective therapeutic approach without the known liabilities of centrally acting CB1 blockers. The peripheral CB1 blockade is a well-documented pathway, linked to many clinically meaningful metabolic benefits. A phase 1 study with INV-101 is currently ongoing to evaluate its safety, tolerability and pharmacokinetics profile.

“The RPD designation is an important recognition for Inversago, highlighting the potential role of our lead program in the treatment of young patients affected by Prader-Willi syndrome,” stated François Ravenelle, CEO and founder of Inversago Pharma.

The Rare Pediatric Disease designation is open to drug development programs targeting serious, life-threatening diseases that primarily affect less than 200,000 Americans aged 18 or younger. Once a new drug application is approved under this program, the company is eligible to receive a priority review voucher for any related marketing application.

The voucher, which reduces the standard review time for a new drug application by four months, is potentially lucrative because it is transferable. Most recently, Rhythm Pharmaceuticals sold a priority review voucher to Alexion for $100 million.

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