In the United States, Orphan Drug designation is granted by the FDA to drugs focused on the treatment, prevention, or diagnosis of rare conditions; these are those affecting fewer than 200,000 citizens within the country. The designation is designed to incentivize the development of therapies for rare conditions. Along with this designation comes benefits such as tax credits, fee waivers, and seven years of market exclusivity. As reported by EMPR, Ketarx (racemic ketamine), designed for patients with Rett syndrome, recently earned this designation. 

Preclinical studies have shown that ketamine extended lifespan in male mice with Mecp2 mutations; in female mice, ketamine improved sensorimotor function and reversed Fos expression abnormalities. Currently, PharmaTher (the developer of Ketarx) and the FDA are using safety and efficacy data from a Phase 2 study to determine whether a Phase 3 study should be initiated. 

Ketarx is described by PharmaTher as being a ketamine hydrochloride injection USP product. Outside of Rett syndrome, Ketarx has also received Orphan Drug designation for complex regional pain syndrome (CRPS), amyotrophic lateral sclerosis (ALS), ischemia-reperfusion injury from organ transplantation, and status epilepticus. 

What is Rett Syndrome?

Rett syndrome is a rare neurodevelopmental disorder which primarily affects girls, though it can and does affect boys as well. Nearly all cases of Rett syndrome result from MECP2 gene mutations. However, this mutation is still poorly understood. In Rett syndrome, children typically display normal development until 6-18 months old, at which point developmental regression and other symptoms may occur. Symptoms can include:

• Hypotonia (low/poor muscle tone)
• Tense and irritable disposition
• Sleep interruptions or difficulties 
• Difficulty feeding
• Jerky limb movements
• Diminished eye contact
• Walking on the toes
• Slowed brain growth leading to a smaller head
• Breathing abnormalities
• Unusual hand movements
• Scoliosis
• Problems with hand movements and muscle coordination
• Social anxiety
• Delayed or absent language skills
• Uncoordinated breathing
• Seizures 

There is no cure for Rett syndrome. Treatments are largely supportive and symptomatic, including anti-epileptics, behavioral therapy, speech therapy, and physical and occupational therapy.