According to a recent press release from biopharmaceutical company Praxis Precision Medicines (“Praxis”), two of the company’s drug candidates received either Orphan Drug or Rare Pediatric Disease designations for rare developmental and epileptic encephalopathies. While PRAX-222, designed to treat SCN2A developmental and epileptic encephalopathy (SCN2A-DEE), received Rare Pediatric Disease and Orphan Drug designations, PRAX-562, designed for SCN2A-DEE and SCN8A developmental and epileptic encephalopathy (SCN8A-DEE), received Rare Pediatric Disease designation.

PRAX-222 and PRAX-562

While these drugs are currently being looked at for SCN2A-DEE and SCN8A-DEE, they were developed to treat a variety of central nervous system disorders. PRAX-222 is an antisense oligonucleotide. In an article published in Nature Review Neurology, Carlo Rinaldi and Matthew J.A. Wood describe antisense oligonucleotides as:

short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms.

In this case, PRAX-222 works to reduce SCN2A proteins to help reduce severe epilepsy in patients with SCN2A-DEE. Alternately, PRAX-562 is a small molecule sodium current blocker. Its safety, efficacy, and tolerability is being tested within a Phase 1 clinical trial.

Rare Pediatric Disease Designation

Drug developers may receive Rare Pediatric Disease designation for their products if these therapies are designed to treat rare conditions or diseases in patients under 18 years old. Rare diseases are defined as those affecting under 200,000 American citizens. According to the FDA:

Under Section 529 to the Federal Food, Drug, and Cosmetic Act (FD&C Act), FDA will award priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. Under this program, a sponsor who receives an approval for a drug or biologic for a “rare pediatric disease” may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.

Orphan Drug Designation

This designation is granted to therapies designed to treat rare diseases. As described above, a rare disease or condition is defined as one affecting under 200,000 Americans. This program was developed to facilitate investigational treatments for patients with rare diseases. If a company’s drug is given Orphan Drug designation, said company receives tax credits, assistance with research costs, and 7 years of market exclusivity.

SCN2A-DEE and SCN8A-DEE

The FamilieSCN2A Foundation explains:

SCN2A is one of the genes most commonly associated with early-onset epilepsy, and has recently been linked to autism spectrum disorder and developmental delay. SCN2A encodes a neuronal voltage gated sodium channel, NaV1.2 that is primarily found in excitatory neurons throughout the brain.

SCN2A-DEE and SCN8A-DEE are both relatively similar disorders; the difference is that the former is caused by SCN2A mutations and the latter by SCN8A mutations. These rare developmental and epileptic encephalopathies cause frequent, recurring, and treatment-resistant seizures. In many cases, these seizures begin at birth. Other symptoms include:

• Extremely high or extremely low heart rate
• Low muscle tone
• Intellectual and cognitive disabilities
• Impaired coordination
• Involuntary muscle contractions
• Cyanosis (bluish discoloration of the skin)
• Status epilepticus
• Feeding difficulties
• Gastrointestinal distress