Treatment for Angelman syndrome gets FDA’s orphan-drug designation

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Image: College of Veterinary Medicine & Biomedical Sciences

The U.S. Food and Drug Administration has granted orphan-drug designation to GTX-101 for the treatment of Angelman syndrome, a rare neurogenetic disorder that affects approximately 1 in 15,000 people. GTX-101 is the first drug candidate for startup GeneTx Biotherapeutics, LLC (GeneTx).

“No approved treatments for Angelman syndrome exist today,” said Allyson Berent, GeneTx chief science officer. “The FDA’s orphan-drug designation for GTX-101 highlights the significant need for treatments for individuals with Angelman syndrome, and we believe that targeted delivery of GTX-101 represents a promising, novel approach to treat this devastating disorder.”

Angelman syndrome is caused by a loss of function of the maternally inherited UBE3A gene. Symptoms include developmental delay, impaired motor function, loss of speech and epilepsy.

GTX-101 is an investigational antisense oligonucleotide designed to inhibit transcription of the UBE3A-AS across the paternal allele of UBE3A. In vitro studies show that as a result of this inhibition, transcription of the paternal UBE3A gene is restored in neurons of the central nervous system.

An antisense oligonucleotide is a synthetic string of nucleic acids that interferes with the normal processing of a target gene to, for example, turn on or turn off expression of a target gene or to alter the splicing pattern of the gene. Clinical trials have shown promising results using antisense oligonucleotides to treat neurogenetic disorders for spinal muscular atrophy and amyotrophic lateral sclerosis.

“This is a new area of medicine, known as a targeted therapy,” said Scott Dindot, associate professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences. “Historically, clinicians have treated symptoms of a disease or disorder with medication but not the cause of the condition. A targeted therapy goes after the cause of the condition and attempts to fix it.”

GeneTx entered into a worldwide license agreement with The Texas A&M University System and a research collaboration agreement with Texas A&M AgriLife Research, under which GeneTx hopes to further develop and commercialize this novel antisense oligonucleotide as a targeted therapy for patients with the disorder.

“The FDA’s orphan drug designation for GTX-101 is an important next step in bringing effective treatments to individuals with Angelman syndrome,” said Paula Evans, GeneTx chief executive officer. “Activation of the normally silent paternal UBE3A gene has the potential to mitigate many of the disorder’s debilitating symptoms.”

The Orphan Drug Act became law in 1983. Fewer than 5,000 applicants have received this special designation, according to the FDA website. Rare conditions are often described as orphan diseases or disorders when there are few or no treatment options. There are about 7,000 known orphan diseases in the United States.

The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases, or disorders that affect fewer than 200,000 people in the United States.

The designation allows the sponsor of the drug to be eligible for various incentives, including a seven-year period of U.S. marketing exclusivity upon regulatory approval of the drug, as well as tax credits for clinical research costs, annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

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