Potential Angelman’s Treatment, GTX-102, Named Orphan Drug and Rare Pediatric Disease Therapy by FDA

A potential treatment for Angelman syndrome, GTX-102, has been granted both orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration (FDA) to support and help speed its advancement.

The companies co-developing GTX-102 plan to file an investigational new drug application with the FDA in early 2020, requesting the start of clinical testing.

Angelman syndrome is a neurological disorder caused by the loss or malfunction of the maternal copy of the Ube3a gene in neurons found in specific regions of the brain. People inherit two copies of the Ube3a gene, one from their mother and one from their father, but only the mother’s gene is active in certain brain areas.

GTX-102, originally developed by GeneTx Biotherapeutics, is an antisense therapy that can silence gene expression by binding to the RNA molecule that regulates its expression. (Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.)

It is designed to target and inhibit the molecule that silences the paternal copy of the gene, called Ube3a antisense transcript (Ube3a-AS). Preclinical studies have shown that GTX-102 activates the paternal copy of the UBE3A gene in neurons (nerve cells) grown in the lab, and can ease certain disease symptoms in a mouse model of Angelman syndrome.

GeneTx Biotherapeutics entered into a partnership with Ultragenyx Pharmaceutical to develop GTX-102 in August 2019.

“Angelman syndrome is a devastating neurological condition with no treatment options that represents a very significant unmet medical need,” said Emil D. Kakkis, MD, PhD, chief executive officer and president of Ultragenyx, said in a press release. GTX-102 “is a novel and promising potential therapy specific to the disease mechanism in these patients,” Kakkis added.

“GeneTx was formed by the Foundation for Angelman Syndrome Therapeutics (FAST), the largest patient organization in the Angelman community. Donations to FAST, from family and friends, supported the preclinical research on this therapeutic strategy,” said Paula Evans, chief executive officer of GeneTx.

Orphan drug designation provides the developers of a therapy like GTX-102 benefits such as seven years of market exclusivity (if approved) and exemption from FDA application fees, tax credits for costs associated with clinical trials, an exemption to prescription drug user fees, and FDA assistance in designing clinical trials.

Rare pediatric disease designation is granted to product applications for diseases that affect fewer than 200,000 children in the U.S., ages 18 or younger.

With this designation, the companies might become eligible to receive FDA’s priority review vouchers, if the application meets specific criteria. The priority review voucher program was created as an incentive for companies to develop treatments for rare diseases that might not otherwise be profitable to develop, because these diseases affect relatively small numbers of people.

GTX-102 is GeneTx Biotherapeutic’s second antisense therapy candidate for Angelman syndrome. Its first, GTX-101, was designated an orphan drug by the FDA in April 2018.