PTC Therapeutics is delaying by at least three months the submission of an investigational new drug application requesting that the gene therapy candidate GT-AS enter clinical trials for Angelman syndrome.
The delay is a consequence of the COVID-19 pandemic, which has affected many preclinical studies and activities needed for the submission. Updates on timing will be given in the coming months, as the effects of this pandemic are better known, PTC said in a quarterly report.
PTC also announced delays in its gene therapy program for Friedreich’s ataxia and in the opening of a manufacturing facility in New Jersey, which is now expected to begin producing clinical material early next year.
Angelman syndrome is a rare neurologic disorder caused by the loss or dysfunction of the maternal copy of the UBE3A gene, which is central to producing the ubiquitin protein ligase E3A in neurons of the central nervous system.
This is because the UBE3A gene inherited from the father is shut down in select areas of the brain, in a natural process called genomic imprinting. When the maternal gene also is lost, these regions have little to no ubiquitin protein ligase E3A.
GT-AS, formerly known as AGIL-AS, is a gene therapy candidate designed to deliver a working version of the UBE3A gene to nerve cells in the brain and spinal cord of patients, thereby increasing the production of ubiquitin protein ligase E3A and countering the neurological defects caused by its deficiency.
The gene is delivered using an adeno-associated virus (AAV), a common and naturally occurring virus modified to be harmless and cause no infection.
Studies in animal models of Angelman have demonstrated that GT-AS effectively targets nerve cells in the brain, increases levels of ubiquitin protein ligase E3A, and eases the learning and memory deficits seen in these animals. Notably, benefits were seen in adult mice, indicating that the therapy may be effective in older Angelman patients.
PTC entered an agreement with Aldevron in November for the manufacturing of the DNA vectors for the company’s gene therapies. These vectors are small circular pieces of DNA (plasmids) that contain the functional gene — the UBE3A gene in the case of Angelman — needed to ease disease symptoms.
Aldevron will produce high-quality DNA plasmids that comply with good manufacturing practices (GMP), a set of guidelines that ensure a product is consistently made according to quality standards. This is a necessary step for regulatory agencies to allow a medicine to be tested in people.
While the company is expecting delay of at least three months in the initiation of clinical studies for GT-AS, PTC “cannot be certain that the pandemic will not cause us to experience further delays to the timelines … or other negative additional impacts,” the company wrote in the report.
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