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Gene Therapy for Rare, Pediatric Condition Moves Closer to Reaching U.S. Patients

A collaboration between researchers from NCATSTherapeutics for Rare and Neglected Diseases (TRND) program and Agilis Biotherapeutics, Inc., of Cambridge, Massachusetts, has resulted in a gene therapy for the rare pediatric condition aromatic L-amino acid decarboxylase (AADC) deficiency moving closer to market years ahead of schedule. Following a recent meeting with the U.S. Food and Drug Administration (FDA), Agilis will begin the process of seeking final approval to treat U.S. patients with this life-threatening disorder (PDF - 67KB).

The AADC enzyme is necessary to produce important chemical messengers in the brain and other parts of the central nervous system. Children with AADC deficiency commonly experience severe developmental delays, weak muscle tone and involuntary movement of the limbs. There is no approved treatment for AADC deficiency, and patients with severe forms of the disorder usually die in the first decade of life.

The gene therapy, called AGIL-AADC, restores AADC enzyme production in the brain. Agilis licensed the gene therapy from National Taiwan University, where investigators had conducted clinical studies on patients with severe AADC deficiency. While these studies showed drastic and sustained improvements following a single dose of AGIL-AADC, the investigators lacked pre-clinical data required by the FDA. The small market for this ultra-rare disease and the need to conduct additional studies threatened to stall the project.

In 2016, through a cooperative research and development agreement, Agilis partnered with NCATS scientists in the TRND program, which is designed to speed the development of new treatments for diseases with significant unmet medical needs. TRND scientists supported the development of AGIL-AADC in several ways, including conducting pre-clinical safety studies and producing AGIL-AADC in a way that met FDA requirements.

In just over a year, these efforts led to a meeting with the FDA to review the pre-clinical, clinical and manufacturing data. In an unusual step, FDA reviewers determined that Agilis did not have to repeat clinical trials in the United States, clearing the path for the company to file a Biologics Licensing Application (BLA), which, if approved, would allow the company to market AGIL-AADC to patients.

“The successful partnership between the Agilis and TRND teams helped shorten the timeline by years for this potentially lifesaving therapy to reach patients,” said Nora Yang, Ph.D., director of portfolio management and strategic operations in NCATS’ Division of Pre-Clinical Innovation.

As Agilis prepares to file a BLA, the TRND and Agilis team is conducting an epidemiological study to better define the prevalence of AADC and identify patients who might gain access to this potentially lifesaving gene therapy.

AGIL-AADC is poised to be among the first FDA-approved gene therapies for treating a central nervous system disorder. Moreover, it would be the first therapy supported by the TRND program to receive marketing approval from the FDA and become available to patients.

“This significant regulatory milestone demonstrates how the TRND program plays a catalytic role in enabling and accelerating progress on rare disease therapies through public-private partnerships,” Yang said.

Posted September 2017

Last updated: 09-19-2017
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