Audentes Therapeutics Plans to File Investigational New Drug Application for Potential Pompe Disease Gene Therapy This Year

José Lopes, PhD avatar

by José Lopes, PhD |

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Audentes Therapeutics plans to submit an investigational new drug (IND) application for its Pompe disease gene therapy AT845 this year.

In a recent update, Audentes, a biotech company, discussed its portfolio of investigational gene therapies for rare diseases.

“2018 was an outstanding year for Audentes,” Matthew R. Patterson, Audentes’ chairman and CEO, said in a press release. “In our Pompe disease program, we are encouraged by the progress of our ongoing preclinical studies and are planning to file an IND for AT845 in the third quarter of 2019.”

AT845 is intended to provide long-term production of an enzyme called acid alpha-glucosidase (GAA), required to break down glycogen into glucose, which is used by cells to produce energy. Pompe disease is caused by mutations in the GAA gene, which impair production or activity of the enzyme.

Audentes’ gene therapy contains modified, harmless viral vectors carrying the GAA gene, which is expected to raise GAA enzyme levels, subsequently easing Pompe disease’s symptoms.

AT845 has shown encouraging results in multiple studies, according to Audentes. In GAA-deficient mice, AT845 led to significant increases in enzyme activity in heart and skeletal muscle. This resulted in improved diaphragm contractile strength, decreased cardiac glycogen and left ventricular mass, and improved ejection fraction — a measurement of how much blood the left ventricle pumps out with each contraction.

An additional study in a mouse model of Pompe disease found improvements in diaphragm contractile and cardiac function with both a single systemic injection of AT845 and bi-monthly injections of recombinant human GAA over three months. In turn, breathing frequency and expiratory time only improved with AT845, while glycogen accumulation was significantly increased in untreated and human GAA-treated animals, but not in those receiving AT845.

Besides Pompe disease, Audentes is also developing gene therapy candidates for X-linked myotubular myopathy and Crigler-Najjar syndrome.

In X-linked myotubular myopathy, Patterson mentioned positive results of an ongoing Phase 1/2 trial (NCT03199469, still recruiting participants), which include meaningful improvements in neuromuscular and respiratory function, as well as the promising clinical profile of AT132.

Audentes is also developing AT342 for patients with Crigler-Najjar syndrome. The therapy was granted rare pediatric disease and fast track designations by the U.S. Food and Drug Administration.

Patterson said that Audentes will also be developing AT720 “to treat a large neuromuscular disease with significant unmet medical need.” Details on its therapeutic target and program overview are expected in the second quarter of the year.

Audentes announced a strengthened balance sheet after two follow-on financings that resulted in aggregate net proceeds of approximately $380 million. As of Sept. 30, 2018, Audentes had cash, cash equivalents and short-term investments of approximately $450 million.

The company’s clinical success, Patterson said, “is supported by a strong balance sheet,” anticipated to fund operations into 2021.  “With over two years of cash runway, we are well-positioned to make meaningful progress toward our goal of providing transformative therapies to patients living with devastating rare diseases,” he said.

Patterson provided a corporate update at the 37th Annual J.P. Morgan Healthcare Conference, on Jan. 8. A replay of the webcast will be available here for approximately 30 days beginning Jan. 10.