First Patient Dosed in FORTIS Trial of AT845 for LOPD

The first patient has been dosed in the FORTIS Phase 1/2 trial of AT845, a single-dose gene therapy for adults with late-onset Pompe disease (LOPD).

AT845 is designed to deliver a healthy copy of the gene that encodes the enzyme acid alpha-glucosidase (GAA) directly to muscle cells. People with Pompe lack functional GAA, leading to the toxic accumulation of the sugar molecule glycogen in cells, most notably muscle cells.

FORTIS (NCT04174105), which is expected to enroll eight participants, will be conducted at eight sites across the U.S. and in Germany and the U.K. The first patient was dosed at one of the three U.S. sites now recruiting. More information on locations and contacts can be found here.

The trial is being conducted by Astellas Gene Therapies, the result of the acquisition of Audentes Therapeutics by Astellas Pharma. 

It will evaluate the safety and efficacy of AT845, given via intravenous (IV, into-the-vein) delivery, to LOPD patients ages 18 to 80. The eligible participants were treated for at least two years with Lumizyme (alglucosidase alfa, marketed as Myozyme in Europe), a GAA replacement therapy and the only Pompe treatment currently approved by the U.S. Food and Drug Administration.

“The only approved treatment for LOPD is to replace the enzyme through chronic, repeated injections, and lack of other therapeutic options represents a significant unmet need for these patients,” Nate Bachtell, MD, vice president of clinical development at Astellas Gene Therapies, said in a short video posted on Twitter.

In contrast, AT845 is given as a single dose. Participants in the FORTIS study will receive one IV infusion of either a lower or higher dose of AT845, followed by a 48-week (nearly one year) observation period and a five-year follow-up.

The trial’s primary outcomes are the safety and tolerability of AT845, as well as the change in GAA protein expression levels and activity from the study’s start to 12 weeks (about three months) post-treatment. 

“We’re grateful for the courageous Pompe patient community, the dedication of the study sites, and the years of commitment by the FORTIS study team, without whom this milestone wouldn’t be possible,” Bachtell added.

Astellas Gene Therapies is now a Gene Therapy Center of Excellence — created following the Astellas acquisition. It aims to advance the development of gene therapies for rare neuromuscular diseases, including Pompe and muscular dystrophy.

“The field of gene therapy has made significant strides to date, and we believe the future holds even greater opportunity to bring new treatments to a wide range of diseases for patients in need,” Kenji Yasukawa, PhD, Astellas’ president and CEO, said in a press release that had announced the company’s new divisions.

Astellas Gene Therapies, led by Ed Conner, MD, the site lead and division head of gene therapy medical & development, is charged with bringing the company’s gene therapy programs to clinical investigation.

“As we come together now as Astellas Gene Therapies, we are excited about the potential to leverage new resources that will further accelerate our pipeline while expanding our research and offerings to address the needs of larger patient populations on a global scale,” Conner said.