Tahseen Mozaffar, MD, FAAN

“The biggest advantage here would be that, rather than being dependent on an exogenously delivered enzyme that has to be given every 2 weeks with a significant amount of infusion-related reaction, plus a time commitment—because the infusion takes about 4 hours—you would be in a situation where your body is producing its own enzyme, either in the liver or in the muscle.”

Pompe disease is a rare neuromuscular disorder affecting 1 person in every 40,000, with approximately 1 out of every 28,000 babies in the US born with the condition. Currently, the only available treatment is enzyme replacement therapy (ERT), which has risk of infusion-related reaction and requires biweekly administration.

 (Astellas Pharma), an investigational adeno-associated gene replacement therapy offers another approach, delivering a functional GAA gene to express acid alpha glucosidase directly into muscle cells. An ongoing study, the phase 1/2 FORTIS trial (NCT04174105), is evaluating the treatment in adults with late-onset Pompe disease, with positive interim safety data from 4 patients announced by the company in February.

Tahseen Mozaffar, MD, FAAN, director, UC Irvine-MDA ALS and Neuromuscular Center, director, Division of Neuromuscular Diseases, Neurology School of Medicine, and professor of neurology, pathology, and orthopaedic surgery, University of California, Irvine, spoke with 

 on this data, emphasizing the benefits it may offer patients with Pompe disease, with investigators anticipating the efficacy of AT845 to be higher than that of ERT. Mozaffar further discussed challenges and areas for future research in Pompe disease, noting the potential mRNA approach, which was used by Pfizer/BioNTech and Moderna for their respective COVID-19 vaccines.

Videos

On Rare Disease Day, the director of the Division of Neuromuscular Diseases at UC Irvine commented on the potential of AT845 for this patient population. [WATCH TIME: 3 minutes]

The Benefits of a New Therapy for Pompe Disease: Tahseen Mozaffar, MD, FAAN

“FORTIS is a muscle-directed approach, where the enzyme is going to be produced locally in the muscle, it will have steady levels, and hopefully, it will do a better job of clearing out glycogen and stabilizing the disease.”

 of AT845 in adults with late-onset Pompe disease (LOPD) were presented at the 18th Annual WORLDSymposium, February 7-11, 2022, in San Diego, California, by Astellas Pharma. The investigational adeno-associated gene replacement therapy delivers a functional 

 gene to express acid α glucosidase directly into muscle cells.

To better understand findings, we sat down with Tahseen Mozaffar, MD, FAAN, director, UC Irvine-MDA ALS and Neuromuscular Center, director, Division of Neuromuscular Diseases, Neurology School of Medicine, and professor of neurology, pathology, and orthopaedic surgery, University of California, Irvine. In conversation with 

, Mozaffar outlined the importance of AT845 as a treatment in that it offers an alternative to enzyme replacement therapy, which is currently the only approved therapy for treatment of Pompe disease and requires biweekly IV infusions.

Trial investigators have dosed 4 patients thus far in the FORTIS study, with the intention to enroll approximately 8 to 12 patients, Mozaffar said. In those that have been dosed, the treatment was “very well tolerated,” he added, noting that there were no major treatment-related adverse events or treatment-emergent adverse events. One patient did report abnormally high liver function tests, specifically the transaminases, but the patient responded to steroid therapy and levels were lowered, he said.

REFERENCE
1. Astellas announces positive safety data from the FORTIS study of AT845 in adults with late-onset Pompe disease. News release. February 7, 2022. Accessed February 8, 2022. https://www.biospace.com/article/releases/astellas-announces-positive-safety-data-from-the-fortis-study-of-at845-in-adults-with-late-onset-pompe-disease/

The director of the Division of Neuromuscular Diseases at UC Irvine discussed the positive data, noting that the treatment was “incredibly safe.” [WATCH TIME: 4 minutes]

Tahseen Mozaffar, MD, FAAN

Articles

The Benefits of a New Therapy for Pompe Disease: Tahseen Mozaffar, MD, FAAN

Interim FORTIS Study Safety Data for AT845 in Adults With Late-Onset Pompe Disease: Tahseen Mozaffar, MD, FAAN

Latest News