FDA Grants ASC618 Fast Track Designation for Hemophilia A

The gene therapy ASC618 has been granted a Fast Track Designation by the FDA and a positive opinion by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products as a potential treatment for patients with hemophilia A, according to a statement from ASC Therapeutics, the developer of the AAV8-based gene therapy.

The FDA approved an Investigational New Drug (IND) for ASC618 in mid-2021, and a phase 1/2 study is currently exploring the therapy for patients with hemophilia A (NCT04676048). The study investigators plan to recruit 12 participants aged 18 and older with severe or moderately severe hemophilia A (FVIII activity ≤ 2 IU/dL) to examine ASC618, which is administered by a single IV infusion. The primary outcome measures for the study are safety, tolerability, and preliminary efficacy and the principal investigator is Steven Pipe, MD, PhD.

“ASC618 design provides a novel perspective to the field of hemophilia gene therapy," Pipe, professor of pediatrics and pathology and pediatric medical director of the hemophilia and coagulation disorders program at the University of Michigan, said when the IND was granted. "For the first time we will be able to investigate in a clinical setting the relevance of a novel bioengineered construct that has been proven in pre-clinical studies to significantly improve the biosynthesis, protein folding and secretion of factor VIII.”

The Fast Track Designation is meant to facilitate and expedite the development of treatments for serious conditions that fill an unmet need. With the hemophilia A designation, ASC Therapeutics will benefit from more frequent interaction with the FDA. Additionally, if clinical studies are successful, the company will be eligible for an accelerated approval, priority review, and the ability to submit a rolling biologic license application. In addition to this designation, the company has also received an Orphan Drug Designation in 2020 for ASC618.

“These regulatory milestones culminate years of hard work, dedication, and collaborative efforts by our functional teams," Oscar Segurado, MD, PhD, Chief Medical Officer at ASC Therapeutics, said in a statement. "Preclinical studies have shown that ASC618 has the potential to reduce therapeutic dosing and increase durability of hemophilia A gene therapy with a novel bioengineered construct that can improve biosynthesis, protein folding, and secretion of factor VIII.”

READ MORE: Gene Therapy Potential in Hemophilia: Steven W. Pipe, MD

The AAV8-based gene therapy incorporates a liver-specific promoter and encodes for a codon-optimized bioengineered, B domain-deleted FVIII variant combined with a minimal synthetic hybrid liver promoter. Preclinical studies on cell lines and murine models conducted prior to the IND showed a 10-fold increase in biosynthesis secretion of FVIII compared with native human FVIII constructs, according to the company.

“We are very pleased with the FDA's and EMA’s regulatory decisions regarding ASC618," Ruhong Jiang, PhD, Chief Executive Officer at ASC Therapeutics, said in a statement. "This brings us one step closer for providing a truly novel therapeutic approach for hemophilia A, providing potentially a functional cure for patients who currently require life-long care.”

The ASC Therapeutics pipeline is focused exclusively on blood disorders. In addition to cell and gene therapies, the company is also exploring gene editing approaches using TARGATT, a proprietary integrase-driven technology. The lead agent in their pipeline is a placenta-derived cell therapy called ASC930 that is focused on graft-vs-host disease. It is currently undergoing phase 2b studies (NCT04883918).