Astellas Unveils Breakthrough Results of Pompe Gene Therapy Trial: A Potential Life-Changing Treatment

At the 19th Annual WORLDSymposium 2023, Astellas presented promising preliminary safety and efficacy data from their Phase I/II FORTIS trial of AT845 in late-onset Pompe disease (LOPD), a significant milestone after overcoming a clinical hold. The findings are a significant step forward in understanding this rare and debilitating disorder.

Astellas is at the forefront of a revolutionary new treatment for patients with LOPD: AT845, a one-time gene therapy that could replace the twice-monthly infusions of enzyme replacement therapy (ERT) currently used to manage Pompe disease. This groundbreaking approach could potentially offer a life-changing solution to those living with the condition.

On September 15, 2022, four brave participants took part in a groundbreaking medical trial involving a one-time intravenous infusion of AT845. Two patients received a 3×1013 vg/kg dose of the medicine, while the other two received a more concentrated 6×1013 vg/kg dose. This courageous act of participation could potentially benefit numerous individuals in the future.

At the data cut-off, three of the four participants had successfully weaned off ERT, showing sustained improvement in their functional endpoints, such as forced vital capacity and 6-minute walk test, over the course of 19, 44 and 51 weeks respectively. This is an encouraging sign of stability and progress!

As Wednesday’s presentation approaches, Richard Wilson, Senior Vice President and Primary Focus Lead for Genetic Regulation at Astellas, is emphasizing the importance of patient-reported fatigue outcomes as a key data point.

We are thrilled to see the positive results of the fatigue score, a key marker of quality of life, coming through! It’s an exciting time and we can’t wait to see what’s next.

The first participant in the low-dose cohort of a clinical trial was unable to come off enzyme replacement therapy (ERT), prompting a move to the higher-dose level, according to Ha Tran, M.D., executive medical director at Astellas. This unexpected turn of events represents an important development for the study and its participants.

Astellas has rigorously monitored the safety of its trial participants for up to 72 weeks, taking a staggered approach to ensure the utmost care and attention to detail.

Pompe disease is an incredibly serious metabolic disorder that can have devastating effects on the body. It is caused by a mutation in the GAA gene, which is responsible for creating an enzyme called acid alpha-glucosidase (GAA). GAA’s job is to break down glycogen, and when it is mutated, the body cannot process glycogen correctly, leading to muscle and nerve cell damage. It is an autosomal recessive disorder, meaning that it is passed on from both parents and can be inherited.

Glycogen serves as an energy reservoir in the body, delivering a powerful punch of energy to fuel muscle movements when needed. It is an essential source of energy for the body, allowing it to quickly and efficiently access energy when needed.

The revolutionary AAV-GAAAT845 gene replacement therapy is paving the way for a bright future for adult patients living with Pompe disease. Using an experimental adeno-associated virus, this treatment delivers a functional copy of the GAA gene directly into the muscle cells, offering an exciting opportunity to restore the body’s ability to break down and store glycogen.

Therapy for those living with LOPD has taken a revolutionary turn, according to Wilson. The new approach to delivering treatment is an innovative one, setting it apart from traditional methods.

By delivering a gene directly to a patient’s muscles, we are able to provide them with the enzyme they need without having to rely on the diffusion of an intravenous infusion. This method of treatment is more effective than enzyme replacement therapy (ERT), as it allows for the enzyme to be produced in situ, providing the patient with the necessary benefits.

ERT may not be a permanent solution, as its efficacy could diminish over time and it has the potential to cause immunogenic events.

Up and Running

The FDA halted the FORTIS study in June 2022 when one participant experienced peripheral sensory neuropathy. However, in January 2023, Astellas managed to satisfy the FDA’s rigorous benefit-risk threshold, and the clinical hold was lifted.

The company is now expanding their study by enrolling two more participants, in order to gain a deeper understanding of the safety and early efficacy signals. This will help them to further refine their research and get one step closer to achieving their goal.

Safety is a top priority for Ha. They take great care to ensure that all of their procedures are safe and up-to-date with the latest industry standards. They understand the importance of keeping their staff and clients safe, and are constantly working to make sure that their standards are maintained.

In order to ensure the safety of patients who may be at risk of developing peripheral neuropathy, we are implementing stricter inclusion criteria to our program.

Astellas has found no indication of any issue with the AVV gene therapy, according to Dr. Wilson. He reassured that everything appears to be running smoothly and there is nothing to be concerned about.

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