RARE Daily

Astellas Takes $532 Million Charge Over Delay of Gene Therapy for XLMTM

April 29, 2021

Rare Daily Staff

 Astellas Pharma said, as a result of a clinical hold the U.S. Food and Drug Administration placed on its experimental gene therapy for the rare neuromuscular condition X-linked myotubular myopathy in June 2020 that was eventually lifted in December, it booked a $532 million (¥58.8 billion) impairment loss in the fourth quarter of the fiscal year ended March 31, 2021.

That charge has caused a difference between the financial forecasts, which were reported on October 30, 2020, and the actual results for the fiscal year 2020.

In December 2020, Astellas and its Astellas Gene Therapies (formerly Audentes Therapeutics) was notified that the FDA lifted the clinical hold for the ASPIRO clinical trial evaluating investigational gene therapy AT132 in patients with X-linked myotubular myopathy (XLMTM).

Audentes had already halted further dosing of patients enrolled in the ASPIRO trial when it reported at the end of June that two patients enrolled in the study had died. The ASPIRO trial was put on formal clinical hold with Audentes continuing to monitor enrolled patients and assessing the impact of the deaths on potential regulatory filing timelines. A third patient died in August and it was found that all three patients demonstrated evidence of pre-existing hepatobiliary disease.

The company said there is no change to its plan to continue development of the gene therapy. It said it will conduct future discussions with regulators on the path forward toward registrational filings for AT132.

X-linked myotubular myopathy (XLMTM) is a serious, life-threatening disease that is characterized by extreme muscle weakness, respiratory failure and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life. For those patients who survive past infancy, there is an estimated additional 25 percent mortality by the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,000 newborn males.

XLMTM places a substantial burden of care on patients, families, and the healthcare system, including high rates of healthcare utilization, hospitalization, and surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

AT132 is an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM. AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration.

AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the FDA, and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency.


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