Audentes’ rare disease gene therapy programme delayed after third patient death

Audentes Therapeutics has indefinitely delayed plans to seek regulatory approval for its rare disease gene therapy after the death of a third patient involved in a clinical trial of the drug.

This was the third death of a patient involved in the Audentes’ ASPIRO clinical trial, which is evaluating its AT132 gene therapy in patients with X-linked myotubular myopathy (XLTM), a rare neuromuscular disease.

XLTM mainly affects males and causes muscle weakness that ranges in severity from mild to life-threatening. In severe forms of the disease, the weakened muscle make breathing difficult and can lead to respiratory failure. The genetic disorder has a mortality rate of around 25% by the age of ten.

AT132 is an aden-associated virus (AAV) based gene therapy that is designed to deliver the MTM1 gene deficient in XLMTM. According to Audentes, preliminary findings show that the immediate cause of death of the third patient was gastrointestinal bleeding.

The patient ws one of three study participants who had received AT132 at a dose of 3x1014 vg/kg, the higher dose, who subsequently began to demonstrate signs of liver dysfunction within three to four weeks after initial dosing.

The three patients also demonstrated evidence of pre-existing hepatobiliary disease, although over half of the patients enrolled in the study also showed evidence of the same pre-existing conditions.

Audentes, which was bought by Japanese pharma company Astellas last year, was forced to put the ASPIRO trial on hold in June after disclosing the first two patient deaths.

“Audentes, together with the ASPIRO investigators and independent Data Monitoring Committee, continues to closely monitor all patients enrolled in the study. Additionally, Audentes’ investigation into why these three patients developed progressive liver dysfunction is ongoing,” the company said in a statement.

Although the study is currently on hold, Audentes maintained that there are no other patients involved in the trial that are known to be experiencing similar liver disfunction.

The company plans to provide further information on the ASPIRO programme based on both ongoing data collection and future regulatory status updates.