BioPharma

Astellas’ Audentes Therapeutics discloses third patient death in gene therapy trial

The clinical trial had already been placed on hold in connection with the two prior patient deaths, which were linked to the higher dose of 300 trillion viral vectors per kilogram, while no deaths have been reported among those receiving the lower dose of 100 trillion vectors.

dna, genomics

A third patient in the trial of a gene therapy for treating a rare and life-threatening neuromuscular disease that has already been placed on clinical hold has died, the company developing the therapy said Friday.

Audentes Therapeutics – which Japanese drugmaker Astellas acquired in December 2019 for $3 billion – disclosed that the immediate cause of the death of a third patient in its Phase I/II ASPIRO trial of AT132 in X-linked myotubular myopathy, or XLMTM, was gastrointestinal bleeding.

Shares of Astellas fell slightly on the over-the-counter market, where they trade in the U.S. The Tokyo-based company’s shares principally trade on the Tokyo Stock Exchange.

The patient was one of three in the trial who had received the gene therapy at a dose of 300 trillion viral vectors per kilogram of body weight and had begun to demonstrate signs of liver dysfunction within three to four weeks after receiving the dose. The trial is enrolling boys up to the age of 5.

All three of the patients demonstrated signs of pre-existing hepatobiliary disease, a term referring to disease of the liver and bile ducts or gall bladder. However, more than half of the patients enrolled into the study so far showed signs of such disease, though the gene therapy has not been associated with similar complications when administered at the 100 trillion vector per kilogram dose. To date, 23 patients have received AT132, including six at 100 trillion vectors and 17 at 300 trillion vectors.

Audentes had previously said in late June that a patient in ASPIRO had died of sepsis, a month after another patient had also died.

The announcement marks the second significant setback this week for gene therapies. On Wednesday, San Rafael, California-based BioMarin said the Food and Drug Administration had delivered a complete response letter for its application to secure approval for valoctocogene roxaparvovec, a gene therapy for hemophilia A. The news came as a surprise to many, given that the therapy was widely expected to win approval, and the company itself said the issues raised in the CRL had not been raised previously.

Photo: iLexx, Getty Images

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