BioPharma

Audentes – bought by Astellas for $3B – discloses new patient death, gene therapy trial hold

The company disclosed in a letter to the X-linked myotubular myopathy patient community that a second child in its Phase I/II study had died. A formal clinical hold has been placed on the trial.

The clinical trial of a gene therapy for a rare inherited disease that causes muscle weakness has been put on hold following the deaths of two patients.

Last week, Audentes Therapeutics – which Tokyo-based drugmaker acquired in December 2019 for $3 billion – sent a letter to members of the patient community disclosing that a patient in the Phase I/II trial of the gene therapy AT132 in X-linked myotubular myelopathy had died of sepsis. The death came a month after another patient had also died. The 24-patient trial is enrolling children up to the age of 5.

On Monday, shares of Astellas were down 2% on the Tokyo Stock Exchange when the market closed, but were mostly flat on the over-the-counter market, where they trade in the U.S.

In the letter, provided via email by a company spokesperson, the company said that the enrollment into the study had been halted prior to both patient deaths, after consultation with the study’s data monitoring committee, and the trial was subsequently placed under a formal clinical hold after the company consulted with the Food and Drug Administration.

Both of the patients who died were among three older patients who received AT132 at a dose of 300 trillion vectors per kilogram of body weight. The company said that dose level had been associated with serious liver toxicity, but that among six patients treated at the 100 trillion-vector dose, there had been no incidence of serious liver toxicity, even years after treatment, despite four of them having a history of liver disease.

The therapy is an adeno-associated viral vector gene therapy, which is designed to work by using reprogrammed viruses to “infect” cells with corrected genes. Most gene therapies on the market or in clinical development use viral vector technology. X-linked myotubular myopathy, or XLMTM, mainly affects males and is estimated to occur in 1-in-50,000 live births.

Audentes still has an additional gene therapy that it is preparing to enter into the clinic, AT845, for the lysosomal storage disorder Pompe disease. Another therapy in preparations for clinical development, AT702, for Duchenne muscular dystrophy, is designed to work by vectorized exon skipping.

Photo: XtockImages, Getty Images

Shares0
Shares0