According to MedCity News, a third patient dosed with AT132 during the ASPIRO trial has died. The Phase 1/2 clinical trial tested the efficacy, safety, and tolerability of AT132 for patients with X-linked myotubular myopathy (XLMTM). Developed by Audentes Therapeutics, AT132 is an investigational gene therapy candidate.
Due to the number of deaths, the ASPIRO trial is currently on hold. However, it was previously enrolling male participants with XLMTM up to age 5. Prior to the trial shutting down, 23 patients received either 100 trillion vectors/kg or 300 trillion vectors/kg of AT132 based on weight.
So far, all three patients who died received 300 trillion vectors/kg. Within one month, the patients showed signs of liver dysfunction. While researchers believe they may have already had hepatobiliary disease, there is a chance that AT132 is related. After all, over 50% of enrollees show the same signs. However, the drug seems safer in smaller doses (100 trillion vectors).
It is unclear how or why the first patient died. However, the second death was linked to sepsis. The most recent death resulted from gastrointestinal bleeding.
XLMTM
According to the NIH, x-linked myotubular myopathy (XLMTM) is:
a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth.
Patients with XLMTM usually only survive into early childhood. This is because muscle weakness causes a variety of motor and breathing problems. In addition to difficulty standing, sitting, walking, or feeding, many infants are unable to breathe without assistance. As a result, pediatric patients often require mechanical ventilation. This ranges from continuous need to use only during certain times of the day, such as sleeping. Additional symptoms include:
- Scoliosis
- Poor bone development
- Fragile bones
- Joint pain and deformities
- Muscle weakness
- Absent reflexes
- Difficulty controlling eye movement
- Liver disease
- A large head with a narrow face
- A high palate
- Recurrent ear and respiratory infections
- Epilepsy and seizures
Learn more about XLMTM.
