At the end of June, the National Hemophilia Foundation (NHF) released a warning to patients with hemophilia regarding AT132, an investigational gene therapy candidate. Developed by Audentes Therapeutics, AT132 uses adeno-associated virus (AAV) vectors. Additional therapies from Audentes Therapeutics, such as those for hemophilia, also use AAV vectors. Unfortunately, says the NHF, two patients with X-linked myotubular myopathy (XLMTM) in the ASPIRO trial for AT132 died. This is not to say that gene therapy is unsafe; it is, in many ways, effective and should still be studied. However, patients of any kind using AAV-related therapies should proceed with caution.
ASPIRO Trial & Associated Deaths
The ASPIRO trial, a multinational and open-label study on AT132, sought to understand the safety, tolerability, and efficacy of the gene therapy candidate in pediatric patients with XLMTM. After being treated intravenously, two patients died over the course of the study. According to Audentes, the most recent patient died of sepsis following progressive liver dysfunction and hyperbilirubinemia. Although only two patients have died, one additional patient experienced a severe adverse reaction (hepatobiliary disease).
For patients with hemophilia, the NHF released recommendations regarding the risk of gene therapy trials following this news.
X-linked myotubular myopathy (XLMTM) is a muscular condition which mainly affects skeletal muscles. Caused by MTM1 gene mutations, XLMTM almost only occurs in males. XLMTM symptoms are usually seen at birth and many patients only live until early to late childhood.
Symptoms and features of XLMTM include:
- Fragile bones and poor bone development
- Hip and knee deformities
- Difficulty feeding, walking, standing, or sitting
- Poor fine motor skill development
- Muscle weakness
- Severe breathing problems and difficulty breathing on their own
- Low muscle tone
- Poor or absent reflexes
- Facial and optic muscle weakness
- Liver disease
Learn more about XLMTM.