What’s Going on with Gene Therapy?

Recent Gene Therapy News

On August 20, 2020 Audentes Therapeutics, which was taken over by Astellas (ALPMY) for over $3 billion, announced that a third patient has passed away in a clinical trial evaluating its gene therapy product AT132 for the treatment of the life-threatening neuromuscular X-linked Myotubular Myopathy (XLMTM).

The neuromuscular disease is characterized by extreme muscle weakness, respiratory failure and early death. Preliminary findings indicate that the immediate cause of death was gastrointestinal bleeding.

A High Dose

This patient was one of three patients who received AT132 at a high dose and who demonstrated signs of liver dysfunction within 3 to 4 weeks after dosing. All three patients demonstrated evidence of pre-existing hepatobiliary disease. 

It is important to note that more than 50% of patients enrolled in the ASPIRO trial demonstrated evidence of pre-existing hepatobiliary disease but progressive liver dysfunction did not occur in the patients who took the lower AT132 dose.  

To date 23 ASPIRO patients have received AT132: six at the small dose and 17 at the high dose. Although the ASPIRO study is currently on clinical hold there are no other patients in the study who are currently experiencing similar liver dysfunction.

Audentes scientists and investigators of the ASPIRO trial, and independent Data Monitoring Committee, are currently closely monitoring all the enrolled patients in the study. Audentes is also investigating the reasons behind the three patients who developed progressive liver dysfunction.

The FDA put the study on hold.

Prohost Observations 

Three children with a rare neuromuscular disease have died after receiving a high dose of gene therapy in clinical trials conducted by Audentes Therapeutics. All three children were suffering liver problems. 

AT132 is designed to treat X-linked myotubular myopathy, a deadly disease caused by a single gene mutation.

Gene therapy has tremendously improved in the past 20 years regarding the safety and efficacy of the gene therapy approach. Before the advancement the worst problem was the failure in delivering the genetic material into the cells. The most important advancement has occurred in adeno-associated vectors which opened the clicnic door to gene therapy. Two gene therapy products have been approved and marketed. They demonstrated durable responses, bringing cures to intractable hereditary and acquired life-threatening genetic diseases.

Audentes used a higher dose in order to improve the durable positive results in neuromuscular diseases.  

Exaggerated Reaction Against Gene Therapy Firms

It is important for investors to pay attention to the exaggerated market reaction not only against Audentes or Astellas but against many other gene therapy firms who are carefully using their gene therapy. Investors put pressure on companies who contributed to the improvement of adeno-associated viral vectors.  One of the victims of the unwarranted selloff is Regenxbio (RGNX), which announced successful mid-term clinical trials results in its gene therapy for several intractable and life-threatening diseases.

Unsavvy investors have also caused selloffs in gene-editing firms, ignoring the fact that gene editing is not a gene replacement therapy and that CRISPR gene-editing technology, and Artificial intelligence (AI), are the future of treatment for most hereditary, acquired intractable and life-threatening diseases.

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Where is the Prohost Letter?

We apologize for its lateness and have been updating it based on many changes that are currently occurring due to the re-evaluation of many treatments. In addition to shuffling the Prohost Portfolio, we are including the two firms we promised and maybe more. 

To read more about these firms please use the search engine at our website.

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