Life Science Today 001 - Gene Therapy Deaths, FDA Guidelines, and CRISPR Tech
Originally Published as The Niche Podcast
Introduction
Welcome to the The Niche Podcast – Your weekly 5-minute rundown of the biotech, clinical research, and applied science industries. I’m your host, Dr. Noah Goodson. Today on The Niche we will be discussing two deaths in a gene therapy trial, new COVID-19 vaccine guidelines from the FDA, and recent developments in CRISPR-Cas gene editing technologies.
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Moving Forward after Two Deaths in Gene Therapy Trial of Myotubular Myopathy
Drs. James Wilson and Terry Flotte put out a brief report last week after two children enrolled in a phase one trial for X-linked Myotubular Myopathy passed away. X-linked Myotubular Myopathy typically causes individuals to experience a low quality of life and childhood mortality is the most common outcome of this debilitating genetic disorder.
A novel gene therapy had proven safe and effective in mice and non-human primates. However, the three patients given the highest dose of the AAV8 delivered gene therapy developed a severe hepatotoxic response, though the details are not well understood at this time. This immune-mediated response from the liver resulted in two of individuals passing away. Notably, patients with the “normal” AAV dose did not experience these serious adverse events. The trial is currently stopped. Whether or not they will be able to proceed after this will likely depend partially on the success of the normal dose patients as well as identification of the cause of death.
The delivery of pricy rare-disease gene therapies has continued to fuel the flow of capital from top Pharma players as well as VC backed ventures into the field. The FDA’s approval of the $2.125 million/dose gene therapy Zolgensma last year has kept hope around these mega-cost treatments alive. Despite setbacks due to COVID-19 across the research space, it is likely that the failure of new unicorns in the tech space and excess capital across the board will result in continued investment in various gene therapy methods and rare-disease single-gene targets. However, the recent deaths highlight the catastrophic consequences and massive challenges that face development of these therapies, even when robust pre-clinical data exists.
The study in question was sponsored by Audentes Therapeutics, which is currently owned by the Japanese multinational company Astellas Pharma whose shares have remained relatively stable around $16.50.
FDA COVID-19 guidelines – Released June 30
On June 30th the FDA released new regulations for all COVID-19 related vaccines. This report does not represent the final determination of what the FDA will want for approval. However, a critical guideline from the report was the requirement for 50% efficacy for any approved vaccine. In this context, efficacy may include decreased symptoms, severity, and duration, as well as the more obvious prevention.
Some experts consider 50% too high, while others suggest it may be too low. For comparison, the annual flu vaccine is usually 40-60% effective. In general, the 50% guideline likely indicates that FDA is trying to balance the need for a vaccine soon with desire for it to be reasonable effective. Keep in mind that a recent AP poll suggests that only 50% of Americans will get a vaccine if it is available meaning the public health challenges may outpace the scientific ones.
The current front-runner in the COVID vaccine race is Moderna whose stock went from around $20 a share in February to $58.57 at closing on Thursday.
Recent developments in CRISPR-Cas technologies
The cascade of novel CRISPR-related technologies continues this week. CRISPRs function as part of bacteria’s immune systems by creating targeted DNA cuts. Like all things with evolution, a good defense often leads to new methods of offense. A paper out July 3rd in Science by Alexander Meeske and colleagues demonstrates a novel method of viral offense against Cas13. They discovered a listeria phage virus that produces a protein AcrVIA1 which inactivates the function of the CRISPR protein Cas13. For the virus, this means it can survive the defense system and successfully replicate. For scientists, coopting proteins like AcrVIA1 may provide a means to activate and then de-activate a CRISPR system. This can theoretically lead to more temporally precise gene-editing methodologies down the road. Imagine being able to precisely edit a specific sequence of DNA and then turn off that machinery forever so that you don’t have continuous editing. There are extensive possibilities, given enough biotechnical refinement. Closing Credits
Thanks for joining me on The Niche Podcast. Our goal is to keep you informed so you can engage your colleagues. Join us weekly for a 5-minute summary of top news in the biotech, clinical trials, and applied science industries. You can find us on your favorite podcast app . Like, comment, subscribe, and most of all share with your friends in the industry. Once again, I’m Dr. Noah Goodson, I’ll see you next week.
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Story References
https://www.liebertpub.com/doi/10.1089/hum.2020.182
https://www.fda.gov/media/139638/download
https://apnews.com/dacdc8bc428dd4df6511bfa259cfec44
https://doi.org/10.1126/science.abb6151
Music by Luke Goodson
https://soundcloud.com/lukegoodson