FDA guidance emphasizes at least two orthogonal methods for off-target analysis.

Live Stream: https://www.youtube.com/watch?v=M90IjjxOdQg&ab_channel=U.S.FoodandDrugAdministration

•Biased vs Unbiased Techniques
•Biased: Focus on predicted off-target sites.
•Unbiased: Genome-wide search for off-targets.
•Combined use is likely required by the FDA.

•Complementary Approaches
•Improve confidence and reproducibility.
•Essential for robust study findings.
 

https://www.nytimes.com/2023/10/31/health/sickle-cell-fda-cure-crispr.html

Panel Says That Innovative Sickle Cell Cure Is Safe Enough for Patients

The decision by an advisory committee may lead to Food and Drug Administration approval of the first treatment for humans that uses the CRISPR gene-editing system.

"But there is a concern that CRISPR could inadvertently snip a piece of DNA in the wrong part of a patient’s genome. That might disrupt a gene and cause a blood cancer.

No such issues have turned up in the clinical trials, but the Vertex trial involved only 44 patients, and just 30 have been followed for at least 16 months. The company did extensive comparisons of patients’ DNA with that of people in large databases asking how likely such CRISPR misfires could be.

Vertex said it plans to follow clinical trial patients for 15 years. The company’s data were sufficiently reassuring that the expert committee said on Tuesday they saw no reason to hold the treatment back.

There can always be additional studies, noted committee member Alexis Komor, a professor of chemistry and biochemistry at the University of California, San Diego. But, she said, that would be “expecting perfection at the expense of progress.”

Dr. Joseph Wu of Stanford added, “We all agree that the benefits outweigh the risks. These patients are quite sick and this is a good therapy.”

Scot Wolfe of the University of Massachusetts Chan Medical School said, “We want to be careful not to let the perfect be the enemy of the good.”

“There is a huge unmet need,” he added.