Allergan plc, a leading global pharmaceutical company, and its partner, Editas Medicine, Inc. have been given the green light for a clinical trial designed to treat patients with severe blood disorders (hemoglobinopathies). As reported recently in a CheckOrphan article, this will be the first time the gene editing technology will edit DNA within the human body (in vivo).
The original plan was to file an application allowing the two companies to test the new product in vivo by late 2017. However, a manufacturing glitch set the tests back a year.
This delay was followed by a patent challenge that was countered successfully by Editas. The concern was centered upon the potential of CRISPR to make “off-target” cuts on healthy genes. Eventually, Editas was able to prove to the regulator that its product was safe and ready to be tested on humans.
The Phase 1/2 trial, named Brilliance, will study the tolerability, efficacy, and safety of a CRISPR-based genome editing medicine called AGN-151587. It is being developed to treat Leber congenital amaurosis 10 (LCA10) which is caused by abnormalities (mutations) in the CEP290 gene that result in blindness.
Eighteen patients with LCA10 will receive one of three different dose levels of the drug. The patients will be injected with one dose of AGN-151587 that will be carried by a human-made virus into the photoreceptor cells in the retina. The first patient dosing is expected to begin the second half of 2019. Additional information can be found here: NCT#03872479
CRISPR vs. Gene Replacement Therapy
Both therapies have certain advantages. CRISPR is able to deliver large genes that because of their size cannot be transported to retinal cells by the human-made viruses.
Also, under certain circumstances, it may not be necessary to replace an entire gene. Again CRISPR is the better choice due to its ability to either shut down or repair the errant gene rather than replace the gene entirely. This is often the choice when treating retinitis pigmentosa.
Scientists appear to be making progress in correcting the troublesome off-target effects. Therefore, it is entirely possible that CRISPR gene therapy will be at work in clinics in the near future.
Patient Worthy will keep you updated on the latest developments in the exciting new world of CRISPR.