Editas EVP and Chief Medical Officer Dr. Lisa Michaels/Editas Medicine.
The positive clinical data announced by Editas Medicine on Wednesday may represent the second-ever results from CRISPR gene editing inside the human body, but it is certainly not second-best to patients suffering from a form of inherited blindness called Leber congenital amaurosis type 10 (LCA10).
The milestone—still significant in that the editing took place in a different part of the body—followed that of Intellia Therapeutics, which, along with partner Regeneron Pharmaceuticals, became the first company to accomplish the feat in June.
LCA10 is an early-onset retinal degenerative disease that leads to significant vision loss and blindness. Editas’ experimental therapy, EDIT-101, targets a disease-causing mutation in the CEP290 gene that causes degeneration in ocular photoreceptor cells, which are critical for normal vision. Editas aims to knock this gene out and ultimately restore normal protein expression and vision.
The initial data from the ongoing Phase I/II BRILLIANCE trial, presented at the International Symposium on Retinal Degeneration, was based on six adult patients, with five evaluable for efficacy. The results for two patients in the mid-dose cohort followed for up to six months showed efficacy signals suggesting productive editing and indicators for clinical benefit, including improvements in best-corrected visual acuity (BCVA), FST, and/or mobility navigation.
The therapy’s safety profile was the primary bright point as there were no serious adverse events or dose-limiting toxicities. For Editas EVP and Chief Medical Officer Lisa Michaels, M.D., this is of paramount importance.
“The first and foremost conclusion on this is that we’ve been able to demonstrate, at least to date, that … CRISPR/Cas9 editing to the back of the eye is so far safe, and that was not known when we first started the study,” she told BioSpace.
Michaels, a pediatrician, pointed to the significance of moving into pediatric trials, which Editas received approval to begin enrolling in June based on early positive safety data.
“Being able to move into pediatric patients is very important because we’d like to get into patients while they still have more functioning photoreceptors and their brains are able to actually change,” she explained.
While the participants’ vision changes weren’t earth-shattering, Michaels said this was never the goal, at least in adult patients who often have very few photoreceptors remaining.
“How do you define meaningfulness?” she asked. “These patients have vision that varies anywhere from just being able to perceive light to seeing the world through a narrow little tunnel that’s fuzzy. It’s little things that become very meaningful to the patient. They could be just as simple as being able to see letters on a computer screen. Another one is the ability to maneuver through their bedroom at dusk and not run into the furniture. These are things that we are recording because they are meaningful to patients.”
Michaels shared that one patient is participating in the trial in the hopes of being able to see her grandchild’s face. Another participant, a 10-year-old child, wants to be able to go trick-or-treating without his mother having to lead him up to every door. “These are things that really impact people’s lives,” she said.
As it pertains to the surrogate measurements relating to eyesight, Michaels said, “What we’re seeing definitely in the first patient is a clearly defined improvement in her vision that’s reproducible at more than one moment, and in more than one measurement.”
While improvement was not noted in the low-dose cohort, Michaels said that Editas expected to see better outcomes in the high-dose cohort. The three-month mark was chosen for a first efficacy assessment because optimal editing and healing are believed to have occured during this period. Investigators will continue the patients at three-month intervals.
“I am encouraged by these initial results, which indicate this investigational gene-editing treatment has been well-tolerated in this trial’s participants thus far and may also help improve sight for people with mutations in the CEP290 gene. Being able to edit genes inside the human body is incredibly profound, and I hope to be able to offer my LCA patients new treatment options involving gene editing in the future,” said Mark Pennesi, M.D., Ph.D., professor of molecular and medical genetics; Kenneth C. Swan Endowed professor of ophthalmology; Paul H. Casey, ophthalmic genetics division chief, Casey Eye Institute, Oregon Health & Science University, and the BRILLIANCE principal investigator who presented the data.
Editas has already begun treating adult patients in the high-dose cohort. Michaels anticipates early data from this set in spring 2022 and the first pediatric data by the middle of the year.
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