UPDATED: Editas' gene-editing data has company touting prime time based on early vision improvement signals but questions remain

stage curtains
Editas’ study is being conducted to confirm safety and escalate dosing to where the editing may begin to show a strong effect in reversing the condition. (Getty Images)

Editas Medicine may have been first to enter the clinic with a gene-editing therapy, but it was beaten to the finish line by Intellia with first-in-human results in June.

But it’s not a competition. Or is it?

“Well, I’m mad at them for reporting data before me,” joked Editas’ Chief Medical Officer Lisa Michaels, M.D., in an interview with Fierce Biotech.

All jokes aside, CRISPR/Cas9 gene-editing biotech Editas now says it has proof-of-concept human data for vision loss therapy EDIT-101 to present today, Sept. 29, at the XIXth International Symposium on Retinal Degeneration in Nashville, Tennessee.

Editas published data on just two patients from the low-dose cohort of the phase 1/2 BRILLIANCE trial for retinal degenerative disorder Leber congenital amaurosis 10, or LCA10. Additional data from four patients who received a middle dose of EDIT-101 will also be presented.

RELATED: Intellia hits a 'home run' with gene-editing results, setting up entire field for a grand slam

Though the numbers are small, the biotech says it has confirmed safety—and its concept—in this group of patients and has enough data to report patients in that middle dose group are starting to see some signals that their vision may be improving.

But the market seemed to disagree that the data Editas dropped are enough to form a full opinion on whether the gene editing therapy will work or not. Editas' shares dropped 16% to $44 compared to $49 at open, as questions swirled about the safety data and whether patients saw meaningful improvement. 

LCA10 is a genetic disorder characterized by severe visual impairment that typically begins in infancy. Patients with this type of vision loss have difficulty seeing at night and extreme farsightedness.

EDIT-101 targets a disease-causing mutation in the CEP290 gene that causes degeneration in ocular photoreceptor cells that are critical for vision. The therapy removes the mutation to try to restore normal protein expression and photoreceptor function, with the ultimate goal being to restore vision.

Editas’ study is being conducted to confirm safety and escalate dosing to where the editing may begin to show a strong effect in reversing the condition.

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“We're starting to see data that supports that the editing technology is not only working but may be really beneficial for patients with blindness,” Michaels said.

Betting 10 bucks

Confirming safety in this trial is a huge milestone for Editas, according to Michaels. When the biotech entered the clinic with EDIT-101, it was breaking ground. But there were concerns about whether the treatment, which is delivered using an adeno-associated virus, might cause uncontrolled or unexplained inflammation or cause patients to lose the vision that they did have.

“When the study was first conceived, no one had ever done gene editing in the body and people were very concerned about the potential immune reactions that might occur with AAV-directed CRISPR/Cas9 therapy,” Michaels said.

After 15 months of follow-up, Editas has not seen any concerning safety signals in the first two patients. The adverse events that were reported were attributed to the surgical procedure to deliver the treatment. 

RELATED: AbbVie cuts Editas CRISPR pact it inherited from Allergan

With those data in hand, Editas looked to the mid-dose group to start seeing signals of efficacy.

“If you asked me to put 10 bucks on the table and make a bet that we would start to see some editing efficiency … this was the cohort where I was really hoping to see it,” Michaels said.

And that’s what Michaels believes they saw. The data are very preliminary, and one challenge of this type of CRISPR/Cas9 technology is that it’s delivered directly to the retina, so Michaels and her team can’t simply biopsy the material to check for evidence of editing. Instead, they look for so-called clinical biomarkers to determine effect, which for the sake of this study is a measure of best corrected visual acuity. Patients are tested to see whether they can perceive different levels of light and are put through a maze to measure their ability to maneuver in different light levels.

The early data have shown some trends toward improvement on these measures, Michaels said.

Specifically, two patients in the mid-dose group showed efficacy signals that suggest editing has occurred and that clinical benefits of improved mobility, light sensitivity, navigation and other measures have been detected.

One of those subjects showed improvement in best corrected visual acuity and had a "positive trend" towards improved retinal sensitivity in the eye that was treated. This patient also demonstrated an improvement in mobility at month six. 

The second patient had improvement in best corrected visual acuity at month three and "a notable improvement" in retinal sensitivity that was seen at 1.5 months and sustained at three months. 

RBC Capital Markets analyst Luca Issi noted that the improvement in the one patient noted by Editas was slim and fell short of what was seen with a competing therapy in development by ProQR Therapeutics. Issi also questioned one safety report of "mild anterior chamber inflammation," which could become an issue as Editas escalates dosing. 

Patients are being reassessed every three months and will be followed for three years to observe improvement over time. The data presented today are from patients who are at least three months out from treatment—which is the earliest Michaels and her team had expected to see evidence of editing. 

RELATED: The next generation of gene therapy for rare diseases forges ahead as developers weather hurdles

With this early dose-escalation evidence in hand, Editas can now move to a higher dose to test for better efficacy.

“With each consecutive dose level, we are predicting more editing,” Michaels said. “The fact that we've gotten this far and have the ability to move on to the next dose cohort is a big milestone for me.”

The biotech has also received FDA clearance to test EDIT-101 in children in an attempt to deliver treatment earlier in life when Michaels believes stronger vision restoration could be achieved.

Trick or treat

These milestones almost didn’t happen at all. Editas dosed the first patient with EDIT-101 early last year—just as the COVID-19 pandemic began to take hold. That first patient had trouble moving back and forth between home in Southern California and the test site in Oregon for treatment, which stalled the program. When Michaels joined the company in November, just as the second patient was dosed, she set to work getting the trial back on track. That work resulted in the publication of initial data from the BRILLIANCE study today.

RELATED: Editas bags $25M from Allergan as FDA signs off on human CRISPR trial

EDIT-101 was previously part of a $90 million pact with Allergan, but the partnership was ditched in August 2020 after the pharma was bought out by AbbVie, forcing Editas to go it alone. 

Editas’ data build on what Intellia did a few months earlier: proving the concept of CRISPR gene editing in humans. Intellia’s therapy targets the liver, while EDIT-101 is delivered to the eye, a key difference, but data for either concept represent a major advancement for the field as a whole.

“I'm very proud to see that Intellia and our program in combination actually can show the real potential of CRISPR editing technologies,” Michaels said.

She also thinks of the other companies coming behind Editas and Intellia who can look to their initial safety data to inform future trials.

“If you're chasing other people, it's good to have [safety data] knowing that we are going into something that's not quite so unknown anymore,” Michaels said.

More data are needed before Editas knows exactly how much improvement patients with LCA10 might gain from treatment with the gene therapy. But for patients who lost vision early in life, Michaels said even a little improvement goes a long way.

RELATED: Nobel Prize in chemistry goes to CRISPR pioneers Doudna, Charpentier

She tells the story of a 10-year-old boy who couldn’t go trick or treating for Halloween without holding his parents’ hand as he went around the neighborhood.

“The ability to be able to go out in dim light and trick or treat on his own would be a major empowering thing,” Michaels said.

Another patient just wants to see her grandchild’s face, while others want to be able to go out in dimmer light rather than being confined to outings in daylight.

“I mean, these are big differences for people that really affect their lives, so that's a good starting place,” Michaels said.

Editor's note: This story has been updated to include analyst commentary and the share moves.