More than two years after Editas Medicine launched the first clinical trial of a CRISPR-based gene editing treatment that works inside the body, the company finally has results to share with the world.
The data, announced by Editas and set to be presented at a medical conference Wednesday, offer some hopeful signs the company's therapy could help treat an inherited form of vision loss. But the small number of patients involved, as well as the limited follow-up afterwards, make the results difficult to interpret.
Still, the study findings are another milestone for a research field that's only recently begun to deliver clear evidence that CRISPR gene editing can treat human disease. They are also long anticipated for Editas, one of the first biotechs formed to turn the Nobel Prize-winning technology into medicines after its discovery a decade ago as a potent tool to alter DNA.
Editas' therapy is designed to correct a rare genetic defect in the light-sensing cells of the retina that causes progressive deterioration in vision. People with the condition, a few thousand of whom are estimated to live in the U.S. and Europe, are typically diagnosed as blind in infancy or early childhood.
Using CRISPR, Editas aims to restore those cells' function by editing the mutated gene, known as CEP290. (Sometimes called Leber congenital amaurosis Type 10, the disease is also referred to as CEP290-related retinal degeneration.)
"The hope is that if we can correct the genetic defect and restore photoreceptors' function, then that might restore vision to the treated patient," said Eric Pierce, director of the Ocular Genomics Institute at Massachusetts Eye and Ear and an investigator in the trial.
Initial results from the first six study participants indicate treatment, which was administered via a sub-retinal injection in one eye, was largely safe. No serious side effects or toxicity, like loss of light perception or persistent inflammation, were reported, Editas said. Some patients had mild, treatment-related inflammation that was controlled with steroids. Four experienced eye pain.
Mild inflammation and pain are also often associated with the injection and related surgery, according to Mark Pennesi, chief of the ophthalmic genetics division at Oregon Health & Science University's Casey Eye Institute and a trial investigator. Pennesi is presenting the study results Wednesday at the 19th International Symposium on Retinal Degeneration.
Efficacy data were more mixed, however. Editas set up its study to test three different doses of its therapy, known as EDIT-101. The lowest dose — given to the first two patients enrolled — was principally meant to assess safety and potential risks, said Lisa Michaels, the company's chief medical officer.
"They were treated with what was predicted to be the lowest dose that might provide benefit," said Michaels, who joined Editas from Bayer last November.
Treatment led to "indeterminant changes" and "variable data outcomes," respectively, for those patients on two measures of visual function and a maze-like test used by Editas to assess functional sight, according to a company presentation.
Results from the middle dose were more promising, particularly for the first patient enrolled into that group, a 54-year old woman with severe vision loss. Early changes on all three measures were sustained at six months, Editas said, showing improvements in visual acuity, retinal sensitivity and her ability to navigate the maze at lower light levels.
"I can see lines more clearly now. I have been able to find things on the floor with my eyes sometimes," Editas quoted the patient as saying in its presentation on the data. "This is not all the time, but I have been able to notice objects on the floor more than before the treatment."
Pennesi, the trial investigator, said her visual acuity was still below the level of legal blindness, but noted "it's a big improvement."
The next two patients given a middle dose of EDIT-101 didn't experience as pronounced an effect, however. The second had improved retinal sensitivity but no significant change in visual acuity. Results through the first three months for the third patient were "indeterminant," Editas said in its presentation.
Follow-up was less for those two, at five and three months respectively. Both Pierce and Pennesi suggested they may experience more benefit over time.
"We know with these therapies that even when you physiologically improve the retina, it sometimes takes time for brains to use that vision," Pennesi said.
A fourth patient was also treated in the mid-dose group but had not been tracked for at least three months at the time of data cut-off. Enrollment is proceeding for the high dose group, as well as for a pediatric cohort.
No treatments are available for CEP290-related retinal degeneration. But another company, ProQR Therapeutics, is developing a different kind of genetic medicine to treat it and has delivered encouraging early results. Data from a late-stage study are expected in the first half of next year.
A long road
The limitations to the data Editas disclosed Wednesday may disappoint some, particularly as the trial has been underway for more than two years. But Michaels, the CMO, said the company needed to show the progress that it's made.
"At the end of the day, I'll be honest with you, it was a calculus of: 'this trial has been going on for so long and we haven't been communicating,'" she said. "I thought it was important to come out with data."
A good part of the delays Editas has experienced were due to the pandemic, which forced many clinical trials across the country to pause last spring, just as the first patient was treated at Oregon Health & Science University in March 2020. (That patient, for example, was unable to return to Oregon for follow-up study visits due to COVID-19, meaning Editas only has efficacy data through six months.)
But the company has also undergone significant changes in leadership since 2019, when Katrine Bosley stepped down as CEO. Since then, almost all of Editas' executive team has been replaced. Michaels' predecessor as CMO, for instance, was with the company for only a year.
Veteran biotech executive James Mullen, who Editas appointed as CEO in February, acknowledged in a May interview with BioPharma Dive that the turnover has had an impact.
"There has been more churn at the senior level than ideal," he said. "Stability through the ranks is important when you're trying to do hard things."
The delays to Editas' trial has meant the company's gene editing peers have grabbed the CRISPR field's recent headlines.
CRISPR Therapeutics and partner Vertex have now treated several dozen people with their gene editing therapy for sickle cell and beta thalassemia, and could discuss an approval filing with the Food and Drug Administration within next year or so. Intellia Therapeutics, meanwhile, disclosed in June early data from a study of a rare disease treatment, beating Editas to become the first company to report clinical evidence of successful CRISPR gene editing inside a person's body.
For CRISPR research, Wednesday's data are another step forward. "We're helping usher in one of the next phases of genetic medicine," said Pierce of Mass. Eye and Ear.
For Editas, they are a "turning point," said Michaels.