First Results From Editas CRISPR Eye Therapy Underwhelm Investors
Safety Is Reassuring But Efficacy Unclear
Executive Summary
While rivals Intellia impressed with their first in vivo CRISPR gene-editing data, Editas’s first results in just two patients are not enough to convince investors.
Shares in Editas Medicine have dropped 18% after the company shared the first results for EDIT-101, its CRISPR-based in vivo gene-editing treatment for rare eye disease Leber congenital amaurosis 10 (LCA10).
The company presented data from the first six patients to receive sub-retinal injections of the gene-editing therapy at low and mid doses, and although there were no serious safety issues, the results were modest with respect to efficacy.
Analysts were reassured by an absence of serious adverse events and dose-limiting toxicities in EDIT-101 after at least three months following treatment, with no immune response to the Cas9 gene-editing protein and no treatment-related cataracts, edema or retinal thinning observed to date.
Only the second in vivo CRISPR therapy to report clinical results so far, EDIT-101 delivers CRISPR cas9 gene-editing enzymes to the eye using an AAV viral vector, where it is designed to permanently remove the IVS26 mutation on the CEP290 gene.
But efficacy results from the open label Phase I/II BRILLIANCE study were limited and inconsistencies in patient responses meant there was no clear sign that the therapy can help restore sight.
The results presented on 29 September by Editas were less compelling than the initial readout from another CRISPR in vivo treatment from Intellia and Regeneron in June. (Also see "Intellia Achieves Gene-Editing Breakthrough With First In Vivo CRISPR Therapy" - Scrip, 28 Jun, 2021.)
The company has a direct competitor in ProQR Therapeutics, whose candidate sepofarsen is an antisense oligonucleotide therapy but also targets the CEP290 gene in LCA10. That program is currently in Phase II/III and ProQR saw its shares rise as investors inferred that it had retained a lead over Editas. (Also see "ProQR Raises $90m To Advance Eye Disease Pipeline" - Scrip, 31 Mar, 2021.)
Tiago Fauth, an analyst at Credit Suisse said in a same day note that investor expectations of Editas had probably been too high and that greater clarity will come from the higher dose adult cohort and a mid-dose pediatric cohort, for which enrolment and treatment are underway.
Results
The preliminary data came from an adult low-dose cohort (6x1011 vg/ml) and an adult mid-dose cohort (1.1x1012 vg/ml), but only two participants from the second group produced signs of gene editing.
Chief medical officer Lisa Michaels said evidence that gene editing had occurred included improvements in patients’ vision as measured by full-field light sensitivity threshold (FST) testing, best corrected visual acuity (BCVA), or improved ability to navigate standardized navigation courses.
The two responders in the mid-dose cohort showed an inconsistent pattern of response, with Subject One experiencing improvements in sight sustained six months after treatment. Subject Two showed improvement in retinal sensitivity in the FST test but no improvement in vision.
Among the group, patients who experienced less improvement had been treated more recently, giving hope that benefits could emerge over time.
AbbVie Exit And A New CEO
Investors will also be wary about Editas’ chances of success with EDIT-101 for a number of other reasons. First is that partner AbbVie returned the rights to the program in August 2020, which has left the biotech without a big pharma partner on the project, raising the risk of failure in R&D and any future commercialization.
Luca Issi, an analyst at RBC Capital Markets, also cautioned that even with an approved therapy in LCA10, the commercial potential of the therapy would be limited, with the most comparable treatment on the market, Roche’s Luxturna (voretigene neparvovec-rzyl) earning only $90m annually three years after its approval.
James Mullen
Editas has also just announced that dosing of the first patient in another program, for sickle cell disease, will be delayed from the second half of 2021 to the first half of 2022, raising doubts about its competitiveness in a crowded field.
The company’s leadership is also just bedding in, with former Biogen head Jim Mullen having taken over as CEO in February 2021, and chief scientific officer Mark Shearman and chief medical officer Michaels also both new to their roles. Issi concluded that investors would also “await further clarity on the long-term corporate vision.”
That could come via Editas’s two early stage but potentially lucrative drug development alliances in oncology. The first is with Bristol Myers Squibb to develop engineered αβ T-cells to treat cancer and potentially autoimmune diseases and another with BlueRock Therapeutics to develop gene-edited natural killer cells from allogeneic pluripotent stem cells. (Also see "Deal Watch: Editas, BlueRock Ink Cross-Licensing Technology Collaboration" - Scrip, 3 Apr, 2019.)