An experimental gene editing therapy for an inherited form of blindness has become the first in vivo CRISPR medicine to be administered to patients, according to Editas Medicine Inc. and its partner, Allergan plc, which licensed the candidate in 2018. Partners since March 2017, the companies are sponsoring a phase I/II trial to evaluate AGN-151587 in about 18 participants with Leber congenital amaurosis 10 (LCA10). The trial, called Brilliance, started at the Oregon Health & Science University's Casey Eye Institute, and could yield initial data as early as this year.

LCA10 is caused by mutations in the centrosomal protein 290 (CEP290) gene, which encodes CE, a protein required for the survival and proper function of photoreceptor cells. Its global incidence is estimated to be two to three per 100,000 live births worldwide. Editas estimates there are 2,000 to 5,000 patients with the condition in the U.S. and Europe. In the Brilliance trial, announced March 4, investigators will evaluate AGN-151587 in about 18 of those individuals, ages 3 to 17.

Participants in the study, split into up to five cohorts across three doses, will receive a single dose of AGN-151587, administered via subretinal injection in the study eye. While primary endpoints will focus on typical measures of safety, secondary endpoints will take account of functional measures, such as changes from baseline in participants' abilities to navigate an obstacle course and best-corrected visual acuity.

The study has been slow to start. Plans to file an IND for the open-label, single ascending-dose trial, first targeted for the end of 2017, were later adjusted to target mid-2018 to accommodate delays in third-party manufacturing and adjust to the new Allergan alliance. When it was later filed in October 2018, the IND outlined a plan to initiate patient screening in mid-2019 and begin patient dosing in the second half of 2019.

While enrollment in the trial eventually started, in July 2019, "initial dosing was delayed from the anticipated 2H19 time-frame due to the restrictive enrollment criteria for the first adult cohort (namely an adult patient with light perception only)," Chardan analyst Geulah Livshits wrote on Wednesday. "We understand the second patient would have similar criteria. Per management, patient screening is going well, and we would anticipate fewer issues with enrolling patients for subsequent cohorts."

Contrast and competition

Though one therapy for LCA, Roche Holding AG's Luxturna (voretigene neparvovec), has already won global approvals, that medicine is for patients with LCA due to mutations in the RPE65 gene, or LCA2. LCA10, by contrast, is caused by autosomal recessive mutations in the CEP290 gene.

AGN-151587, also known as EDIT-101, facilitates AAV-mediated editing by way of Editas' proprietary Staphylococcus aureus Cas9 (SaCas9) enzyme. It uses an AAV5 vector to deliver DNA encoding SaCas9 and two guide RNAs to photoreceptor cells in the eye. The approach is designed to "eliminate a disease-causing A to G nucleotide change in a noncoding region, or intron, of the CEP290 gene by cutting out that nucleotide and surrounding DNA," the company explained in a recent regulatory filing.

Editas and Allergan's primary competition in the LCA space comes from Proqr Therapeutics NV, which is recruiting patients for a pivotal trial of its own LCA10 candidate, sepofarsen, following a successful phase I/II study. It that trial, sepofarsen was observed to be well-tolerated with "rapid, significant and durable improvements" in vision maintained at month 12 of evaluation, the company reported. Top-line data from Proqr's study, called Illuminate, are expected during the first half of 2021.

Meanwhile, Editas is carrying ahead with other programs in its pipeline, including EDIT-102, a potential in vivo therapy for Usher syndrome 2A – another area of competition with Proqr – and EDT-301, a preclinical candidate from the other pillar of Editas' platform, engineered cell medicines. That platform, which focuses on editing cells outside the body before administering them to patients, is focused on hemoglobinopathies, starting with sickle cell disease and beta-thalassemia.

Editas' 2020 priorities, outlined by company President and CEO Cynthia Collins at Cowen and Co.'s 40th Annual Health Care Conference on Wednesday, include filing an IND for EDIT-301 and arriving at a development candidate for autosomal dominant retinitis pigmentosa 4, both by the end of 2020. Collins said her team will also seek to leverage its learnings from AAV in other therapeutic areas, such as neurological diseases.

The company is also developing its oncology efforts, in which Collins said the company sees opportunities to provide "off-the-shelf convenience with the ability to perform an essentially infinite number of genetic changes." Within the company's wholly owned oncology programs, it’s primarily focused on using engineered NK cells from induced pluripotent stem cells and healthy donor-derived NK cells edited to treat solid tumors. The company is collaborating with Bluerock and Sandhill Therapeutics Inc. to advance its technical capabilities in engineered cell medicines.

In November 2019, Editas said it amended its collaboration with Celgene Corp. (now Bristol-Myers Squibb Co.) to limit that partnership to just alpha-beta T-cell medicines, regaining rights to develop gamma delta T-cell therapies for the treatment of cancer and autoimmune diseases.

Shares of Editas (NASDAQ:EDIT) rose $1.05, or 4.8%, to close March 4 at $23.01.