The World’s First In Vivo Study of a CRISPR-Based Genome Editing Medicine (Editing Inside the Body)

Jul 26, 2019 | CRISPR, Gene-Editing, Leber congenital amaurosis 10

The World’s First In Vivo Study of a CRISPR-Based Genome Editing Medicine (Editing Inside the Body)

Allergan (AGN) and Editas Medicine (EDIT) announced the Brilliance Phase 1/2 clinical trial of AGN-151587 (EDIT-101) is now open for patient enrollment. AGN-151587 is an experimental medicine for the treatment of Leber congenital amaurosis 10 (LCA10), an inherited from of blindness caused by mutations in the CEP290 gene. This clinical trial will incorporate the world’s first CRISPR editing within the human body!

TrialSite News breaks down this complicated study in the hopes of providing clarity to this investigational treatment, the study, and the companies.

What is Leber congenital amaurosis 10 (LCA10)?

LCA10 is an eye disorder that primarily impacts the retina, which is specialized tissue at the back of the eye that detects light and color. Patients with this disorder typically experience major visual impairment beginning in infancy. Although typically stable, it can worsen over time.

The condition is associated with other major problems as well, including photophobia, nystagmus and extreme farsightedness (hyperopia). With LCA10, eye pupils fail to react normally to light. Rather, they expand and contract more slowly than normal—or they may not respond to light at all. Moreover, the cornea may become con-shaped and abnormally thin.

What is AGN-151587?

Also known as EDIT-101, AGN-151587 is a CRISPR-based experimental medicine under investigation for the treatment of LCA10. AGN-151587 is administered via subretinal injection to reach and deliver the gene editing treatment directly to the photoreceptor cells.

The Allergan and Editas Medicine Alliance

The two ventures entered into an agreement in March 2017 to form a strategic alliance and option agreement under which Allergan received exclusive access and the option to license up to five of Editas Medicine’s genome editing programs for ocular diseases, including AGN-151587 (EDIT-101). Allergan is responsible for the development and commercialization of optioned products, subject to Editas Medicine’s option to co-develop and share equally in the profits and losses of two optioned products in the United States. The agreement covers a range of first-in-class ocular programs targeting serious, vision-threatening diseases based on Editas Medicine’s unparalleled CRISPR genome editing platform, including CRISPR/Cas9 and CRISPR/Cpf1 (also known as Cas12a).

Editas Medicine is also eligible to receive development and commercial milestones as well as royalty payments on a per-program basis.

What is the Brilliance Phase 1/2 Clinical Trial?

The study is an open-label, single ascending dose trial of AGN-151587 (EDIT-101) in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Approximately 18 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of AGN-151587 in this study. AGN-151587 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26. The study start date is July 31, 2019 and the estimated completion date is March 22, 2024.

Research sites for this study include:

  • Bascom Palmer Eye Institute, Miami, FL
  • Massachusetts Eye and Ear Infirmary, Boston, MA
  • W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI
  • Casey Eye Institute, Oregon Science & Health University, Portland, OR

What is the CEP290 Gene

The CEP290 gene provides instructions for making a protein that is present in many types of cells. Although this protein’s function is not well understood, studies suggest that it plays an important role in cell structures called centrosomes and cilia. Centrosomes are involved in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Cilia are involved in cell movement and many different chemical signaling pathways. They are also necessary for the perception of sensory input, such as vision, hearing, and smell.


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