Choroideremia Gene Therapy Moves into Phase 3 Human Study

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Nightstar Therapeutics, a retinal-disease, gene-therapy development company in the UK, is advancing its emerging gene therapy for choroideremia into a Phase 3 clinical trial known as STAR. The study will enroll approximately 140 patients at 18 clinical sites in the US, Europe, Canada, and South America.

To accelerate STAR trial enrollment, the company plans to recruit most patients from its ongoing NIGHT study for observing the natural history of disease progression in people with choroideremia.
Nightstar reported that visual acuity was maintained or improved, over a one-year follow-up period, in more than 90 percent of patients in its Phase 1/2 clinical trial for the gene therapy.
“We are very encouraged by the results of Nightstar’s Phase 1/2 trial and the initiation of the Phase 3 study,” says Stephen Rose, PhD, chief scientific officer, Foundation Fighting Blindness. “The continuing advancement of the company’s choroideremia gene therapy through the clinical trial process is great news for people affected by the devastating condition.”
Choroideremia affects approximately 1 in 50,000 people — 6,000 people in the US. As an X-linked condition, only males are usually affected — females are usually unaffected carriers. Mutations in the REP-1 gene lead to degeneration of the choroid — the vasculature that provides oxygen and nourishment to the retina. Photoreceptors, the cells that make vision possible, and a layer of supportive cells known as the retinal pigment epithelium, also degenerate in people with the condition.
Miguel Seabra, PhD, received more than $1.5 million from FFB for his efforts to characterize the REP-1 gene, develop a rodent model of choroideremia, and evaluate early versions of the REP-1 gene therapy in lab studies. FFB also funded Jean Bennett, MD, PhD, at Children’s Hospital of Philadelphia, for her choroideremia lab studies.
Nightstar’s choroideremia gene therapy is contained in a small drop of liquid, which is injected underneath the retina. A human-engineered virus — an adeno-associated virus or AAV — delivers healthy copies of the REP-1 gene to affected cells, compensating for the mutated copies.