AGTC Reports Encouraging Results from Phase 1/2 Gene Therapy Clinical Trial for Achromatopsia (CNGB3 Mutations)

Applied Genetic Technologies Corporation (AGTC), a developer of gene therapies for retinal diseases and other rare conditions, reported 12-month data for the ongoing Phase 1/2 clinical trials of its gene therapies for achromatopsia (CNGB3 and CNGA3 mutations). Twelve-month data were available for 45 patients (adult and pediatric) in the two trials. Overall, both gene therapies had favorable safety profiles. The Foundation funded lab studies that helped make the achromatopsia gene therapy clinical trials possible.

Achromatopsia is a debilitating inherited retinal disease causing extreme light sensitivity, loss of color perception, and poor visual acuity. Approximately 27,000 people in the US and EU are affected by achromatopsia. Five genes, when mutated, can cause achromatopsia. About 75 percent of cases are caused by mutations in CNGB3 or CNGA3.

The company is planning to move its CNGB3 gene therapy into a late-stage trial thanks to improvements in retinal sensitivity as measured by static perimetry and improvements in light discomfort as measured by an ocular photosensitivity analyzer. In the CNGB3 trial, improvements in retinal sensitivity were observed in four of 11 patients from the high-dose and pediatric groups. Improvements in light discomfort were observed in six of these 11 patients.

Patient anecdotes from the CNGB3 Phase 1/2 trial were also encouraging. For example, one patient said, “I can see details outside that I couldn’t see before — I can see bikes when I cross the street. I can see them without wearing tinted contacts and dark ski goggles.” Another patient commented, “My light sensitivity is markedly better than in my untreated eye and for the first time I can take my sunglasses off in an outdoor setting.”

AGTC did not observe consistent evidence of biologic activity in the CNGA3 gene therapy trial, though patient-reported anecdotes were encouraging.

The company will continue to dose pediatric patients in both Phase 1/2 CNGB3 and CNGA3 gene therapy trials.

AGTC believes that the difference in efficacy between CNGB3 and CNGA3 gene therapies may be due to differences in how the mutated genes express defective proteins in achromatopsia patients. Patients with CNGB3 mutations have no protein expressed. However, patients with CNGA3 mutations have defective proteins which may interfere with the function of the healthy protein expressed by the gene therapy. Investigations are ongoing to better understand the effect of defective protein expression in CNGA3 patients.