Feb 8, 2022

AGTC Plans Further Clinical Development of Achromatopsia (CNGB3) Gene Therapy

Eye On the Cure Research News

Interim results for pediatric patients with CNGB3 mutations were encouraging

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Applied Genetic Technologies Corporation (AGTC), a developer of gene therapies for retinal diseases and other rare conditions, has reported continued, encouraging results for patients participating in its Phase 1/2 gene therapy clinical trial for achromatopsia caused by CNGB3 mutations. Three-month, interim data for pediatric patients was included in the latest report. The company is planning to further develop the CNGB3 gene therapy (AGTC-401) subject to discussions with the US Food & Drug Administration.

A total of 21 adults and 10 pediatric patients have been treated in the Phase 1/2, dose escalation clinical trial for AGTC-401. Data for patients in the trial have been collected for up to 24 months.

Three adults and four pediatric patients were treated with the second-highest dose (1.1E+12 vg/mL) in the AGTC-401 trial. Two adults and two pediatric patients at the second-highest dose had improvements in retinal sensitivity as measured by static perimetry. Two adults at that dose also showed improvements in light discomfort. The company plans to continue clinical development of AGTC-401 using the second-highest dose.

AGTC did not observe consistent evidence of biologic activity in the Phase 1/2 clinical trial for AGTC-402, a gene therapy for patients with achromatopsia caused by mutations in CNGA3. The company is therefore not continuing development of AGTC-402.

As previously reported, in both the CNGA3 and CNGB3 trials, treatment with the highest doses (3.2E+12 vg/mL) of AGTC-401 and AGTC-402, respectively, led to three cases of severe ocular inflammation in pediatric patients. Two of those cases have since fully resolved, and one continues to resolve, with all three patients’ best corrected visual acuity returning to baseline.

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.

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.