CNGB3 Achromatopsia Gene Therapy Improves Visual Sensitivity


Clinical development will be stopped on the CNGA3 achromatopsia program as no clinical improvements were seen.

AGTC-401, a gene therapy developed by Applied Genetic Technologies Corporation (AGTC), has demonstrated continued efficacy in CNGB3 achromatopsia, according to new, 3-month pediatric findings from the phase 1/2 study (NCT02599922).

The candidate yielded robust improvements in visual sensitivity in both adult and pediatric patients. Despite previous Suspected Unexpected Serious Adverse Reactions (SUSARs), the safety profile continues to be acceptable, with no new SUSARs.

“The three-month pediatric findings provide further evidence for the strong potential of our product candidate for patients with ACHMB3, and we look forward to continuing our discussions with the regulatory agencies to determine the best path forward to bring this important therapy to patients,” Sue Washer, president and chief executive officer, AGTC, said in a statement. “We understand the challenges that patients with achromatopsia face in their daily lives and our team remains dedicated to advancing this program toward commercialization. These additional data provide us the opportunity to help inform the next phase of clinical development and we thank the patients and investigators for their participation in this important clinical trial.”

The new data reports on 3-month pediatric results and adult safety findings for up to 24 months. Pediatric data, from 7 patients, demonstrated efficacy and safety in this new population. The trial has dosed 21 adults over a 100-fold dose range in 5 groups and 10 pediatric patients at the 3 highest dose groups. The company has identified 1.1 x 1012 vg/mL as an ideal, well-tolerated and efficacious dose in both adult and pediatric patients.

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Both the CNGB3 and the parallel, phase 1/2, CNGA3 achromatopsia trial (NCT02935517) assessing AGTC-402 have been well-tolerated, with no new SUSARs after the previously reported SUSARs of severe ocular inflammation in 3 pediatric patients treated with the highest doses in both trials. Inflammation has improved with steroids; two cases have fully resolved and 1 continues to resolve, with all patients best corrected visual acuity returning to baseline.

However, AGTC also reported that the company would not be supporting further clinical development of AGTC-402 for patients with CNGA3 achromatopsia as there were no indications of clinical improvement. The company stated that mutant proteins present in patients with CNGA3 mutations and not CNGB3 mutations may have impacted the efficacy of AGTC-402 in that population.

Investigators assessed efficacy in the CNGB3 population via standard visual function tests and found that 2 of 4 pediatric patients and 2 of 3 adult patients in the 1.1 x 1012 vg/mL group were defined as responders in terms of visual sensitivity and quality of life improvements. The 2 other pediatric patients in this dose group and 3 others in the 3 x 1012 vg/mL dose group were unable to complete the visual sensitivity testing due to a lack of concentration and the company plans to adapt testing for younger patients.

“We’re pleased to have identified a generally safe and well tolerated dose of AGTC-401 for both adults and pediatric patients when inflammation is controlled,” investigator Robert Sisk, MD, director, pediatric vitreoretinal surgery and ophthalmic genetics, Cincinnati Children’s Hospital and the Cincinnati Eye Institute, added to the statement. “Based on the available pediatric data at three months, which are consistent with previously reported results in adults with ACHMB3, we are encouraged by the biologic activity observed in patients treated with AGTC-401. The achromatopsia community currently faces a significant unmet need and the totality of this data reinforces the promise of AGTC-401 as a potential treatment option if confirmed in future studies.”

Final analysis for both the CNGB3 and CNGA3 trials will be presented at future scientific conferences and published. AGTC plans to meet with the FDA in the first half of 2022 for an end-of-phase 2 meeting to advance the clinical development of AGTC-401 at the 1.1 x 1012vg/mL dose based on these positive data, from 31 patients over 2 months.

AGTC announces robust improvements in visual sensitivity in adult and pediatric patients, and plans to continue clinical development of AGTC-401 in patients with CNGB3 achromatopsia. News release. Applied Genetic Technologies Corporation. February 8, 2022.
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