New Medicines

Achromatopsia due to mutations in the CNGA 3 gene


New molecular entity
Applied Genetic Technologies Corporation
Applied Genetic Technologies Corporation

Development and Regulatory status

Phase II Clinical Trials
Oct 15Granted orphan drug status in EU [3].


An adeno-associated virus (AAV) gene therapy
This condition causes complete loss of cone function, while rod function is normal throughout the course of disease. Its prevalence is estimated to be about 1 per 30,000. Since cones are concentrated at the fovea then the macula and fovea are disproportionately affected [1].
Achromatopsia due to mutations in the CNGA 3 gene
Subretinal injection

Trial or other data

Nov 20ACTC announces 12-month ACHM data from the PI/II study (NCT02935517). Subjects are being enrolled sequentially in six groups. Subjects in Groups 1, 2, 3, 4, and 5 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Groups 3a and 4a will be 6 to 17 years of age and will receive corresponding dose levels to the adult groups. Subjects in Group 6 will be at least 6 years of age and will receive the maximum tolerated dose identified in Groups 1, 2, 3, 3a, 4, 4a, and 5. Data are from the original three dose groups (low, medium and high), as well as 6- to 9-month data at two higher dose groups (higher and highest groups in the January 2020 data release), and data for 6 paediatric subjects (three in each study; 12-17 years old) at the first of three planned dose levels. While some patients showed improvements in at least one measure of visual function, no consistent sustained improvements were observed based on current assessments within the dose groups tested. However, anecdotal statements and assessments from patient-reported outcome surveys continue to provide AGTC with confidence that patients are subjectively experiencing improved vision. Based on the characteristics of ACHM, AGTC continues to believe that longer treatment durations and/or focusing on younger patients may be necessary to fully realise the potential of this treatment. AGTC intends to complete the planned enrolment of pediatric patients in the two highest dose groups of the ongoing ACHM clinical trials and has amended the study protocol to allow enrolment of patients as young as four years of age and to include additional assessments such as functional MRI (fMRI) and improved color brightness tests [6].
Mar 20The company completes planned enrolment in all dose groups for adult patients (age 18 years or older), including the two higher dose groups and continues to enrol paediatric patients. In May 2020, the company reported that 15 patients dosed with rAAV2tYF-PR1.7-hCNGA3 demonstrated positive changes in light discomfort testing and improvement in visual function with a favorable safety profile and no dose-limiting inflammatory responses were observed [7].
Dec 19UK sites: NCT02935517 - none [4]
Jun 19To date, 27 patients have been dosed across the B3 and A3 Phase 1/2 trials. Safety data demonstrate a favorable profile, the Data Safety Monitoring Committee (DSMC) has supported continued dose escalation and dosing of pediatric patients. One of three patients at the middle dose level in each trial and two of three patients at the high dose level in the ACHM B3 trial have shown clinically meaningful improvements in light discomfort, defined as greater than one log lux change from baseline at three months. [5]
Mar 19PI/II study (NCT02935517) is recruiting [2].
May 17PI/II trial to assess the safety and efficacy of rAAV2tYF-PR1.7-hCNGA3 in patients with achromatopsia caused by mutations in the CNGA3 gene starts (NCT02935517). 24 patients will be recruited in the US & Israel. AGTC-402 will be administered to one eye by subretinal injection. The primary study endpoint will be safety and the secondary study endpoint will be efficacy; collection of these data is expected to complete Jun 19 [2].