New Medicines

Achromatopsia due to mutations in the CNGB 3 gene


New molecular entity
Applied Genetic Technologies Corporation
Applied Genetic Technologies Corporation

Development and Regulatory status

Phase II Clinical Trials
Nov 21Release of 3-month data from the pediatric patients in the PI/II trial is expected in in Q4 21 [10].
Sep 21Based on data announced in Jun 21, AGTC intends to advance the ACHMB3 to the next stage of clinical development. The Company is drafting an End-of-Phase 2 briefing packet to submit to the FDA and expects feedback in H1 2022 [9].
May 21AGTC announces an expansion of its manufacturing and analytics capabilities to advance commercialisation of gene therapy product candidates by leasing a 21,250 square foot build-to-suit cGMP manufacturing facility adjacent to the its Florida facility. The new facility is expected to be operational in Q4 2022 [9].
May 20AGTC plans to release additional data for the adult dose groups in the PI/II study in H2 20, which will be used to inform decision-making regarding readiness to move the product candidates to pivotal trials [7].
Oct 15Also has orphan drug status in US [3].
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 CNGB 3 gene
Subretinal injection

Trial or other data

Jun 21AGTC reports 12-month data from its ongoing PI/II trial, including data from all adult and low-dose pediatric patients. ACHM CNGB3 demonstrated biologic activity based on improvements in visual sensitivity in the treated area as measured by static perimetry and light discomfort as measured by the Ocular Photosensitivity Analyzer (OPA) both of which were supported by additional anecdotal patient reports. In addition, the safety profile remained favorable. Additionally, the six pediatric patients have been enrolled in high dose groups 5a and 6a. One new SAE of significant inflammation considered a Suspected Unexpected Serious Adverse Reaction, or SUSAR, occurred in one patient at the highest dose group 6a. An additional pediatric patient at this same dose also had significant inflammation, which was considered an SAE but not a SUSAR, during approximately the same post-operative time frame has not required a subsequent procedure. To address the above safety events in pediatric patients, systemic and local steroid doses have been increased and patients are being monitored closely [9].
Nov 20AGTC releases 12-month data from the Pi/II trial in the original three dose groups (low, medium and high), as well as 6- to 9-month data at two higher dose groups. Plus data for 3 paediatric subjects (12-17 years old) at the first of three planned dose levels. Across all patients evaluated, the safety profile remains favourable. 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, the company continues to believe that longer treatment durations and/or focusing on younger patients may be necessary to fully realise the potential of the treatment. Encouraging early data that functional magnetic resonance imaging, or fMRI, may allow for monitoring changes in the visual cortex following treatment, which could provide a better understanding of the time course and impact of the product candidate on visual function. Enrolment has been hampered by the COVID-19 pandemic, but patients are now being screened at multiple sites. In addition, the study protocol has been amended to allow enrolment of patients as young as 4 years of age and to include both fMRI and improved colour brightness tests [8].
Jul 20PI/II trial (NCT02599922) is recruiting with collection of primary outcome data now anticipated to finish in Sep 21 [6].
May 20AGTC reports that 22 patients have been dosed with rAAV2tYF-PR1.7-hCNGB3 demonstrating positive changes in light discomfort testing and improvement in visual function with a favourable safety profile and no dose-limiting inflammatory responses were observed. The company also announced that it has dosed three paediatric patients in the study although they expect paediatric enrolment will continue to be challenging [7].
Mar 20AGTC completes planned enrolment in all dose groups for adult patients (age 18 years or older), including the two higher dose groups and the company continues to enrol paediatric patients [7].
Dec 19No UK trial sites [4]
Sep 19Latest safety and efficacy data released - 27 patients have been dosed. Safety data demonstrate a favorable profile. 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 trial (NCT02599922) is recruiting [2].
Feb 16AGTC in collaboration with the National Eye Institute initiates a PI/II trial of rAAV2tYF-PR1.7-hCNGB3, for the treatment of achromatopsia (ACHM) caused by mutations in CNGB3 gene (NCT02599922). The study is expected to enrol approximately 24 subjects, aged 6 years and older, in the US. The primary study endpoint will be safety and the secondary study endpoint will be efficacy. Collection of primary outcome data is expected to complete Jun 20 [2].