RARE Daily

AGTC Reports Serious Adverse Events in Three Patients

September 24, 2021

Applied Genetic Technologies Corporation reported serious adverse events in three patients in the highest dose cohort of its phase 1/2 trial of its experimental gene therapy in patients with achromatopsia, a genetic condition that causes loss of vision.

Achromatopsia (ACHM) is an inherited condition caused by mutations in one of several genes, with the two most common being mutations in either the CNGB3 or CNGA3 genes.  ACHM is associated with extremely poor visual acuity (most affected individuals are legally blind), extreme light sensitivity resulting in daytime blindness, and complete loss of color discrimination. There is no specific treatment for ACHM, although deep red tinted glasses or contact lenses can reduce symptoms of light sensitivity and daytime blindness.

AGTC is currently developing two separate AAV gene therapy product candidates for the two most prevalent forms of ACHM, caused by either a genetic mutation in the CNGB3 or CNGA3 genes. Together, these two genetic mutations account for up to 75 percent of the ACHM patient population. Based on evidence from preclinical data, AGTC is currently conducting two separate phase 1/2 clinical trials to evaluate the safety and efficacy of AAV gene.

In June, the company reported 12-month data from its ongoing phase 1/2 ACHM clinical trials, including data from all adult and low-dose pediatric patients. In the ACHMB3 trial, the candidate 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 both of which were supported by additional anecdotal patient reports. The company said the safety profile of the product candidate remained favorable.

Based on these data, AGTC intends to advance the ACHMB3 trial 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 the first half of 2022.

Additionally, the company recently announced enrollment of six pediatric ACHMB3 patients and five pediatric ACHMA3 patients in high dose groups 5a and 6a. Three new serious adverse events of significant inflammation, each of which are considered a Suspected Unexpected Serious Adverse Reaction, or SUSAR, occurred in pediatric patients at the highest dose group 6a.

Two of the three patients are in the CNGA3 trial, the other is in the CNGB3 trial and the company reported the events to the FDA according to regulatory requirements. An additional CNGB3 pediatric patient at this same dose also had significant inflammation, which was considered a serious adverse event but not a SUSAR, during approximately the same post-operative time frame and  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.

The company said no comparable inflammation has been seen in the six pediatric patients across both trials at dose group 5a, nor in any of the adult patients or the lowest dose group 4 pediatric patients, leading the company to believe it has identified the maximum tolerated dose in pediatric patients, one of the key objectives in the trial.

AGTC said these new data do not change its plans to continue development of the ACHM product candidates as the body of data gives the company confidence in its plan to move forward at appropriate doses.

Author: Rare Daily Staff

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