AGTC Provides Trial Design Update for its Phase 2/3 XLRP Clinical Trial

Applied Genetic Technologies Corporation provided additional information about the proposed design of the planned phase 2/3 trial for its X-linked retinitis pigmentosa (XLRP) clinical program, which is expected to commence in the first quarter of 2021, and new preliminary data on a higher dose Group 5 from the ongoing phase 1/2 XLRP trial.

“We are excited to close out our 2020 fiscal year with a path toward initiating a phase 2/3 trial for our XLRP program, and to provide new preliminary data for the higher dose Group 5 in our phase 1/2 trial, which supports inclusion of that dose level in the phase 2/3. In addition, we remain on track to report additional data readouts from all three of our clinical programs in the fourth quarter of the 2020 calendar year,” Sue Washer, President and CEO of AGTC, said in a company news release. “The advancements we are making in our clinical programs, highlighted by the proposed design of our planned phase 2/3 XLRP trial, underscore our continued progress.”

Recent Highlights

X-linked Retinitis Pigmentosa (XLRP)

The proposed design of the XLRP phase 2/3 trial is expected to include approximately 60 patients randomized across three arms: a low-dose group (1.2E+11 vg/mL the Group 2 dose from the ongoing Phase 1/2 trial), a high-dose group (1.1E+12 vg/mL the Group 5 dose from the ongoing phase 1/2 trial), and an untreated control group. The primary endpoint will be based on visual sensitivity, with a responder defined as having at least 7 decibel improvement in visual sensitivity in at least 5 loci at month 12, which is intended to represent a clinically meaningful benefit. Responder rates in each active arm will be compared to responder rates in the control arm. The company plans to submit a 6-month interim analysis of the data from the phase 2/3 to the FDA to obtain feedback on the company’s development plan to support approval. Based on any FDA feedback, the company may modify the final trial design, enrollment numbers, and/or statistical analysis plan. The company also will discuss with FDA the possibility of finalizing dose selection for the treatment of the contralateral eye based on this 6-month interim data. The company expects to begin enrolling patients in 1Q 2021 and to provide results from the 6-month interim analysis in 3Q 2022, dependent on future effects of the COVID-19 pandemic on clinical trial enrollment.

• Analysis of visual sensitivity data from patients in the ongoing phase 1/2 XLRP trial shows that 7 of 15 patients in Groups 2, 4 and 5 are responders at month 6 (month 3 in one case) based on the responder criteria defined above. Focusing on the phase 1/2 Group 5 dose group, a dose level that the company is planning to use as the high dose in the phase 2/3 trial, 4 of 7 patients met the response criteria. Of note, using the planned inclusion/exclusion criteria for the phase 2/3 trial, one phase 1/2 Group 5 patient would be removed such that the responder rate would be 4 of 6, or 67%.

• The company also plans to expand its ongoing phase 1/2 trial to include approximately 12 additional patients who will be masked and randomized to doses of 1.2E+11 vg/mL (Group 2 in original trial plan) and 1.1E+12 vg/mL (Group 5 in original trial plan). The company expects to begin enrolling these additional patients in 4Q 2020 and to provide results from a 3-month interim analysis in 4Q 2021, dependent on future effects of the COVID-19 pandemic on clinical trial enrollment.

• AGTC remains on track to provide 12-month data from the ongoing phase 1/2 trial by 4Q 2020 for Groups 1-4 to evaluate durability of effect and continued safety, as well as full 6-month data analysis for Groups 5 and 6 to evaluate safety and efficacy at higher doses.             

• The company remains on-track to have clinical trial material produced in time for the initiation of the phase 2/3 trial with its advanced manufacturing process that provides improved yields, purity and potency. 

Achromatopsia (ACHM)

• In January 2020, AGTC announced encouraging interim data from the dose-escalation cohorts of its ongoing phase 1/2 clinical programs in patients with ACHM due to mutations in the ACHM CNGB3 or ACHM CNGA3 genes. In March, AGTC completed the planned enrollment in all dose groups for adult patients (age 18 years or older), including the two higher dose groups, of both ACHM trials, bringing the total number of adults dosed to 15 in the ACHM A3 trial and 22 in the ACHM B3 trial.  Pediatric dosing is ongoing with four pediatric patients dosed in each trial to date. The Company expects that pediatric enrollment may continue to be challenging.
• The company plans to release additional data for the adult dose groups in 4Q 2020, which will be used to inform decision-making regarding readiness to move the product candidates to pivotal trials.

Preclinical Programs

AGTC’s preclinical pipeline includes two ophthalmology programs, one of which targets the dry form of age-related macular degeneration (AMD), and three programs targeting central nervous system (CNS) disorders. The CNS programs target adrenoleukodystrophy (ALD) and two additional rare genetic CNS indications—frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)—that have substantial patient populations and well-defined clinical phenotypes. AGTC also has collaborations with Otonomy and Bionic Sight for genetic forms of hearing loss and optogenetics, respectively.

Mobile Vision Testing Program

In June 2020, AGTC announced that it launched a mobile vision testing program to conduct follow-up assessments during the COVID-19 pandemic for patients enrolled in the company’s ongoing clinical trials in XLRP and ACHM. The mobile vision testing program is available to patients enrolled in AGTC’s clinical trials across the United States so that they are able to maintain their follow-up study assessments while COVID-19 restrictions remain in effect. To date, more than 25 patients have been seen in the mobile vision testing program.