Gene therapy company Applied Genetic Technologies Corporation (AGTC) reported positive interim 6-month data from its ongoing phase 1/2 clinical program in X-linked retinitis pigmentosa (XLRP). The results show that patients treated centrally with its product candidate demonstrated durable improvement in visual function 6 months after dosing. These data reinforce the promising efficacy and safety results reported in September 2019 and will help to design the XLRP pivotal trial that is currently being planned to initiate by the end of 2020, according to a company news release.
The company also remains on track to report interim 6-month data from the dose escalation cohorts of both of its ongoing trials in achromatopsia later this month.
Data from 17 of the 25 patients have been previously reported in September 2019 and demonstrated a favorable safety profile. Of the 17, eight peripherally treated patients showed stable visually function through 6 months and nine centrally treated patients showed improvement in visual function as measured by microperimetry and/or BCVA through 3 months.
At the 6-month time point for these same nine centrally dosed patients:
- Measurable improvements were observed in visual sensitivity for four of the evaluable eight patients. These are the same four patients discussed in September and indicate encouraging signs of a durable biologic effect. Patients are defined as responders with improvement in visual sensitivity within the treatment area that is beyond the testing variability on at least two different test dates.
- All nine patients treated centrally also had stable or improving visual acuity, 78% saw a 5 letter or more improvement, a result not reported in other XLRP trials.
- Patients who improved in either visual sensitivity or BCVA also anecdotally report noticeable improvement in visual function including greater clarity and reduced night blindness.
Preliminary data for additional patients enrolled at a new higher dose group are consistent with previous data.
In an exclusive interview with Eyewire News, Sue Washer, President and CEO of AGTC, discussed the most significant findings from the 6-month data. “I think the significant findings were the very compelling improvements seen in the eight evaluable patients. Four out of eight, or 50%, responded and had compelling improvements in visual sensitivity, and this was maintained all the way through the 6-month time point. That response rate was seen at 1 month, 2 months, 3 months, and 6 months. So that durable improvement in visual sensitivity for these patients we think was very compelling,” Ms. Washer said.
Safety data from all 25 patients dosed to date continue to demonstrate a favorable profile for the XLRP candidate, with no dose-limiting inflammatory responses observed and no secondary inflammatory responses requiring re-administration of any steroid in any patients.
The company is scheduling additional patients for enrollment during the first quarter of the 2020. These patients will enable AGTC to generate the most robust set of data possible as the company moves forward with planning for a pivotal trial and eventual BLA application.
“The sustained improvement in visual sensitivity in centrally dosed patients are compelling and, if confirmed in a pivotal trial, would be highly meaningful to patients,” Paul Yang, MD, PhD, Assistant Professor of Ophthalmology at the Casey Eye Institute, Oregon Health & Science University in Portland, said in the news release. “Additionally, this is the first investigational therapy for XLRP to report on encouraging improvements in visual acuity. The combination of improved visual function across two endpoints in centrally treated patients and the previously reported stabilization of visual function in peripherally dosed patients, suggest that this gene-based therapy has the potential to be an important new approach to treating XLRP.”