Preclinical success for Nightstar Therapeutics' (NASDAQ:NITE) and Applied Genetic Technologies’ (NASDAQ:AGTC) gene therapies for X-linked retinitis pigmentosa (XLRP) has experts on the fence of translation into the clinic. While animal studies have shown strong protein expression and even visual function recovery, a lack of understanding of XLRP-led photoreceptor cell death precludes confidence for a benefit in clinical trials, they said.
As Phase I/II trials are focusing on safety, experts note secondary efficacy outcomes of visual function and acuity in the escalation stage are unlikely to yield robust results. The dose-expansion phase with younger patients could show better results due to more intact cells, said experts, though overall small and inconclusive numbers draw caution.
Safety for these gene therapies -- both comprising an adeno-associated virus (AAV) vector with a retinitis pigmentosa GTPase Regulator (RPGR) gene -- are of low concern, backed by other AAV gene therapies including Spark Therapeutics’ (NASDAQ:ONCE) Luxturna (voretigene neparvovec-rzyl) approved for Leber’s congenital amaurosis, experts said.
All ongoing XLRP gene therapies are in Phase I/II, with Nightstar’s NSR-RPGR in a 24-patient XIRIUS trial (NCT03116113) expecting preliminary results in 3Q and Applied Genetic Technologies’ (AGTC's) rAAV2tYF-GRK1-RPGR in a 15-patient trial (NCT03316560), expecting preliminary results in 1Q19.
Analysts anticipate a 2022 launch for both NSR-RPGR and GRK1-RPGR, with sales of 299m and 158m in 2024, respectively. Nightstar has a market cap of USD 448m, and AGTC has a market cap of USD 77m.