Gene Therapy Treatments Are Filling Some Companies’ Pipelines

Gene Therapy Treatments Are Filling Some Companies’ Pipelines

Major pharma companies in ophthalmology aren’t the only ones making plays in the gene therapy space, as we reported last week. Mid-size and small companies are also making moves, as evidenced by Astellas Pharma’s acquisition last week of Quethera, which is pursuing a novel gene therapy program for treatment of glaucoma. This week, we look at Astellas’ move and seven other companies that are developing gene therapy products for ocular disease.

Astellas Acquires Quethera

Tokyo-based Astellas reportedly paid $109 million to acquire Quethera’s ophthalmic gene therapy program, which uses a recombinant adeno-associated viral vector system (rAAV) to introduce therapeutic genes into target retinal cells for the treatment of glaucoma. The lead candidate of the program has demonstrated significantly improved survival of retinal ganglion cells in preclinical models, Astellas reported in a press release.

“We believe the rAAV program has potential as a new therapeutic option for the treatment of refractory glaucoma through an intraocular pressure (IOP)-independent mechanism,” says Astellas president and CEO Kenji Yasukawa, PhD. “It would address a high unmet medical need in glaucoma patients who are at risk of losing their eyesight.”

Quethera CEO Peter Widdowson, PhD, states the deal allows the company to speed up its development program. Founding investor UK Innovation and Science Seed Fund backed the company with co-investment from Cambridge Enterprise in August 2015 and followed with subsequent investment. Quethera is based in Cambridge, UK, and will continue as a wholly owned subsidiary of Astellas.


REGENXBIO made a host of moves last week, punctuated by the release of interim Phase I results for RGX-314 as a one-time treatment for wet age-related macular degeneration (AMD). The company also announced a public stock offering intended to raise $175.5 million.

RGX-314 is based on the proprietary NAV technology platform. In the Phase I trial, 18 subjects with wet AMD received a single administration of RGX-314 across three dose cohorts (six participants in each cohort). To qualify for inclusion in the trial, participants were required to have a history of frequent anti-VEGF treatment (including at least four anti-VEGF injections in the eight months preceding trial enrollment) and a documented history of response to anti-VEGF therapy.

The trial design included doses of 3 x 109 (Cohort 1), 1 x 1010 (Cohort 2), and 6 x 1010 (Cohort 3) genome copies (GC)/eye. Subjects have been assessed every month to the six-month primary endpoint, with long-term follow-up continuing for 24 months. The interim data included safety and efficacy assessments, and subjects have been followed for an average of 11 months for Cohort 1, nine months for Cohort 2, and six months for Cohort 3. Through month six, best-corrected visual acuity assessments for subjects in Cohort 3 have a mean improvement in visual acuity. Three subjects from Cohort 3 have been free of anti-VEGF injections since the administration of RGX-314.

“We are very encouraged by the positive interim data for RGX-314 and the potential of NAV gene therapy as a one-time treatment for wet AMD, particularly as this is a non-rare patient population with a significant treatment burden,” says REGENXBIO president and CEO Kenneth T. Mills. The company anticipates presenting the trial results at the American Academy of Ophthalmology meeting in October.

AGTC Doses First Patient in Phase I/II

Applied Genetic Technologies Corporation, otherwise known as AGTC, is a biotechnology company conducting human clinical trials of AAV-based gene therapies for treatment of rare diseases. The company dosed the first patient in its Phase I/II clinical trial evaluating an investigational AAV-based gene therapy for the treatment of X-linked retinitis pigmentosa (XLRP).

The multicenter study will assess AGTC’s novel recombinant AAV vector expressing a human RPGR gene in patients with XLRP. The primary focus of the study will be to assess the safety of the vector through analysis of local (ocular) or systemic treatment-emergent adverse events. Efficacy will be measured by evaluation of changes in retinal structure, function, and quality of life.

The XLRP program is part of AGTC’s collaboration with Biogen. Under the terms of the collaboration, AGTC received a milestone payment of $2.5 million upon enrollment of the first patient in the XLRP trial. AGTC is also currently developing two separate AAV gene therapy product candidates for the two most prevalent forms of achromatopsia, caused by a genetic mutation in either the CNGB3 or CNGA3 genes.

GenSight Moves on Leber’s

GenSight Biologics is also using AAV vectors, focusing on the treatment of retinal diseases. The company’s two lead products are GS010 for treatment of Leber hereditary optic neuropathy (LHON) due to ND4 mutation, and GS030 for treatment of retinitis pigmentosa.

Earlier this summer the company held an event with key opinion leaders (KOLs) to discuss GS010 and the REVERSE Phase III clinical trial in the treatment of LHON. The KOLs agreed that the preservation of anatomical structures combined with visual function improvement (contrast sensitivity) shown in the trial demonstrates neuroprotection in human genetic disease, which is important for treatment of LHON. They also discussed the bilateral improvement that was seen, and deemed it clinically relevant, not the result of placebo effect or natural history. GenSight is committed to getting regulatory approval for GS010 in Europe and the US.

MeiraGTx and Ophthotech

MeiraGTx has four ongoing gene therapy clinical programs. On August 13 the company announced that the Food and Drug Administration had granted orphan drug designation for its AAV-CNGA3 gene therapy product candidate for the treatment of achromatopsia caused by mutations in the CNGA3 gene. The firm’s other programs include Phase I/II clinical-stage programs in X-linked retinitis pigmentosa, and RPE65-deficiency, and a Phase I program in radiation-induced xerostomia. In addition, MeiraGTx anticipates initiating a clinical program in xerostomia related to Sjogren’s syndrome in 2019 and having preclinical programs in neurodegenerative diseases.

Ophthotech recently entered into a collaboration agreement with the University of Massachusetts Medical School and the Horae Gene Therapy Center located there. The collaboration will focus on applying novel gene therapy technology to discover and develop therapies for the treatment of ocular diseases. Part of the collaboration will be focused on the researchers’ “minigene” therapy, which is a novel therapeutic strategy that seeks to deliver a shortened but still functional form of a large gene packaged into a standard-size AAV delivery vector commonly used in gene therapy.

This approach may offer a solution for diseases that would otherwise be difficult to address through conventional AAV gene replacement therapy where the size of the gene of interest exceeds the transgene packaging capacity of conventional AAV vectors.

Adverum and Horama

Adverum Biotechnologies says it is “advancing a robust pipeline of gene therapy product candidates targeting unmet medical needs in serious rare and ocular diseases.” The company’s programs include candidates for use in wet AMD, inherited retinal disease, and juvenile X-linked retinoschisis, as well as A1AT deficiency and hereditary angioedema.

The company recently announced that the first patient has been dosed in Cohort 3 of the ADVANCE trial for ADVM-043 in A1AT deficiency and says the safety and tolerability results seen so far have been encouraging. An investigational new drug (IND) submission has been completed for ADVM-022 for wet AMD, and an IND submission for ADVM-053 in hereditary angioedema is planned for the fourth quarter of this year.

French-based Horama late last year raised $21.6 million from new and existing investors to fund the development of gene therapy treatments for rare retinal diseases. In May the company named a new chairman, and it continues to move forward with programs to develop therapies for retinitis pigmentosa and retinal dystrophy. The firm has initiated a Phase I/II clinical trial for HORA-PDE6B and enrolled its first patients. The study aims to evaluate the safety and efficacy of HORA-PDE6B in the treatment of retinitis pigmentosa caused by mutations in the PDE6B gene. The HORA-PDE6B drug candidate, which is administered unilaterally in the subretinal space, replaces the defective gene with a non-mutated copy of the PDE6B gene, to express a functional PDE6β protein.

This is an incomplete list of course, but one that demonstrates the level of activity occurring in the development of gene therapies for AMD and rare, inherited retinal disease. Continued collaboration, research, and development of treatments could result in major breakthroughs in the lives of patients with ocular disease.

For questions about this article, please contact Steve Lenier at