The annual meeting of the American Society of Retina Specialists featured four days of scientific sessions. Among the notable updates on key clinical trials from the podium at ASRS are these four from regular Ophthalmology Innovation Summit participants.
REGENXBIO Crafts a Trial Protocol
Standardizing a surgical approach and then developing a viable study protocol for a clinical trial in retina is challenging, but REGENXBIO has taken a step forward in development of its RGS-314 gene therapy for neovascular age-related macular degeneration (AMD) by developing such a protocol, Jeffrey Heier, MD, of Boston reported.
RGX-314 is an adeno-associated virus serotype 8 vector that delivers an anti-VEGF fab protein. Study investigators developed an automated subretinal delivery process to deliver the gene therapy construct. The Phase I trial will explore three doses of RGX-314 in a dose-escalation regimen with six subjects per arm. The trial will enroll patients who have demonstrated a treatment response and frequent need of anti-VEGF therapy. Subjects will receive gene therapy and be followed for 24 months to evaluate safety and evidence of a biological effect.
The automated subretinal delivery process delivers RGX-314 via a vitrectomy machine using a MedOne Microdose Injector syringe.
To watch the presentation of REGENXBIO CMO Stephen Yoo, MD at OIS@ASRS, click here.
Dr. Heier is a consultant and has other financial interests in REGENXBIO.
Early Opthea OPT-302 Results Encouraging
Inhibition of VEGF-C/D by intravitreal injections of OPT-302 (Opthea) in doses up to 2 mg and combined with ranibizumab (Lucentis, Roche/Genentich) has proved to be well tolerated and feasible in patients with neovascular AMD, according to first-time Phase I/IIa results Pravin Dugel, MD, of Retinal Consultants of Arizona presented.
OPT-302 is a biological inhibitor of VEGF-C/D that reduces vascular leakage and neovascularization in mouse models. VEGF-C/D has been associated with suboptimal response to anti-VEGF-A therapy. The Phase I/IIa study aimed to determine the effects of OPT-302 alone or with Lucentis in 51 patients with wet AMD.
Dr. Dugel reported that all doses of intravitreal OPT-302 with or without Lucentis were safe and well tolerated. The investigators observed no dose-limiting toxicities and therapy did not reach a maximum-tolerated dose with OPT-302 up to 2 mg. There were no treatment-related serious adverse events. The most common treatment-emergent adverse events were conjunctival hemorrhage, punctate keratitis, and eye pain, which were mostly mild and manageable and related to the intravitreal injection, Dr. Dugel said. Analysis of changes from baseline in visual acuity and anatomical measures on spectral-domain optical coherence tomography (SD-OCT) following the three-month dosing period demonstrated preliminary clinical activity.
Watch CEO Megan Baldwin present an update on the company at OIS@ASRS here.
Dr. Dugel is a consultant and investigator and receives a honorarium from Opthea.
Spark’s VN Maintains Efficacy up to Four Years
Spark Therapeutics’ voretigene neparvovec (VN) for treatment of biallelic RPE65-mediated inherited retinal disease (IRD) has been shown to maintain functional vision/visual function improvements for up to four years after initiation of treatment, according to results of a follow-on Phase I clinical trial that Albert M. Maguire, MD, of the University of Pennsylvania and Children’s Hospital of Philadelphia, reported on.
The Food and Drug Administration has accepted Spark Therapeutics’ Biologics License Application (BLA) and granted Priority Review for voretigene neparvovec, a potential one-time gene therapy candidate for biallelic RPE65-mediated IRD. It could be not only the first pharmacological treatment for IRD, but also the first gene therapy in the US for a genetic disease. The proposed trade name for VN is Luxturna.
The follow-on Phase I trial involved administering VN to the second eye of subjects with biallelic RPE65-mediated IRD. The subjects showed marked improvement in their ability to navigate in varying light levels, as measured by a multi-luminance mobility test and full-field light sensitivity threshold (FST) testing, Dr. Maguire said.
Eleven subjects received subretinal injections of 0.3 mL of VN in the contralateral, injection naive eye at 1.7 to 4.6 years after initial unilateral injection. Compared with baseline, the subjects showed a greater than 100-fold average improvement in FST, which they maintained over four years, Dr. Maguire noted. No serious adverse events associated with VN or deleterious immune responses were observed.
Dr. Maguire is a paid investigator for Spark Therapeutics.
Luminate Measures Up to Avastin in DME
Three doses of anti-integrin ALG-1001 (Luminate, Allegro Ophthalmics) monotherapy demonstrated non-inferiority to six doses of bevacizumab (Avastin, Roche/Genetech) in patients with diabetic macular edema (DME) at 20 weeks, David S. Boyer, MD, reported.
ALG-1001 is a synthetic RGD-class oligopeptide that inhibits integrin receptors in vitro and arrests aberrant blood vessel growth in vivo meditated by αvβ3, αvβ5 as well as α2β1 and α5β1 – integrin sites expressed in neovascular ocular tissue from patients with diabetic retinopathy. The goal of the Phase IIb study is to investigate the safety and efficacy of Luminate versus Avastin in patients with DME.
Dr. Boyer reported that the study compared continuous monthly Avastin with 12 weeks post loading with Luminate at 20 weeks. The mean (SD) changes in best-corrected visual acuity (BCVA) were 5.2 (6.86), 2.7 (7.31), –1.5 (9.97), and 7.0 (8.21) letters gained in the 1-, 2-, and 3-mg Luminate versus 1.25-mg Avastin groups, respectively. The mean (SD) changes in central macular thickness (CMT) were –77 (141), –16 (110), –1 (152), and –104 (107) mm, respectively. There were no drug-related serious adverse events in the Luminate groups.
The primary endpoint of non-inferiority in BCVA at week 20 was met with 5.2 letter versus 7 letter gains in the 1-mg Luminate versus 1.25-mg Avastin groups. The secondary endpoint of non-inferiority in CMT at week 20, as measured with OCT, was met with –77 mm versus–104 mm in the 1-mg Luminate versus 1.25-mg Avastin groups.
Vicken Karageozian, MD, president and CMO, presented earlier in the week at OIS@ASRS. Watch here.
Dr. Boyer disclosed he serves on the advisory board of and holds stock in Allegro Ophthalmics and receives a honorarium from the company.
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