FDA Approved First Anti-VEGF Agent for Myopic CNV
The US Food and Drug Administration (FDA) approved 0.5 mg ranibizumab (Lucentis, Genentech) for the treatment of myopic choroidal neovascularization (mCNV). This makes ranibizumab the first FDA-approved anti-VEGF agent for mCNV, and it is the fifth labeled indication for ranibizumab, according to the manufacturer.
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EyewireTV spoke with Anne Fung, MD, associate group medical director at Genentech, about the FDA approval of ranibizumab for mCNV.
The phase 3 RADIANCE trial was a 12-month, randomized, double-masked, multicenter, active-controlled study that evaluated 277 patients with visual impairment due to mCNV.1 Researchers randomly assigned patients to receive one of three regimens: ranibizumab on day 1, month 1, and as needed thereafter guided by visual acuity (VA) stabilization criteria; ranibizumab on day 1 and as needed thereafter guided by disease activity criteria; or verteporfin photodynamic therapy (PDT) on day 1, with disease activity treated with ranibizumab or PDT at investigators discretion after month 3.
Compared with patients assigned to the PDT group, patients who were assigned to the ranibizumab groups demonstrated superior average BCVA change from baseline at month 3. Patients in the ranibizumab groups demonstrated improvements of 12.1and 12.5 ETDRS letters at month 3 compared with improvement of 1.4 ETDRS letters in the PDT group (P .001).
Therapy guided by disease activity was noninferior to therapy guided by VA stabilization. Patients who received ranibizumab retreatment based on VA stabilization criteria gained 11.9 ETDRS letters, and patients who received therapy based on disease activity criteria gained 11.7 ETDRS letters.
At month 12, nearly two-thirds of patients showed resolution of myopic CNV leakage. No deaths or cases of endophthalmitis or myocardial infarction (MI) occurred.
1. Wolf S, Balciuniene VJ, Laganovska G, et al; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014;121(3):682-692.e2.
Phase 3 Anti-PDGF Studies for AMD Fail to Reach Primary Endpoint
A pair of phase 3 clinical trials evaluating the safety and efficacy of the anti-PDGF agent pegpleranib (Fovista, Ophthotech) in combination with ranibizumab for the treatment of wet age-related macular degeneration (AMD) failed to reach the primary endpoint, according to a company press release.
OPH1002 and OPH1003 were international, multicenter, randomized, double-masked, controlled phase 3 studies evaluating the safety and efficacy of 1.5 mg pegpleranib in combination with ranibizumab compared with ranibizumab monotherapy for treatment of wet AMD.
At 12 months, patients in the combination therapy arms, compared with those in the monotherapy arms, demonstrated no statistically significant differences in mean gain of ETDRS letters, percentage of patients who gained at least 20 ETDRS letters, percentage of patients who lost 5 or more ETDRS letters, or percentage of patients who achieved VA of 20/25 or better. See the Table above for more details.
Combination therapy and ranibizumab monotherapy were generally well tolerated after 12 months of treatment, and ocular adverse events were mainly related to the injection procedure. The incidence of reported serious systemic adverse events was similar in both groups, as was incidence of MI or cerebrovascular accident.
Study: Preeclampsia During Pregnancy Associated With Increased Risk of Retina Disease
Women who experienced preeclampsia during pregnancy were more likely to develop retinal disease decades later compared with women who did not experience preeclampsia, according to research published in Obstetrics Gynecology.1
Researchers performed a longitudinal cohort study that included 1.1 million women who delivered babies in Quebec, Canada, between 1989 and 2013, and tracked their later hospitalizations until March 2014. Severity and duration of preeclampsia was measured at delivery.
Compared with women with no preeclampsia, women with preeclampsia had a higher incidence of hospitalization for retinal detachment, retinopathy, and other retinal disorders. Women with preeclampsia were 2.4 times more likely to demonstrate tractional retinal detachments, 2.5 times more likely to demonstrate retinal breaks, and more than 4.0 times more likely to demonstrate diabetic retinopathy.
Severe and early-onset preeclampsia was associated with higher risk compared with mild or late-onset preeclampsia.
1. Auger N, Fraser W, Paradis G, et al. Preeclampsia and long-term risk of maternal retinal disorders. Obstet Gynecol. 2017;129(1):42-49.
Orphan Drug Designation Given to Drug Exploring Stargardt Disease Indication
The FDA granted orphan drug designation to emixustat HCl (Acucela) for the treatment of Stargardt disease.
Emixustat modulates the visual cycle by inhibiting RPE65 protein, which in turn reduces the availability of vitamin A derivatives to form precursors of the retina-damaging agent A2E, according to a press release from Acucela. The drug, which is delivered orally, was found to be well tolerated in clinical studies, with delayed dark adaptation as the most common ocular adverse event, according to the press release.
AAO Launching New Retina Journal
The American Academy of Ophthalmology (AAO) will launch a journal titled Ophthalmology Retina, with the first issue slated for January/February 2017, according to a press release.
Andrew P. Schachat, MD, who previously served as Editor-in-Chief of the AAO journal Ophthalmology from 2003 to 2012, will be Editor-in-Chief of Ophthalmology Retina.
The AAOs website reports that the journal will be published bimonthly during 2017 and then monthly in 2018. The journal is to be submitted for PubMed indexing. Until it is accepted for indexing, abstracts of articles appearing in Ophthalmology Retina will appear in Ophthalmology.
Subscriptions to the journal will cost $149 for AAO fellows and members in 2017 and $299 in 2018, the AAOs website states.
Second Stage of Phase 2b Study for Integrin Peptide Therapy for DME Completed Enrollment
Investigators have completed enrollment in the second stage of the phase 2b DEL MAR study, according to a press release.
DEL MAR is evaluating the safety and efficacy of ALG-1001 (Luminate, Allegro Ophthalmics) in combination with and as an adjunctive therapy to bevacizumab (Avastin, Genentech) in patients with diabetic macular edema (DME). Top-line results from the DEL MAR stage 1 monotherapy trial showed that the trial met its primary and secondary endpoints, demonstrating equivalence to bevacizumab monotherapy with half the number of injections, according to a press release.
The second stage of the phase 2b DEL MAR study is a double-masked, placebo-controlled, randomized, multicenter, 5-month trial evaluating the safety and efficacy of intravitreal ALG-1001 in patients with DME. Patients will be enrolled into one of five arms: ALG-1001 0.5 mg or ALG-1001 1.0 mg in combination with bevacizumab 1.25 mg intravitreal injections; ALG-1001 0.5 mg or ALG-1001 1.0 mg as an adjunctive therapy after treatment with a single bevacizumab 1.25 mg intravitreal injection; or bevacizumab monotherapy.
The company expects to report top-line data in the first half of 2017.
FDA Issues IDE for Telescopic Implant in Pseudophakic Patients
The FDA approved an investigational device exemption (IDE) for a US clinical trial evaluating the safety and efficacy of the Implantable Miniature Telescope (IMT; VisionCare) in patients who underwent cataract surgery and have been implanted with an intraocular lens (IOL), reported a company press release.
The IMT is indicated for monocular implantationin patients at least 65 years old with stable, severe to profound vision impairment caused by bilateral central scotomas associated with end-stage AMD. The device is contraindicated in patients with previous intraocular or corneal surgery of any kind in the operative eye, including any type of surgery for refractive or therapeutic purposes. In this trial, patients previously implanted IOLs will be exchanged for the IMT.
ForSight Vision4 Acquired by Roche
ForSight Vision4 was acquired by Roche Holdings, according to a press release from Roche Holdings.
In 2010, ForSight announced a collaboration and license agreement with Genentech that granted exclusive access to Forsights port delivery system (PDS) technology for long-acting delivery into the vitreous of therapeutic agents targeting VEGF-A. Genentech is also part of the Roche Group.
The PDS, which is surgically implanted into the sclera, can be refilled with an anti-VEGF agent by a physician using a proprietary refill needle in an office setting. The phase 2 LADDER study, which is evaluating the PDS in conjunction with ranibizumab, aims to define the duration of drug delivery possible with PDS technology.
Oculus Released Smaller Surgical Lens
Oculus has released a 17-mm version of the WiFi HD lens for its BIOM viewing system, according to a press release from the company. The new, thinner lens is called the WiFi HD Mini lens.
The company designed the lens in response to customer suggestions that the WiFi HD lens would cause less interference during surgical procedures if the diameter were reduced, noted the press release. The WiFi HD Mini lens is designed to provide the same range of surgical procedures allowed by the WiFi HD.
Phase 2 Trial for Anti-PlGF Agent for DME Enrolls First Patient
The first patient has been enrolled in a phase 2 trial evaluating THR-317 (ThromboGenics), an antihuman placental growth factor (anti-PlGF) agent, for the treatment of DME.
The phase 2, single-masked, multicenter exploratory study will evaluate the safety of three intravitreal injections of THR-317 in 4- and 8-mg doses. Primary endpoints include BCVA improvement from baseline and reduction of central retinal thickness in patients with DME.
The company plans to enroll 50 patients over a 1-year period and expects the first results to be announced in early 2018.