Jetrea Post-marketing Experience Is No Surprise
Patient selection is key; AEs tend to be transient.
BY JERRY HELZNER, CONTRIBUTING EDITOR
■ Since the FDA approved Jetrea (ocriplasmin, ThromboGenics, Iselin, NJ) in 2012 as the first medical treatment for symptomatic vitreomacular adhesion (VMA), the drug has been the subject of a number of studies and anecdotal reports that essentially focus on two major issues: adverse events (AE) and the importance of patient selection.
ThromboGenics has been proactive in addressing these issues, recently announcing its own ongoing safety study with Carl Regillo, MD, of Wills Eye Hospital in Philadelphia, PA, and Pravin Dugel, MD, of Phoenix, AZ, as monitors. Dr. Dugel has promised regular updates on all information reported to five AE registries, including the 1,500-patient ORBIT safety study ThromboGenics itself has undertaken.
As studies on post-marketing experiences with ocriplasmin continue — ARVO 2014 was treasure trove of such studies — two major findings involving patient selection and safety have become increasingly validated. These findings have been consistent with the pivotal MIVI-TRUST trials (N Engl J Med. 2012; 367:606-615).
Success with ocriplasmin largely depends on patient selection
The MIVI-TRUST and post-marketing studies have demonstrated that specific factors, including age of 65 years and younger, absence of epiretinal membrane (ERM), VMA no larger than 1,500 µm, and phakic lens status, were more associated with VMA release after treatment with ocriplasmin. In addition, macular holes smaller than 250 µm were more likely to close than medium-sized ones.
For example, in MIVI-TRUST, patients without ERMs treated with ocriplasmin had a rate of VMA resolution of 37.4%, compared to 14.3% of patients receiving placebo. But only 8.7% of patients with an ERM treated with ocriplasmin had VMA release.
In a compilation of nine independent post-marketing studies, ThromboGenics reported an overall mean VMA resolution rate of 43%, which the company attributes to better patient selection. Again, in these studies the rate of resolution in patients with ERMs was low.
Adverse events tend to be transient and mild
In both the MIVI-TRUST and recent post-marketing studies, ocriplasmin injections were well tolerated. Reported AEs included symptomatic vitreous floaters, photopsia, conjunctival redness, and irritation. These events appeared to be related to the procedure of intravitreal injection rather than specifically to ocriplasmin. These events were transient and mild in most cases.
In a compilation of 6,903 post-marketing ocriplasmin doses presented at ARVO 2014, ThromboGenics reported across-the-board rates of adverse drug reactions were comparable or slightly lower than those the MIVI-TRUST trial reported.
As more data are reported to the various ocriplasmin registries in the coming months, retina specialists will be able to obtain additional information that can guide them in the areas of safety and appropriate patient selection.
■ Italy to Reimburse Avastin for Wet AMD In a controversial decision aimed at cutting increasing health-care costs, the Italian Medicines Agency has approved reimbursement for the use of off-label Avastin (bevacizumab) for treatment of wet AMD. The move is considered unusual because the use of drugs for unapproved indications has long been discouraged — and often prosecuted — in the European Union.
Roche, the developer of Avastin has protested the decision on safety reasons. The Italian antitrust authority has already accused Novartis/Roche of colluding to prevent the use of Avastin for retinal disease and is seeking monetary damages.
Encouraging Data on Stem Cell Trial
GA rate of progression is sharply reduced.
■ StemCells, Inc., (Newark, CA) reported positive interim results from its phase 1/2 clinical trial of the its proprietary HuCNS-SC(R) human neural stem cell platform in dry AMD in late June at the 12th annual meeting of the International Society for Stem Cell Research (ISSCR) in Vancouver, BC. The seven-patient trial is designed to determine if the rate of progression of geographic atrophy (GA) can be slowed or halted through the use of stem cell transplants.
At 12 months, trial results showed an average 65% reduction in the rate of GA progression in the study eye compared to the expected natural history of the disease as well as an average 70% reduction in the rate of progression of GA vs the control eye. Interim results also indicated improvements in visual function, as measured by contrast sensitivity. Contrast sensitivity was improved in four of the seven patients and remained stable in the other three patients.
The interim analysis demonstrated a favorable safety profile for administration of the HuCNS-SC cells into the subretinal space of the study eye, according to the company.
Stephen Huhn, MD, FACS, FAAP, vice president, CNS clinical research and chief medical officer at StemCells, Inc., noted reasons why the company finds the interim data are encouraging. “First, the reduction in the rate of geographic atrophy suggests the HuCNS-SC cells are affecting the underlying cause of AMD. Secondly, the data demonstrate increases in contrast sensitivity, which is a vital aspect of visual function,” he said.
“These results are particularly interesting given that the first cohort of patients had significant visual impairment and baseline GA,” said David Birch, PhD., chief scientific and executive officer of the Retina Foundation of the Southwest in Dallas, TX.
■ Squalamine eyedrop data a mixed bag. The initial clinical data on a eyedrop therapy for wet AMD has been released and shows significant vision gains compared to placebo at nine months, but no meaningful reduction in the number of Lucentis (ranibizumab, Genentech) injections. A reduction in the need for ranibizumab injections was the primary endpoint while vision gains were a secondary endpoint.
Ohr Pharmaceutical (New York City) said that nine-month analysis of 29 patients receiving the squalamine aminosterol eyedrop plus Lucentis PRN and 33 patients receiving placebo and Lucentis PRN showed average vision gains of 10.9 letters for the squalamine group and 6.3 letters for the placebo group. However, the squalamine group required 6.2 Lucentis injections over nine months while the placebo group required 6.4 injections.
The squalamine-treated group demonstrated improved BCVA gains relative to the placebo group at all time points evaluated from four to 38 weeks. In the interim analysis group, 48.3% of squalamine-treated patients showed BCVA gains of 15 letters or more on a standard ETDRS eye-chart, compared with 21.2% in the placebo arm at the end of the study.
■ National commercial launch of RetnaGene AMD tests. Nicox, Inc., announced the commercial launch of Sequenom Laboratories’ RetnaGene portfolio of laboratory-developed genetic tests in the United States. The RetnaGene portfolio includes RetnaGene AMD and RetnaGene LR, specialized genetic tests that assess an individual’s risk for advanced age-related macular degeneration.
In January, Sequenom Laboratories granted Nicox exclusive promotion and marketing rights for its RetnaGene tests. Nicox has hired more field representatives to support the US launch.
■ AGTC raises $51.8 million in share offering. Applied Genetic Technologies Corporation (AGTC, Alachua, FL), a developer of investigational gene replacement therapies for retinal diseases, became a publicly traded company after a public offering that raised $51.8 million.
The company initially sold more than 4 million shares at an offering price of $12 a share. The stock has recently been trading around $30 a share.
AGTC is scheduled to begin human clinical trials in 2015 for three orphan retinal diseases: X-linked retinoschisis, achromatopsia and X-linked retinitis pigmentosa, all of which are rare diseases caused by mutations in single genes.
A Foreboding Outlook for Diabetic Eye Disease
Disease rates expected to triple, and half go untreated.
BY KAREN BLUM, CONTRIBUTING EDITOR
■ With rates of diabetic retinopathy estimated to triple by 2050, the medical community needs to increase diabetes patients’ awareness of potential vision loss and ensure they have their eyes examined at least once a year, experts said at an eye health meeting in June.
Currently, about 29 million people have diabetes, one in four of whom are unaware, said Jinan Saaddine, MD, MPH, Vision Health Initiative Team Leader for the Centers for Disease Control and Prevention. Half of people with diabetes do not receive annual eye examinations, she said at Prevent Blindness America’s Focus on Eye Health meeting.
Forty percent of those with diabetes have DR, said Neil Bressler, MD, chief of the retina division at the Wilmer Eye Institute at Johns Hopkins. But most do not seek eye care until their vision has worsened to between 20/60 and 20/100, he said, which can be compared to a moderate stroke in its impact on quality of life.
Type 2 diabetes now accounts for about 10% of diabetes in youth under age 20, which was “almost unheard of” before 2000, Dr. Bressler said. Although controlling blood-sugar levels and blood pressure can decrease the chance people will develop DME and other vision problems, fewer than half of youth under age 18 with type 1 diabetes use pumps, and only 5% use continuous glucose monitors, in part because they are cumbersome and expensive, he said.
Anti-VEGF injections to treat DME can provide substantial improvements for patients, but many are not aware they should pursue treatment, Dr. Bressler said. One of his studies using data from the National Health and Nutrition Examination Survey (NHANES) found that 55% of diabetes patients with DME and 73% of those with DR said they had not been told by a medical professional that diabetes had affected their eyes. Nearly 40% of those with DME and 32% of those with DR said their last comprehensive eye exam was more than a year ago or never.
Physicians should emphasize good control of blood sugar, blood pressure, and lipids, Dr. Saaddine said. They also should recognize that about half of people with diabetes and treatable eye disease may be under-utilizing the health care system, Dr. Bressler said.
Telemedicine could help increase diabetes patients’ access to eye care, Dr. Saaddine said, by putting fundus cameras in primary-care clinics.
A CDC-funded project, the Innovative Network for Sight Research, is studying the feasibility of fundus imaging in community-based primary-care clinics and an outpatient pharmacy to screen for DR and other eye diseases. Preliminary data suggest the technology can detect DR and other ocular conditions among people with diabetes who otherwise are hard to reach. Results will be submitted soon to a medical journal for publication.
■ Eylea Submitted for BRVO Approval in EU. Regeneron Pharmaceuticals and Bayer HealthCare have submitted an application to the European Medicines Agency seeking marketing authorization in the European Union for Eylea (aflibercept) injection for the treatment of macular edema following branch retinal vein occlusion (BRVO).
The EMA submission is based on the phase 3 VIBRANT trial, a double-masked, randomized, active-controlled study of patients with macular edema following BRVO. The study found 53% of patients who received Eylea 2 mg monthly gained at least 15 letters in BCVA from baseline at week 24, the primary study endpoint vs 27% of patients who received laser, a standard of care. Regeneron is awaiting a decision on a similar application filed with the FDA.
■ Genentech Receives Helen Keller Achievement Award. The American Foundation for the Blind (AFB) presented Genentech (South San Francisco, CA) with the award for its commitment to making health-care information accessible to patients and the public.
The company has supported AFB’s efforts to improve the accessibility of health-care websites, ensuring that people with vision loss can stay informed, and monitor and manage their medical treatment plans independently. Genentech has stated its commitment to ongoing research to advance delivery methods for its ophthalmic indications and to develop new treatments for other eye diseases RP.