SUBSPECIALTY NEWS

Younger Patients Do Well With IMT

Approval for 65 to 74 age group validated.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ VisionCare Ophthalmic Technologies, Inc. (Saratoga, CA), a developer of advanced visual prosthetic devices for the treatment of AMD, said newly published five-year data in the journal Clinical Ophthalmology show substantial retention of gains in visual acuity over time after implantation with the Implantable Miniature Telescope (IMT).

The study reported that both younger (aged 65 to <75) and older patients (aged 75+) had clinically significant visual acuity gains at two years as well as five years after telescope implantation. Younger patients retained more of the vision gains at five years and experienced somewhat fewer adverse events.

The data from this long-term study supported a labeling indications expansion request that resulted in an October 2014 FDA approval to include patients between the ages of 65 and 74, in addition to those 75 and older. The telescope implant is the only FDA-approved, Medicare-eligible surgical device to treat the most advanced form of AMD. “These data demonstrate that the telescope implant is a clinically meaningful treatment option for patients with cataracts who have bilateral age-related macular degeneration associated with central vision loss,” stated David S. Boyer, MD, vitreoretinal specialist at Retina-Vitreous Associates Medical Group in Beverly Hills, CA and lead author. “The fact that these 65- to 74-year-old patients, on average, retained nearly 3 lines of improvement five years after telescope implantation is tremendous.”

RetroSense Plans Gene Therapy Trial in RP

Therapy is based on optogenetics concept.

■ RetroSense Therapeutics, LLC (Ann Arbor, MI), a privately held biopharmaceutical company, said the company’s Investigational New Drug (IND) application for its RST-001 received clearance from the FDA for the treatment of retinitis pigmentosa (RP). With its IND now in effect, RetroSense expects to initiate a phase 1/2 clinical trial by year-end in order to evaluate the safety and, potentially, efficacy of RST-001.

RetroSense is developing RST-001 as a first-in-class gene therapy application of optogenetics. Optogenetics refers broadly to means of conferring light sensitivity to cells that were not previously, or natively, light sensitive. By applying optogenetics to retinas in which rod and cone photoreceptors have degenerated, RetroSense is working to confer new light sensitivity to the retina, with the expectation of some degree of improved or restored vision for affected patients. The basic research for the RetroSense concept has been conducted at Wayne State University and Massachusetts General Hospital.

In 2014, the FDA granted Orphan Drug designation for RST-001 based on its development as a treatment of RP. As an Orphan Drug, RST-001 is eligible for various development incentives under the Orphan Drug Act.

“The IND for RST-001 is an important milestone for the company. This brings us one step closer to realizing our ambition of improving vision in those individuals with currently incurable blindness,” said Sean Ainsworth, CEO of RetroSense Therapeutics. “There is great promise for the clinical application of optogenetics and this first human clinical trial should provide key insights into the potential for this therapy to treat diseases affecting the eye or brain.”

Are We Screening Too Early for DR?

New study recommends later age for children.

■ A new study has found that the occurrence of diabetic retinopathy remains low among children living with diabetes, regardless of how long they have had the disease or their ability to keep blood sugar levels controlled. Researchers are therefore recommending that most children with type 1 diabetes delay annual diabetic retinopathy screenings until age 15 or five years after their diabetes diagnosis, whichever occurs later. Their findings were published online recently by the journal Ophthalmology.

It is well established that early detection and timely treatment of diabetic retinopathy reduces vision loss in adults, and some physician organizations recommend screening children for diabetic retinopathy annually starting at an early age — after age nine, or from three to five years after diagnosis. However, the researchers contend that the value of screening children has not been clearly documented and the prevalence of severe diabetic retinopathy among the young has been unclear.

Researchers based at The Children’s Hospital of Philadelphia (CHOP) and the Scheie Eye Institute at the University of Pennsylvania began to question current diabetic retinopathy screening guidelines for children. They were concerned that these annual exams may create an excessive financial and logistical burden for families and the health care system.

The researchers conducted a retrospective study of 370 children under age 18 with type 1 and type 2 diabetes, some with extremely high blood sugar levels. All had received at least one diabetic eye disease screening exam between 2009 and 2013, but none was found to have diabetic retinopathy.

The researchers then examined the data that led to the current screening guidelines. They discovered that previous studies reported a diabetic retinopathy prevalence rate between 0% and 28% among children studied, but the majority of the cases were very mild and thus would not qualify for treatment. They also found that the youngest person reported to have severe diabetic retinopathy was between 15 and 19 years old, and cited research showing that five to six years was the shortest reported duration of having diabetes before developing severe diabetic retinopathy.

In light of the available evidence, the researchers recommend that screenings for children with type 1 diabetes could begin at a later age than previously recommended.

“Many of our young patients with diabetes diligently come in every year for screenings that consistently show no sign of the disease,” said Gil Binenbaum, MD, MSCE, coauthor of the study and attending surgeon in the ophthalmology division at CHOP. “Of course, that’s good news for them, and it is very important to have annual eye exams once the risk of vision loss develops. But, is it worth the burden on the family and the healthcare system if evidence shows that diabetic retinopathy doesn’t reach a treatable stage until years later?”

Researchers say exceptions should be made for children with type 2 diabetes and those identified as having high risk for diabetic complications. They should start diabetic retinopathy screenings upon diagnosis, similar to adults with type 2 diabetes, since many type 2 diabetes patients live with the disease uncontrolled before they are diagnosed.

Because there is limited published research on children with type 2 diabetes and diabetic retinopathy, researchers noted that a retinopathy screening examination upon diagnosis is their recommendation for those patients until additional data showing otherwise are available.

AGTC Opens New Facility in Cambridge, MA

“World’s premier” life sciences location

■ AGTC, a biotech company conducting human clinical trials of adenoassociated virus (AAV)-based gene therapies for the treatment of rare eye diseases, has announced the opening of a new office facility in the biotech hub of Cambridge, MA.

The office is a second US location to the company’s headquarters in Gainesville, FL. The new location in Cambridge, consisting of office and laboratory space, will focus on business development, pharmacology, and basic R&D.

“Following our recently announced collaboration with (Cambridge-based) Biogen as well as the appointment of our two Cambridge-based officers, Stephen Potter, CBO, and Mark Shearman, CSO, we recognized the need to have a presence in Cambridge as it has become the world’s premier life sciences cluster,” said Sue Washer, CEO of AGTC. “With close proximity to leading life science and medical innovators, world-class academic research centers and a deep talent pool, having a presence in Cambridge will be beneficial to fostering AGTC’s ongoing business and clinical development activities.”

AGTC has a robust product pipeline, including five named ophthalmology development programs across four targets (XLRS, XLRP, achromatopsia and wet AMD), one non-ophthalmology program (alpha-1 antitrypsin deficiency), and proof-of-concept data in multiple additional indications. The company employs a highly targeted approach to selecting and designing its product candidates, choosing to develop therapies for indications having high unmet medical need, clinical feasibility, and commercial potential. The company also has a significant intellectual property portfolio and expertise in the design of gene therapy products, including capsids, promoters, and expression cassettes, as well as expertise in the formulation and physical delivery of gene therapy products.

Promising IRay Results Reported at EURETINA

Data presented in three parts in Nice, France.

BY LAIRD HARRISON

■ Patients treated with stereotactic radiation therapy (IRay, Oraya Therapeutics, Newark, CA) for neovascular AMD need fewer injections and may have better visual acuity, according to researchers who presented their findings at the European Society of Retina Specialists’ 15th EURETINA Congress in Nice, France.

“Oraya therapy results in superior vision in an environment of probable undertreatment while at the same time reducing the injection burden,” said Christopher Brand, FRCOphth, of Sheffield Teaching Hospitals in Sheffield, United Kingdom.

Dr. Brand’s report was one of three at this meeting to report on patients who have been treated with the new therapy for AMD. Less positive results for polypoidal choroidal vasculopathy were also presented.

Although anti-VEGF drugs can help most patients with neovascular AMD, the large number of injections typically required is costly and tiring for patients. So researchers have been looking for alternative and supplementary treatments.

IRay delivers 24 Gy of x-rays to the fovea via the inferior pars plana in three overlapping beams. Its uses a disposable contact lens to stabilize the eye, and its automated positioning system reduces the risk of scatter to surrounding tissues. Treatment lasts about 15 minutes.

In an electronic poster at this meeting, Dr. Brand presented the results in 58 treatment-naïve patients six months after they began treatment with ranibizumab (Lucentis, Genentech, South San Francisco, CA) in combination with this stereotactic radiation therapy. At a satellite symposium sponsored by Oraya, Dr. Brand elaborated on the 58 patients, and also described 12-month results in 25 patients as compared to patients who received ranibizumab alone.

The stereotactic radiation patients first received a loading injection of ranibizumab, then stereotactic radiation with IRay within 14 days. After two more loading doses of ranibizumab, they received further injections of the drug as needed (PRN).

The 58 patients followed for six months improved by an average of four letters, and those followed to 12 months gained an average of 1 more letter, for a total of 5. The comparator group meanwhile gained only one letter at six months, then lost visual acuity after that, ending up after 12 months with an average loss of 0.3 letters compared to baseline.

The combined therapy group, needed an average of 4.6 injections, compared to 5.63 for the comparator group. The researchers did not find any microvascular changes indicating harm from the radiation. “We would not perhaps expect them at 12 months,” Dr. Brand said.

Two other researchers at the satellite symposium also presented their experiences in which the stereotactic therapy appeared to reduce the need for injections in patients who had already received multiple anti-VEGF injections after 12 months. Visual acuity was stable in these patients.

Not all the results reported at the meeting were as stellar, however. As a treatment for polypoidal choroidal vasculopathy, stereotactic radiotherapy looks a little less promising, reported Ugo Introini of the Scientific Institute San Raffaele, University Vita-Salute in Milan, Italy, in a scientific “free paper” session at the meeting.

Following one 0.5-mg dose of ranibizumab, 12 patients followed by Dr. Introini and his colleagues received stereotactic radiotherapy between one and 14 days later.

Twelve months after that, angiographic regression of the polyps could be seen in 10 out of 12 eyes. But at 24 months, only five eyes had maintained this regression. The polyps had recurred in four and apparently spread to a new area of one eye. The two eyes that had not improved at 12 months still did not improve at 24 months.

Visual acuity followed this pattern as well, improving from 65.09 letters at baseline to 72.7 letters at month 12, then dropping back to 66.92 letters at month 24.

The mean number of intravitreal ranibizumab injections was 3.9 in the first year and 3.58 in the second.

As for adverse events, two eyes showed signs of microvascular abnormalities at 12 months, possibly as a result of the radiation. But these abnormalities never exceeded two disc areas, and they resolved spontaneously by month 24.

“Additional research is warranted to evaluate retreatment strategy and to confirm efficacy and longer-term safety in this population,” Dr. Introini concluded. RP