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Phase 3 Brolucizumab Data Impress at AAO

Drug scores on key metrics in wet AMD study.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ In June, Novartis reported that initial 48-week data for its large-scale, phase 3 HAWK and HARRIER clinical trials of its anti-VEGF brolucizumab (RTH258) for wet AMD demonstrated a durable 12-week retreatment interval for a majority of patients in the 2 studies. The company released additional HAWK and HARRIER results at the recent AAO meeting in New Orleans, showing impressive efficacy in both eliminating retinal fluid and reducing central subfield thickness in a head-to-head comparison with aflibercept (Eylea; Regeneron).

Given this highly positive data, Novartis now plans to file for FDA approval of the wet AMD indication in late 2018 and begin clinical trials for DME and RVO in 2018 as well. It’s also possible that brolucizumab will be tried in combination therapy in the future and also in a sustained-release format.

Novartis describes brolucizumab as a humanized single-chain antibody fragment and the most clinically advanced, humanized single-chain antibody fragment to reach this stage of development. The company says single-chain antibody fragments offer the advantages of small size, enhanced tissue penetration, rapid clearance from systemic circulation, and versatility in drug delivery.

At week 48, relative to aflibercept, 31% fewer patients on brolucizumab 6 mg had intraretinal fluid and/or subretinal fluid in HAWK, and 41% fewer in HARRIER. Novartis said the absence of fluid for patients in the brolucizumab arm suggests the potential for a long-lasting effect and decreased treatment need. Additionally, brolucizumab 6 mg patients demonstrated superior reductions in central subfield thickness. Significantly improved CST reductions were evident in both HAWK and HARRIER at week 16 and at week 48.

Brolucizumab also met the primary efficacy endpoint of noninferiority to aflibercept in mean change in BCVA from baseline to week 48 in both trials. These results were achieved while a majority of brolucizumab patients — 57% in HAWK and 52% in HARRIER — were maintained on a 12-week dosing interval immediately following the loading phase through week 48. Brolucizumab is now the first anti-VEGF treatment for wet AMD to demonstrate robust visual gains with a majority of patients maintained on a less-frequent 12-week treatment interval immediately following the loading phase in randomized clinical trials.

“HAWK and HARRIER demonstrated that brolucizumab has the potential to positively impact disease management and provide long-lasting treatment effect,” said Pravin U. Dugel, MD, a vitreoretinal specialist with Retinal Consultants of Arizona in Phoenix and principal investigator of both trials. “HAWK and HARRIER showed that brolucizumab outperformed aflibercept on disease activity assessments, including key measures of disease progression seen on OCT, which forms the basis of a clinician’s treatment decisions,” Dr. Dugel told Retinal Physician.

“Importantly, improvements in these key OCT measures were seen as early as week 16 and maintained at week 48, with a majority of brolucizumab patients on a 12-week treatment interval,” he added. “This is the first prospective, randomized study to show that patients can be extended to 12 weeks; it’s a far higher level of data and scientific scrutiny than we’ve had with post hoc analyses and case studies. Importantly, the consistency of the data in the HAWK and HARRIER phase 3 studies as well as the OSPREY phase 2 study gives us confidence in the potential benefit of this drug.”

“Consistent data in a variable disease deserves emphasis,” he noted. “The preponderance of data points in the same direction, and that direction is the potential for better disease control,” he added. “If you have a drug that gives superior structural anatomic outcome, it suggests better disease control. It also could offer a more sustainable treatment strategy. The hope is that we can manage patients better and more sustainably.”

“Having delivered on our noninferiority endpoint with a majority of patients on a q12-week interval, we’re truly excited to share these data showing that brolucizumab clearly improves key anatomical outcomes that are biomarkers of disease,” said Vas Narasimhan, global head of drug development and chief medical officer for Novartis.

FDA Workshop Tackles Key Questions on Digital Ophthalmic Devices

Deep learning, mobile health hot topics at this panel event.

BY JENNIFER FORD, SENIOR MANAGING EDITOR

■ The 21st Century Cures Act clarified the FDA’s regulation of medical software, amending the definition of “device” in the Food, Drug and Cosmetic Act to exclude certain software functions. The FDA is currently developing draft guidance for public comment to help industry and FDA staff understand how the 21st Century Cures Act affects FDA’s oversight of medical device software (more information: https://www.fda.gov/medicaldevices/digitalhealth ).

To inform this initiative, the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH), along with 5 cosponsor organizations, hosted the first Ophthalmic Digital Health Workshop in October. Cosponsoring organizations were the American Academy of Ophthalmology (AAO), the American Academy of Pediatrics (AAP), the American Association for Pediatric Ophthalmology and Strabismus (AAPOS), the American Association of Cataract and Refractive Surgery (ASCRS), the American Society of Retina Specialists (ASRS), and Stanford University’s Byers Eye Institute.

Representatives from the FDA, various ophthalmology subspecialties, eye care industry, and health care informatics were present to share insights and to sit on panels discussing questions on the safety and effectiveness of a digital health device providing a diagnosis; the safety and effectiveness concerns for an ophthalmic digital health device used in various eye care or nonclinical environments; the most effective methods of mitigating risks for an ophthalmic digital health device; and the assets, threats, and vulnerabilities that should be considered and identified as a threat to the privacy of a patient by ophthalmic digital health device developers.

In his presentation on mobile medical devices and digital health, Zachary Bodnar, MD, ophthalmology innovation fellow and vitreoretinal fellow at Stanford University, stressed that when developing ophthalmology apps, there are many risk profiles to consider. Risk mitigation can include robust quality assurance and acknowledging the importance of user interface and user experience.

“The smartphone is ubiquitous,” he said, “It’s great for medical devices.” The smartphone brings technology to the point of care, improves efficiency and automation, streamlines communication, and provides insights with home monitoring, he added.

Discussion focused on improving image interpretation using deep learning and artificial intelligence (AI). An important concern for deep-learning and AI algorithms in ophthalmology is that results come from a “black box” that can’t be analyzed. But, said Michael Trese, MD, vitreoretinal specialist at the William Beaumont Hospital in Royal Oak, Michigan, “The black box is opening, and the gold standard is evolving.”

“This is a deep-learning revolution,” said Krishna Yeshwant, a physician, programmer, entrepreneur, and General Partner with Google Ventures. The modern reincarnation of artificial neural networks are much larger and more complex, he said, with the potential to read fundus images, perform small and large cohort analyses, and collect patient-generated data.

Telemedicine was an important part of the day’s conversation. R.V. Paul Chan, MD, a vitreoretinal specialist from the Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Illinois, discussed studies under way on telemedicine for ROP. The Imaging and Informatics in Retinopathy of Prematurity (i-ROP) and Global Education Network for Retinopathy of Prematurity (GEN-ROP) groups are developing a telecertification program to help physicians identify missed ROP diagnoses and improve their accuracy.

More home-based testing could soon be a reality, evidenced by a presentation by Quinton Oswald, CEO of Notal Vision, in which he described the company’s home-based OCT telemonitoring application, the Notal Home OCT. The system, according to Oswald, uses AI to automate analysis of home-based OCT output and identifies fluid and lesion activity. In preliminary studies, compared to reading center and independent retinal specialists, home OCT had the same reliability.

The ultimate goal of digital ophthalmology initiatives, as generally agreed upon by attendees, is to thoroughly assess risk and to create devices, apps, systems, and algorithms that keep data safe. Clinicians will continue to provide the context that enables accurate analysis of data. Apps must be integrated across channels so that patients can easily use them. Physicians, industry, and regulators must train a keen eye on these considerations and collaborate to create successful systems that improve care. Unanswered questions remain about who owns any data collected and how to safely store data.

Presentation slides and a transcript will be available at http://www.cfom.info/meetings/OphthalmicDigitalHealth/Agenda%20_Registration.html .

Aura Has Initial Data on Eye Cancer Therapy

Stable disease and vision after 3 months.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ Aura Biosciences said the first 6 patients treated with its novel, light-activated AU-011 therapy for primary ocular melanoma had stable disease and vision at 3 months following treatment in a phase 1b/2 clinical trial. Based on the discoveries of John T. Schiller, PhD, at the National Cancer Institute, the 12-patient, phase 1 safety study of AU-011 employs intravitreally delivered viral nanoparticles modeled on the human papilloma virus. These nanoparticles are a vehicle for potent cytotoxic therapies that can selectively eliminate cancer cells following laser activation. In addition, AU-011 was granted orphan drug status for ocular melanoma by the FDA in 2015.

Depending on how early the disease is diagnosed, people afflicted with ocular melanoma have faced either radiation therapy or surgery that often includes enucleation. If not caught at an early stage, ocular melanoma usually metastasizes to the liver, where it is generally fatal. AU-011 is designed to shrink and then eliminate the cancer with a single course of treatment, though retreatment may be needed for some larger tumors.

“There has not been a new drug in 50 years; that’s the desert we face,” Aura Biosciences CEO Elisabet de los Pinos, PhD, told Retinal Physician. “We don’t often have this opportunity, and we want retina specialists to pay attention to this disease early because they are the ones who make the difference.”

Interim data presented at the recent AAO meeting in New Orleans show that the drug therapy was generally well tolerated, with no serious adverse events reported, in the first 6 patients at 3 to 6 months post treatment with AU-011. All patients maintained visual acuity. The preliminary efficacy measurement of tumor thickness on B-scan ultrasound at 3 months post treatment showed that all patients had stable disease, and only 1 patient experienced tumor progression at 5 months.

“These preliminary findings are an encouraging step forward in our effort to evaluate the potential of AU-011 for the treatment of ocular melanoma,” said Carol Shields, MD, who presented the findings at the AAO meeting. “Today, there are no treatment options available for patients that can effectively target tumor cells while still preserving vision. We are excited to build on these initial results as this important research progresses.”

Preclinical data on evaluation in animal models were published in December in Molecular Cancer Therapeutics.

New Guidelines for Eye Cancer Screening

The result of a 2-year team effort.

■ The first US guidelines on conducting early screening for retinoblastoma, the most common eye tumor affecting children, are now available. The guidelines, which cover both hereditary and nonhereditary eye cancer, were recently published online in Ophthalmology.

Children with hereditary retinoblastoma often develop retinal tumors in both eyes within the first years of life. Early diagnosis, when tumors are small, improves the child’s chance of survival and their chance of keeping their vision and their eyes.

The guideline initiative was spearheaded by ophthalmologist Alison Skalet, MD, PhD, of the Casey Eye Institute in Portland, Oregon. Dr. Skalet and Patricia Chévez-Barrios, MD, an ophthalmologist and pathologist from Houston Methodist Hospital, led a team of ophthalmologists, pathologists, and geneticists to devise the guidelines.

The guidelines address a knowledge gap among ophthalmologists and other health care professionals regarding risk for inherited retinoblastoma and best practices for screening examinations. Dr. Chévez-Barrios said the new guidelines meet the team’s goal to focus care on children at the highest risk for disease while decreasing unnecessary examinations for children at lower or no risk of developing retinoblastoma.

Ophthalmologists say there are signs to look for that may indicate retinoblastoma. They include a white color in the pupil when a light is shone in the eye, such as when taking a flash photograph. Also, eyes that appear to be looking in different directions could be a sign of trouble. They encourage parents to make an appointment with their child’s pediatrician if they notice any changes to their child’s eyes.

Eylea/Ang2 Combo Disappoints in Phase 2

Regeneron discontinues further development.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ A Regeneron combination therapy that the company had previously deemed as highly promising has failed in phase 2 trials. Regeneron said results from two phase 2 studies that added the angiopoietin2 (Ang2) antibody nesvacumab to the anti-VEGF Eylea (aflibercept; Regeneron) injection did not provide sufficient differentiation to warrant phase 3 development. The RUBY study evaluated patients with DME and the ONYX study evaluated patients with wet AMD. Eylea results were consistent with findings in previous clinical studies. There were no new safety signals in these studies.

“We knew from the start that it would be difficult to improve on the already high bar set by Eylea, which is the market-leading branded therapy in its approved indications,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer, Regeneron. “We expect to report results in the first half of 2018 from our phase 3 study in DR.”

RUBY and ONYX were randomized, double-masked, active-controlled phase 2 studies that investigated if a combination of aflibercept and nesvacumab offered additional benefit over aflibercept monotherapy. The studies evaluated two doses of nesvacumab in combination with aflibercept, both administered as a single coformulated intravitreal injection, as well as aflibercept monotherapy. The primary endpoint for both trials was change in BCVA between weeks 12 and 36 as measured by the ETDRS letter score.

Genentech and Aerpio are also conducting clinical trials that include an Ang2 component, but Pravin Dugel, MD, of Retinal Consultants of Arizona, cautioned that no conclusions should be drawn on these studies based on the Regeneron data. “The other two drugs have different mechanisms of action,” said Dr. Dugel.

The failure of Regeneron’s ONYX and RUBY trials is a disappointment to retina specialists hoping to expand on the efficacy of anti-VEGF therapeutics, said Paul A. Yates, MD, PhD, associate professor of ophthalmology at the University of Virginia.

“Dual targeting of Ang2 and VEGF is a rational approach,” said Dr. Yates. “One also cannot rule out that the specific formulation of Ang2 and VEGF inhibition might matter, given the favorable phase I results reported for Roche’s Ang2/VEGF bispecific antibody,” he added.

Aqueous Humor Biopsy for Retinoblastoma

New methods could facilitate diagnosis for children with retinoblastoma.

■ A study by a team of researchers at the Vision Center of Children’s Hospital Los Angeles (CHLA) and the University of Southern California (USC) Roski Eye Institute provides proof of concept for a safe and effective way to derive genetic information from retinoblastoma tumors. Results of the study were recently published in JAMA Ophthalmology.

In treating the small particles or “seeds” that break off from the main tumor, ocular oncologists now inject chemotherapy directly into the eye. As part of this procedure, it is first necessary to remove a small amount of aqueous humor from the front of the eye to decrease the pressure within the eye prior to injection of the medication. The study reported on 6 samples from 3 eyes affected with retinoblastoma, in children younger than 3 years of age. Aqueous humor was taken from all 3 eyes and allowed investigators to compare tumor DNA in the aqueous humor to DNA found in the retinoblastoma tumor.

“The most exciting aspect of this research is to finally have access to retinoblastoma tumor DNA in eyes that have not been enucleated,” said Jesse Berry, MD, ocular oncologist at CHLA, assistant professor of clinical ophthalmology at the USC Roski Eye Institute, and first author on the study. “While we know a significant amount of the genetic underpinning of this cancer we have never before been able to harness it without removing the eye. This paper, while early research, demonstrates that the aqueous humor hold tremendous potential to serve as a surrogate tumor biopsy which is the first step towards precision medicine for children suffering from this blinding — and deadly — ocular cancer.”

The team of investigators plans future studies to compare tumor DNA from eyes that have been saved to those that need to be removed due to tumor recurrence.

IN BRIEF

Research and industry news in retina.

BY JERRY HELZNER, CONTRIBUTING EDITOR

FDA approves Spark gene therapy for IRD

■ In a somewhat unexpected December announcement, the FDA has approved Spark Therapeutics’ one-time Luxturna (voretigene neparvovec) gene therapy for treating children and adults with progressively blinding inherited retinal dystrophies. Though approval was not expected until January, it was considered to be something of a formality following a unanimous 16-0 vote by an FDA advisory panel in October. Luxturna is the first-ever gene therapy for a genetic disease to be approved in the United States.

Key to the FDA approval was the pivotal phase 3 trial that met its primary endpoint of improvement of functional vision in a 20-patient intervention group compared to a 9-patient control group, as measured by the change in bilateral mobility testing between baseline and 1 year. All patients in the control group then opted for intervention and 8 of those individuals also responded positively to treatment. Patients who received the therapy were successful in navigating a marked path in dim light, something they could not do at baseline testing. There were no serious adverse events reported.

JCyte reports promising RP trial

■ Cell therapy company jCyte reported encouraging results from a 28-patient, phase 1/2a clinical trial for its investigational product, jCell, in retinitis pigmentosa (RP). The 12-month study showed a favorable safety profile and indications of potential benefit. jCell has been granted both Orphan Drug and Regenerative Medicine Advanced Therapy designations by the FDA.

In this treatment, retinal progenitor cells are injected into the vitreous cavity of the eye under topical anesthesia. The hope is to rescue and reactivate diseased photoreceptors before they die.

To evaluate changes in visual acuity, the study assessed mean difference in BCVA change between treated and untreated eyes at specified time points throughout the study. In the lowest dose group (500,000 cells), the mean difference was 1 letter at 12 months after treatment, while at the highest dose (3 million cells), the mean difference was 9 letters. The company says the FDA has encouraged JCyte to explore higher doses. Observed side effects were generally minor, transitory, and consistent with an intraocular injection.

OCT testing saving Medicare billions

■ A $400 million investment by the federal government in OCT over 20 years has produced $9 billion in Medicare savings through the use of OCT testing to determine when anti-VEGF retreatments for retinal disease are needed.

A study whose coauthors include OCT pioneers David Huang, MD, PhD, FARVO, Eric Swanson, and Philip Rosenfeld, MD, PhD, published in the American Journal of Ophthalmology, details the major role now played by OCT in guiding retina specialists in making their retreatment decisions. OCT is key in measuring such critical metrics as subfield central subfield thickness and the presence or absence of intraretinal and subretinal fluid.

“Our paper is a rare example of being able to quantify the impact research can have, in this case via reduced healthcare spending. We have shown that return on research investment can be very high,” says Dr. Huang, professor of ophthalmology at the Casey Eye Institute.

FDA to review 12-week Eylea dosing

■ The FDA has agreed to review Regeneron’s submission of a supplemental Biologics License Application for 12-week dosing of Eylea (aflibercept) for wet AMD based on the treating physician’s assessment. The current Eylea label calls for every-8-week dosing following 3 initial monthly loading doses.

The decision came after integrated data from the VIEW 1 and VIEW 2 clinical trials showed that 51% of the patients receiving Eylea for wet AMD could be successfully retreated at 12-week intervals in the second year of the trial. The FDA review is expected to be completed by August 11, 2018.

News of the Eylea review follows recent news that the investigational anti-VEGF brolucizumab (Novartis) demonstrated successful 12-week retreatment intervals for the majority of wet AMD patients in the pivotal HAWK and HARRIER phase 3 trials.

LumiThera pursues light therapy for dry AMD

■ LumiThera is currently conducting the 30-patient LIGHTSITE I clinical trial for dry AMD using noninvasive low-level light therapy (LLLT) to stimulate photoreceptor cells in the retina and return them to normal function. In a previous 24-patient study LumiThera reported at ARVO 2016, a 3-week application of LLLT, also known as photobiomodulation, produced a gain of almost 6 letters, which was largely maintained 3 months after treatment.

The study also resulted in reduced drusen volume and improved contrast sensitivity. These results were essentially replicated in interim three-month data recently released from the LIGHTSITE I study, with the most promising results in patients with better baseline vision. Patients in LIGHTSITE I will undergo another treatment cycle at the 6-month interval.

The company’s stated goal is to develop and obtain regulatory approvals for its LT-300 device that will be used to apply light-emitting diode (LED) treatments in an office setting. LumiThera also recently obtained an additional $5.5 million in Series B financing to further international development of its technology.

Second Sight gets favorable rulings

■ Second Sight Medical, a developer of implantable visual prosthetics to provide useful vision to patients with extreme vision loss, said the company has received FDA approval to begin a 5-patient study of its next-generation Orion device, which connects directly with the visual cortex of the brain. The cortical connection opens the door to bringing a level of functional vision to patients afflicted with virtually any type of blindness.

In addition, the FDA has given the Orion an “expedited access pathway” to approval, which is the device equivalent of “breakthrough status.” The designation essentially means that the Orion can be approved with fewer clinical trial patients and with a shorter follow-up timeline, potentially allowing quicker access to the commercial marketplace.

In Germany, approval by regulatory authorities, and a favorable opinion by the applicable ethics committees, will allow Second Sight to begin a 10-patient study to implant and evaluate the Argus II Retinal Prosthesis System in better-sighted retinitis pigmentosa (RP) patients, or those individuals who have some “tunnel vision.” Tunnel vision is a condition defined by a visual field that is severely constricted.

“If successful, the targeted population could increase the potential market for the Argus II by 2 to 3 times its current size,” said Will McGuire, president and CEO of Second Sight.

The Argus II has been approved by the FDA and in numerous countries internationally to provide a level of functional vision to individuals with end-stage RP.

Antria Bio to advance oral DME therapy

■ Antria Bio plans to move an oral therapy for DME from its oral plasma kallikrein inhibitor (PKI) portfolio into a clinical trial. The drug, known as AB402, is for vision-threatening eye complications of diabetes, including diabetic retinopathy and DME.

“Despite recent advances in the treatment of diabetic retinopathy, we need new therapies to better control this disease via alternative molecular pathways and a noninvasive drug delivery route that allows for self-administration by patients,” stated Robert Bhisitkul, MD, professor of clinical ophthalmology at the University of California, San Francisco School of Medicine. “The oral plasma kallikrein inhibitors hold promise for enhancing diabetic retinopathy management and improving vision outcomes for millions of patients in the US and worldwide.”

The company is advancing AB402 toward clinical trials and plans to file an investigational new drug application for the DME indication in Q4 2018.

Pursuant Health kiosks to offer DR screenings

■ Pursuant Health, which currently offers a range of health risk assessments through its network of more than 3,6000 self-service kiosks, said it is negotiating the first 10 to 20 locations that will provide screening using retinal imaging for signs of diabetic retinopathy. The screens will be evaluated by eye specialists and reported back to primary care physicians, the company said.

Pursuant said the DR screening locations will be at retail pharmacies and health care providers and will provide convenient retinal disease screening for the 50% of diabetics and others who don’t get regular examinations.

Retina doctors spearhead breakthrough IOL

■ Two retina specialists, Daniel Schwartz, MD, and Ron Kurtz, MD, have been instrumental in the recent FDA approval of the RxSight Light Adjustable IOL, a breakthrough lens that can be adjusted through a chemical reaction to optimize vision following implantation. Dr. Schwartz co-founded the company originally as Calhoun Vision and Dr. Kurtz serves as president and CEO.

Implementing the light-adjustable concept was achieved with the help of a Nobel laureate in chemistry from Caltech and an expert in chemical engineering, also from Caltech. Scientists from the University of California San Francisco also played key roles in the development of the lens. Both Caltech and UCSF provided financial resources for the research.

Apellis Pharmaceutical sells stock to public

■ Apellis Pharmaceutical has completed a successful public offering of 10.7 million shares of common stock at $14 a share, raising approximately $150 million before discounts, commissions, and expenses. Apellis recently reported positive data for its complement inhibitor APL-2 in slowing progression of geographic atrophy in its phase 2 FILLY trial.

New Topcon laser approved

■ Topcon Medical Systems, Inc. said its Pascal Synthesis TwinStar laser (combined 577 nm and 638 nm) has received FDA 510(k) clearance. The Synthesis TwinStar further expands the Pascal line of laser photocoagulators offering the ability to treat retinal disorders with a 577 nm yellow wavelength or with a 638 nm red wavelength.

The yellow module allows doctors to treat with a single spot as well as with a variety of patterns and four spot sizes. The yellow module can also be used with the optional Endpoint Management software for subthreshold procedures. The red wavelength, effective for targeting choroidal vessels in the neovascular membrane, is for single-spot treatments and has 2 different spot sizes.

DigiSight, Notal Vision in IRIS Registry collaborations

■ The American Academy of Ophthalmology and DigiSight Technologies will collaborate to operate the world’s largest database of ophthalmic clinical information. As part of the agreement, the AAO is licensing commercial application of its IRIS Registry (Intelligent Research in Sight) to DigiSight. Terms were not disclosed. The arrangement enables DigiSight to build new analytic applications and user interfaces to enhance the IRIS Registry, which will be marketed to pharmaceutical companies, device manufacturers, health systems, payers, and other customers that can benefit from the database to innovate ophthalmic patient care.

In other IRIS news, Notal Vision, Ltd., a privately held ophthalmic company focused on a cloud-based platform for remote diagnostic testing, has entered a collaboration with the AAO to use IRIS to better understand real-world visual acuity (VA) in patients with AMD.

Landmark clinical studies of anti-VEGF therapy for AMD have demonstrated that the best predictor of visual outcomes is baseline VA. Absolute vision remains significantly better over time in patients that have a better VA at diagnosis and treatment initiation. To better understand this predictor and characterize VA, Notal will evaluate data from the IRIS Registry on VA at the time of AMD diagnosis across all eyes, as well as the first eye and second eye to convert. Additional analyses will examine relationships between VA at diagnosis and longer-term treatment outcomes and number of injections required.

The IRIS Registry was developed to improve patient care, enable clinical discovery, and simplify federal government and commercial payer quality reporting. It is a centralized collection and analytic software tool that compiles and processes data from electronic health records and other sources to enable ophthalmologists to analyze patient outcomes, benchmark to their peers, and pinpoint opportunities for improvement. Launched in 2014, it is the largest specialty based clinical data registry in all of medicine, with more than 41.2 million unique patients in its database, representing 166.2 million patient visits.

Angiogenesis Foundation offers “white paper” on wet AMD

■ The Angiogenesis Foundation, in consultation with leading retina specialists and patient advocates, has produced a white paper intended to achieve better patient outcomes for wet AMD. The paper is titled Improving Long-Term Patient Outcomes for Exudative Age-Related Macular Degeneration. It is available online at www.angio.org under the “Advocacy” heading at “White Paper Reports.”

Recommendations in the white paper include promoting AMD awareness in the general population, developing evidence-based treatment guidelines, promoting the use of home-monitoring for early detection of wet AMD, addressing undertreatment in the clinical setting, encouraging treatment of the “whole patient” including offering access to low-vision support services, and developing a real-world, late-stage research agenda for the treatment of exudative AMD.

Lampalizumab fails second phase 3 trial

■ Genentech said its complement inhibitor lampalizumab failed its second phase 3 trial for geographic atrophy with results similar to the disappointing results released for the first phase 3 trial in September. The intravitreal drug was unable to meet its primary endpoint of reducing the mean change in lesion area at 1 year. The company said it would not pursue the GA indication for lampalizumab.

Oral therapy for Stargardt gets orphan status

■ Lin BioScience said the FDA has granted orphan drug status to LBS-008, a first-in-class oral therapy for the treatment of Stargardt disease. Stargardt disease is caused by a mutation in the ABCA4 gene, leading to the accelerated formation and accumulation of toxic vitamin A dimers in the retina that cause progressive retinal cell death and permanent loss of vision.

LBS-008 acts to prevent the buildup of toxins in the eye that cause Stargardt Disease and dry AMD. The toxins are a byproduct of the eye’s visual cycle, which is dependent on presence of vitamin A1 (retinol).

LBS-008 works by reducing both the amount of circulating retinol binding protein and retinol, thus reducing its excess uptake into the eye and preventing the formation of the toxins associated with macular degeneration. The NIH Blueprint Neurotherapeutics Network, which has funded the therapy’s discovery and development, will continue to provide support and funding through to the completion of phase 1 clinical trials.

Slow recruitment stymies study

■ ThromboGenics has discontinued patient recruitment in its phase 2 CIRCLE study for nonproliferative diabetic retinopathy (NPDR) due to the trial’s slow recruitment rate. CIRCLE was to evaluate the safety and efficacy of up to 3 intravitreal injections of ocriplasmin to induce complete posterior vitreous detachment (total PVD) in NPDR patients, potentially avoiding disease progression from NPDR to the more serious proliferative DR.

Because early symptoms of NPDR do not immediately affect a patient’s vision, many potential patients for this study have experienced few symptoms and therefore are less aware of their disease. ThromboGenics believes these factors contributed to the slow recruitment rate and led to the decision to discontinue enrollment. Ocriplasmin was found to be generally safe and well tolerated with no new safety signals raised.