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SUBSPECIALTY NEWS: Coronavirus impact on industry, clinical trials, and retina practice.

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Second Sight Winding Down Operations

Company will hire an outside adviser for next steps.

■ Second Sight Medical Products, a developer, manufacturer, and marketer of implantable visual prosthetics that are intended to create an artificial form of useful vision for blind individuals, including the FDA-approved Argus 2, announced that in response to the impact of the global coronavirus pandemic on its ability to secure financing, the company has laid off approximately 84 of its 108 employees. The board of directors has evaluated strategic alternatives and decided to pursue an orderly wind down of the company’s operations. The company intends to retain an adviser to guide the board on next steps. Additional layoffs are expected to be made at a later date based on the company’s level of operations.

With more than 20 years of experience in neuromodulation for vision and numerous patents, Second Sight’s chief asset is the investigational Orion Visual Cortical Prosthesis System (Orion), an implanted cortical stimulation device intended to provide useful artificial vision to individuals who are blind due to a wide range of causes, including glaucoma, diabetic retinopathy, optic nerve injury or disease, and eye injury. Orion is intended to convert images captured by a miniature video camera mounted on glasses into a series of small electrical pulses. The device is designed to bypass diseased or injured eye anatomy and to transmit these electrical pulses wirelessly to an array of electrodes implanted on the surface of the brain’s visual cortex, where it is intended to provide the perception of patterns of light. A 6-subject early feasibility study of the Orion is currently under way at the Ronald Reagan UCLA Medical Center in Los Angeles and the Baylor College of Medicine in Houston. No peer-reviewed data are available yet for the Orion system.

Coronavirus Delays Pivotal Retinal Trials

Iveric bio and ProQR announce pauses.

■ Both Iveric bio and ProQR have paused pivotal trials for retinal disease because of the coronavirus outbreak. Iveric bio has decided to delay the initiation of enrollment of patients in the second pivotal clinical trial for Zimura (avacincaptad pegol), a novel complement C5 inhibitor, in development for the treatment of geographic atrophy secondary to dry AMD.

“In light of the COVID-19 pandemic and out of an abundance of caution for the safety and well-being of our elderly patients and participating physicians and their staffs, we have decided to delay the initiation of enrollment in our second pivotal trial of Zimura in geographic atrophy secondary to dry AMD, the ISEE2008 trial, which was on track to begin this month,” stated Glenn P. Sblendorio, CEO and president of Iveric bio, in a news release. “It is critically important that we heed the warnings from the US Centers for Disease Control, World Health Organization, and national, state, and local governments during this time of uncertainty. We will continue to closely monitor the situation in the United States and abroad to determine when enrollment should begin.”

In addition, ProQR is pausing all of its clinical trials, including those for Usher syndrome, Leber congenital amaurosis 10, and autosomal-dominant retinitis pigmentosa. This includes the ILLUMINATE pivotal trial of sepofarsen for Leber congenital amaurosis 10. ProQR is implementing mitigation procedures that support a rapid ramp-up in enrollment as soon as the disruption resolves, including additional patient identification activities and documentation for additional site activations, while prioritizing the safety of trial participants and health care providers. For the trials of QR-421a (Usher syndrome) and QR-1123 (autosomal-dominant retinitis pigmentosa), patients have already been identified for the next dose cohorts, and the company expects to begin dosing as soon as practical after clinical sites are ready and able to do so. The company currently does not believe that its supply chain will be affected. The ProQR pipeline focuses on severe eye diseases that have limited treatment options. All of the medicines are RNA therapies and target the underlying cause in the diseases.

Editor’s note: See “Targeting RNA for Retinal Disease” on page 24 for more on RNA-based gene therapy.

Pravin U. Dugel, MD, Joins Iveric bio in Senior Post

Dr. Dugel sees promise for Zimura in geographic atrophy.

■ Iveric bio has named Pravin U. Dugel, MD, as executive vice president and chief strategy and business officer. In this role, Dr. Dugel will help shape Iveric bio’s business development strategy. Dr. Dugel brings more than 25 years’ experience in the treatment of retinal diseases. He will report to CEO and President Glenn P. Sblendorio. Iveric bio also recently announced that the US Food and Drug Administration (FDA) granted fast track designation to avacincaptad pegol (Zimura), a novel complement C5 inhibitor, for development for the treatment of geographic atrophy (GA) secondary to dry AMD. Currently, there is no approved treatment option available for patients with GA secondary to dry AMD.

“I wanted the opportunity to join a company in which I could have direct input on the business strategy on a number of important assets, from GA to gene therapy,” Dr. Dugel told Retinal Physician. “The fact that the first part of the Zimura phase 3 registration studies have already been positively completed is very attractive.

“I am particularly excited about Zimura’s potential to positively impact and transform the lives of patients with geographic atrophy secondary to dry age-related macular degeneration who currently do not have treatment options available, as well as the potential to bring the company’s gene therapies to patients with orphan inherited retinal diseases who also do not have treatment options available.”

Dr. Dugel was previously Managing Partner, Retinal Consultants of Arizona and the Retinal Research Institute; Clinical Professor, USC Eye Institute, Keck School of Medicine, University of Southern California; and founding member, Spectra Eye Institute in Sun City, Arizona. Dr. Dugel is widely published, and has also served as editor of the Retinal Physician column Clinical Trial Download.

“We are excited to add Pravin to our management team,” said Sblendorio. “In addition to being a globally recognized retinal specialist, Pravin brings an extensive network and long-standing relationships with the biotech/pharma ophthalmic industry. With Iveric bio’s portfolio of multiple ongoing retinal disease therapeutic and gene therapy R&D programs, Pravin’s experience will be instrumental in helping us build alliances with potential future collaborators and other stakeholders. We look forward to Pravin’s input and perspective as we move the company forward.”

Three Companies Raise Capital After Positive Studies

Encouraging data reported from trials for IRDs and AMD.

■ Adverum Biotechnologies, Applied Genetic Technologies (AGTC), and Iveric bio have solidified their financial positions after releasing positive clinical trial data in their efforts to combat a range of retinal diseases. The 3 publicly traded companies each sold stock recently as investors took note of their promising prospects.

AGTC raised $32.5 million after reporting positive results in early-stage clinical trials for the inherited retinal diseases X-linked retinitis pigmentosa and achromatopsia. Adverum raised $150 million in a public stock offering after announcing continuing positive results from its OPTIC 1 study of gene-derived anti-VEGF for the treatment of wet AMD. Some patients in the study have gone 50 weeks or more without the need for retreatment after a single intravitreal injection. Iveric bio announced gross proceeds of approximately $40 million from a combination common stock and warrants offering. The company recently announced positive data from a phase 2b clinical trial of its complement C5 inhibitor Zimura (avacincaptad pegol) for the treatment of geographic atrophy secondary to dry AMD. The trial resulted in statistically significant reduced lesion growth at the 12-month mark. Iveric bio recently announced the study design for a second pivotal trial of Zimura for the GA indication.

IN BRIEF

Research and industry news in retina.

BY JERRY HELZNER, CONTRIBUTING EDITOR

Antiviral Drug Should Not Cause Retinal Toxicity

■ Because of intense interest in finding immediate therapeutics for the COVID-19 illness, a number of small trials have been quickly initiated around the globe to determine whether chloroquine (CQ) and hydroxychloroquine (HCQ, sold under the brand name Plaquenil [Novartis], among others) can be of value in minimizing the effects of this rampant disease. These antiviral drugs are primarily used to treat malaria but are also used for systemic lupus erythematosus (SLE) and other rheumatoid diseases. The FDA has now approved the antivirals for emergency use, and Novartis has donated 30 million doses of hydroxychloroquine.

As Michael F. Marmor, MD, of the Byers Eye Institute, Stanford University, pointed out in an article published in Science Direct, CQ and HCQ are familiar to ophthalmologists because of retinal toxicity after long-term usage for SLE and rheumatoid diseases. Dr. Marmor noted, however, that even very high CQ/HCQ doses do not cause retinal toxicity if they are used for a short period of time. Although the doses reported to have been used in COVID-19 cases are extremely high, the drug is used for a very brief period of time. He also reports “that some rheumatologists had been giving 1,200 mg/day for 6 weeks as a loading dose when starting HCQ for SLE, and no visual loss was seen, although detailed ophthalmologic exams were not performed.1,2 Similar outcomes were seen in trials for myeloma3,4 and small-cell lung cancer.5

“Evidence to date indicates that extreme doses do accelerate retinal toxicity, but with a probable time course of many months rather than days,” Dr. Marmor asserts.

Editor’s note: Find the references cited here and an expanded version of this story at https://www.retinalphysician.com/issues/2020/april-2020/antiviral-drug-should-not-cause-retinal-toxicity .

Physicians Ask HHS for Medicare and Medicaid Payments

■ The AAO, ASRS, and ASCRS have joined with numerous other major physician advocacy organizations in a letter to HHS Secretary Alex Azar to request immediate Medicare and Medicaid payments due to decreased activity in their practices because of COVID-19.

“Congress intended to provide relief to physician practices who are suffering financial loss due to COVID-19 by designating funding in the Public Health and Social Services Emergency Fund in the Coronavirus Aid, Relief and Economic Security (CARES) Act,” the letter says. “The statute requires HHS to interpret eligibility for the funding broadly to include all physicians who are experiencing revenue losses and nonreimbursable expenses as a result of the COVID-19 pandemic.”

The letter notes that many physicians who practice in offices and ambulatory surgical centers are not seeing patients for nonessential visits in order to slow the community spread of COVID-19. Specifically, the letter urges HHS to provide 1 month of revenue to each physician, nurse practitioner, and physician assistant enrolled in Medicare or Medicaid to account for financial losses and nonreimbursable expenses.

Companies Extend Anti-VEGF Payment Terms

■ In response to the COVID-19 pandemic, both Regeneron (aflibercept; Eylea) and Genentech (ranibizumab; Lucentis) have temporarily extended physician payment terms for their anti-VEGF purchases from authorized distributors. In the case of Eylea, physicians may be temporarily eligible for payment terms of up to 150 days (previously 100 days), subject to distributor qualification. Ophthalmologists are urged to verify the timing and specific dating terms that apply to their offices with their authorized distributors of record. This has no impact on current Eylea return policies.

Regeneron implemented these new temporary terms April 1. These terms apply retroactively for Eylea (vial or prefilled syringe) purchased on or after March 1, 2020. Genentech said it will temporarily extend physician payment terms for Lucentis purchases from 60 days to 120 days, according to a company news release. Purchases from April 1, 2020, as well as retroactively for purchases made on or after March 1, 2020, will be eligible for the extension.

COVID-19 Not Likely Spread by Tears

■ In an effort to determine whether the COVID-19 virus could be spread by tears, researchers from the Duke-National University of Singapore Hospital collected 64 tear samples from 17 COVID-19 patients between Day 3 to Day 20 from initial symptoms. Neither viral culture nor reverse transcription polymerase chain reaction detected the virus, suggesting a low risk of ocular transmission.

Lead researcher Ivan Seah, MD, also took samples from the back of the nose and throat during the same time period. While the patients’ tears were clear of virus, their noses and throats tested positive. Dr. Seah said he hopes their work helps to guide more research into preventing virus transmission through more significant routes, such as droplets and fecal-oral spread. The research was recently published in the journal Ophthalmology.

Graybug Will Use Only 1-Mg Dose In Wet AMD Trial

■ Graybug Vision announced the early closing of enrollment in its ALTISSIMO trial. ALTISSIMO is a phase 2b, 12-month, multicenter, prospective, masked, randomized trial that began by comparing each of 2 dosing regimens of GB-102 (1 mg or 2 mg), administered every 6 months, to aflibercept, administered every 2 months, in patients with anti-VEGF-responsive wet AMD. However, since launching ALTISSIMO, a limited interim safety analysis supports Graybug’s intention to take the 1 mg dose forward for further exploration in clinical trials, ultimately resulting in the acceleration of the ALTISSIMO final data analysis by approximately 6 months.

“GB-102 has the potential to help patients control their disease by addressing the treatment burden of wet AMD with a single injection every 6 months. Improving the safety of GB-102 by reducing the rate of anterior chamber migration of microparticles is important for both clinicians and patients. This has been a key focus in multiple ongoing trials and the data has now shown that the 1 mg dose of the newly optimized formulation is appropriate for use in the pivotal trials,” said Arshad M. Khanani, MD, MA, managing partner and director of clinical research at Sierra Eye Associates and clinical associate professor of ophthalmology at the University of Nevada in Reno.

Graybug’s lead product candidate, GB-102, a microparticle depot formulation of the anti-VEGF sunitinib malate, seeks to reduce the need for frequent intravitreal injections by expanding treatment duration to 6 months and reducing the burden of current treatments. Emerging evidence from Graybug’s 3 dose-finding clinical trials suggests that 1 mg of GB-102 may offer greater safety and tolerability than the 2-mg dose.

Topcon Offers Free Breath Shields for Slit Lamps

■ Eye doctors are required to be in close contact with patients while performing an exam and thus unable to maintain the CDC recommended distance of 6 feet during the coronavirus pandemic. In order to combat this and prevent the transmission of respiratory illnesses, including COVID-19, Topcon is now offering all of its slit lamp customers a free breath shield that fits onto their instrument and provides a first line of defense for both health care providers and patients. Registration is available at https://info.topconhealthcare.com/request-free-breath-shields/ .

ImprimisRx, ModMed to Provide Free Telemedicine Services

■ Harrow Health and ImprimisRx, a wholly owned subsidiary of Harrow, have entered into an exclusive agreement with Doxy.me , a full-service telemedicine solution. This agreement will provide all ImprimisRx ophthalmology practices with the clinic-level Doxy.me telemedicine solution at no charge. Doxy.me is one of the largest telemedicine software solutions in the world, providing video, audio, and text, through which patients and healthcare providers can seamlessly communicate remotely.

In a similar move, health care information technology company Modernizing Medicine said current and future users of its electronic health records system, EMA, will have access to its real-time audio and video telemedicine platform, modmed Telehealth. The solution will help healthcare professionals treat existing patients when it’s needed most during the spread of COVID-19.

ReNeuron Sees Strong Vision Gains in RP

■ ReNeuron Group plc announced positive 12-month data from the ongoing phase 1/2a clinical trial of its hRPC stem cell therapy candidate in retinitis pigmentosa (RP) and plans to expand the ongoing study. At 12 months, 3 patients gained a mean of 14.3 letters in the treated eye and 7.0 letters in the untreated eye.

The company has submitted a protocol amendment to the FDA to expand the phase 1/2a study to treat up to a further 9 patients in the phase 2a segment of the study with a dose of 2 million hRPC cells, which compares with the dose of one million cells used in the study thus far. The amended clinical trial protocol also allows for a greater range of pretreatment baseline visual acuity in patients and includes changes that enhance the ability to use microperimetry testing to measure and detect changes in retinal sensitivity in patients treated.

The company and its clinical advisers believe that this protocol amendment will enable the efficacy signal observed in the study thus far to be both better delineated and magnified when demonstrated in a larger and more closely defined group of RP patients. RP

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