SUBSPECIALTY NEWS
Ocata Injects RPE Cells to Combat Retinal Diseases
Company currently has three studies under way.
BY JERRY HELZNER, CONTRIBUTING EDITOR
■ Ocata Therapeutics (Marlborough, MA) believes that it has a better way than drugs to combat serious retinal diseases. It’s called “regenerative ophthalmology.”
Ocata, formerly known as Advanced Cell Technology, is now injecting human-derived embryonic retinal pigment epithelium stem cells in three small clinical trials. The trials are for dry AMD, Stargardt disease, and myopic macular degeneration.
The company reports that of the 38 people who have received its RPE cell therapy to date in the phase 1/2 trials, most have achieved improved vision, including one patient who went from 20/400 to 20/40 in a matter of weeks. Ocata said no safety issues have yet been reported.
Just recently, Ocata received written formal regulatory guidance from the European Medicines Agency as to how to best advance its Stargardt’s RPE program into a pivotal clinical trial that could result in marketing authorization. As a result of this guidance, Ocata now plans a 100-patient trial with an untreated control group.
Ocata’s also has preclinical programs that involve cell therapies for the treatment of other ocular disorders and for diseases outside the field of ophthalmology, including autoimmune, inflammatory, and wound healing-related disorders.
The progress of Ocata and other stem cell initiatives will be discussed by a panel of experts at a symposium sponsored by the Ocular Research Symposia Foundation and held at the Hotel Casa del Mar in Santa Monica, CA, on June 12-13. More information is available at www.theorsf.org.
IN BRIEF
■ Bayer to study eyedrop for wet AMD. Bayer HealthCare (Whippany, NJ) plans a 350-patient phase 2 study to determine if its regorafenib anti-angiogenic in an eyedrop format can be effective in combating wet AMD. Regorafenib has already received FDA approvals as an oral therapeutic for two types of cancer.
The wet AMD study, which is currently recruiting treatment-naïve patients, will have primary endpoints of vision improvement at both four and 12 weeks. The study, known as DREAM, will also evaluate how different doses of the eyedrop affect patients’ vision, safety, and tolerability.
One arm of the multi-arm study will use Lucentis (ranibizumab, Genentech) as a comparator.
■ Squalamine eyedrop fails wet AMD endpoint. Final topline data from the nine-month phase 2 IMPACT study conducted by Ohr Pharmaceutical (New York, NY) have confirmed previously released interim results of a failed primary endpoint for its topical treatment for wet AMD.
The complete data again demonstrates no reduction in the number of anti-VEGF injections needed over nine months by patients being treated with a combination of the (self-administered) Ohr squalamine aminosterol eyedrop and anti-VEGF for wet AMD.
On the positive side, 42% of the patients with classic CNV who received the combination gained greater than three lines of vision at nine months, while 28% of the patients who received only anti-VEGF monotherapy (ranibizumab) achieved similar vision gains. Less of a vision benefit was seen in patients with the occult form of wet AMD.
In a statement released with the results, Ohr indicated that the company plans to conduct a phase 3 clinical trial for the squalamine eyedrop in wet AMD. That trial is expected to begin late this year.
In other Ohr news, the company said new data from its IMPACT study interim analysis show an early regression of subretinal hyper-reflective material (SHRM), an anatomic biomarker for wet AMD, which is consistent with the early gains in visual acuity previously reported from this study.
■ Warning on calcium supplements and AMD. People age 68 and over who take more than 800 mg of calcium supplements on a daily basis may be at nearly twice the risk of developing macular degeneration, according to a study of 3,191 individuals recently reported in the online edition of JAMA Ophthalmology.
Researchers cautioned that the study found an “association” between calcium supplements and AMD but did not identify the supplements as a cause of the disease.
Neurotech Implant to Move into Phase 2 Trial
One injection treats wet AMD for two years.
■ Neurotech Pharmaceuticals (Cumberland, RI) said the FDA has given the company approval to conduct a phase 2 clinical study of NT-503 encapsulated cell therapy (ECT) for the treatment of recurrent subfoveal choroidal neovascularization secondary to AMD. The implant holds specially engineered retinal pigment epithelial cells that continuously produce therapeutic VEGF-receptor proteins over a period of two years.
The phase 2, randomized, active-controlled, masked study will enroll 150 patients. The safety and efficacy of one NT-503 ECT implant will be compared to aflibercept (Eylea, Regeneron) intravitreal injections every eight weeks in patients who have been treated with at least three anti-VEGF injections and still have active disease. Patients will be followed for two years with a 12-month interim assessment.
“The NT-503 ECT implant, essentially a reversible gene therapy, represents the future of intraocular drug delivery,” said study investigator David Boyer, MD, senior partner at Retina-Vitreous Associates Medical Group in Los Angeles. “To have a therapy that could effectively and continuously treat our AMD patients long-term without the burden of frequent injections is very exciting. It is also advantageous to have the option of removing the implant, if desired.”
“This is a significant milestone for our NT-503 ECT program,” said Quinton Oswald, CEO of Neurotech. “Real-world injection frequencies often do not correlate with optimal treatment recommendations due to the enormous burden of monthly or bimonthly injections and disease monitoring. We are one step closer to being able to give patients and physicians an efficacious, long-term therapy with a single outpatient surgical procedure.”
IN BRIEF
■ First Argus II implanted in Hawaii. Gregg T. Kokame, MD, and a team from the Eye Surgery Center of Hawaii implanted the first Argus II retinal prosthesis (Second Sight Medical, Sylmar, CA) in Hawaii in a patient with retinitis pigmentosa. Dr. Kokame is the founder of Retinal Consultants of Hawaii and president of Eye Surgery Center of Hawaii.
The procedure is the first to be performed in the Asia-Pacific region, with more patients scheduled to receive the Argus II at the center.
In related news, Second Sight said the first successful implant of the company’s next-generation Orion I system has been achieved in an animal study. The Orion I bypasses the retina and optic nerve to interface with the visual cortex of the brain, making the device applicable to many blinding diseases and conditions.
“Following the success of Argus II in patients with retinitis pigmentosa, we are looking forward to extending the hope of restoring some useful vision to nearly all blind individuals with the Orion I,” said Robert Greenberg, MD, PhD, president and CEO of Second Sight.
■ Iluvien approved for chronic DME in Poland. Poland became the 17th European country to approve the Iluvien (Alimera Sciences, Alpharetta, GA) sustained-release implant for the treatment of chronic DME. Iluvien also recently became commercially available for use in the United States.
■ USC and Retinal Consultants of Arizona form joint program. The USC Eye Institute and Retinal Consultants of Arizona (RCA) have announced a new collaboration to enhance eye care — with a specific focus on a joint educational and research programs.
The USC-RCA vitreoretinal fellowship program will provide fellows with top tier training from ophthalmologists who have years of experience in retina and vitreous surgery and have made significant technical and clinical advancements in the diagnosis and management of vitreoretinal diseases.
Additionally, the collaboration creates an international ophthalmology program for teaching, research, and clinical care. Ophthalmologists from around the world will be able to receive education from leading doctors at both the USC Eye Institute and RCA. The collaboration allows those involved in the program to have access to a wider variety of specialized ophthalmologists, each with their own unique focus and background in the field.
AGTC to Initiate Gene Therapy Trial for XLRS
Studies also planned for other orphan eye diseases.
■ Applied Genetic Technologies Corporation (Alachua, FL), a clinical stage biotechnology company developing adeno-associated virus (AAV)–based gene therapies for the treatment of rare eye diseases, has filed an Investigational New Drug (IND) application with the FDA to conduct a phase 1/2 clinical trial of the company’s gene therapy product candidate for the treatment of X-linked retinoschisis (XLRS).
The company has two more clinical trials planned for achromatopsia and X-linked retinitis pigmentosa. All three have been classified by the FDA as “orphan” diseases, which provides additional exclusivity to the developers of approved treatments for orphan diseases.
Utilizing technology licensed from the University of Florida, AGTC’s XLRS product candidate uses an AAV capsid with surface residues that have been specifically engineered for better penetration to the back of the eye.
The company plans to initiate its clinical study during the second quarter of 2015 and expects to have initial data during the second half of this year.
XLRS is an inherited retinal disease caused by mutations in the RS1 gene, which encodes the retinoschisin protein. XLRS is characterized by abnormal splitting of the layers of the retina, resulting in poor visual acuity in young boys, which can worsen as patients age. There are currently no approved treatments for XLRS.
In related news, AGTC has added Bruce A. Peacock to its board of directors. Mr. Peacock, who has four decades of experience in the drug development industry, was most recently chief business and finance officer for Ophthotech, which is developing medical therapies to treat retinal diseases.
IN BRIEF
■ Topcon launches upgraded Pascal Synthesis. Topcon Medical Systems (Oakland, NJ) has introduced a new version of its original pattern-scanning laser, the Pascal Synthesis. This new scanning laser comes with an extended five-year warranty.
The Pascal Synthesis is Topcon’s premier dual-port pattern scanning retinal laser, available in both 532-nm and 577-nm wavelengths. With pricing comparable to a premium single-spot laser system, Topcon says the Pascal Synthesis allows fast and effective treatment of retinal disorders using clinically proven pattern-generating technology. The Pascal Synthesis employs three precision galvanometers to enhance reliability and achieve laser output control consistency.
■ Sirolimus accepted for European Union regulatory review. Santen Pharmaceutical Co., Ltd. (Emeryville, CA) has announced that the European Medicines Agency has accepted the company’s Marketing Authorization Application filing for the use of intravitreal sirolimus, an investigational mTOR inhibitor, for the treatment of noninfectious uveitis of the posterior segment.
The Marketing Authorization Application filing marks the beginning of a regulatory review process for intravitreal sirolimus, which Santen says has the potential to address an unmet need in the European Union, where noninfectious uveitis of the posterior segment is a leading cause of vision loss.
■ Carl Zeiss to partner with Oraya. Carl Zeiss Meditec (Dublin, CA) and Oraya Therapeutics (Newark, CA) have entered into a collaboration agreement under which Carl Zeiss Meditec will provide funding to help grow the potential for Oraya’s radiation therapy for wet age-related macular degeneration over a period of up to two years. In turn, Carl Zeiss Meditec will receive rights in Oraya reaching up to a majority stake after two years.
Oraya has developed and commercialized a low-energy X-ray radiation therapy that is currently available commercially in Germany, the United Kingdom, and Switzerland. The collaboration is intended to accelerate and expand these initial European market developments. While the specific terms of the agreement were not disclosed, the companies noted that Carl Zeiss Meditec will be making a meaningful strategic investment in Oraya, and that further opportunities to leverage the companies’ respective technical and market expertise and resources will be reviewed.
Avalanche to Attempt to Combat Color Blindness
Company signs agreement with University of Washington.
■ Avalanche Biotechnologies (Menlo Park, CA) has entered into an exclusive license agreement with the University of Washington in Seattle to develop gene therapies based on Avalanche’s proprietary Ocular BioFactory platform for the treatment of color vision deficiency (CVD), commonly known as red-green color blindness.
Avalanche also announced that, outside of the scope of the license agreement, Drs. Jay Neitz, PhD, and Maureen Neitz, PhD, both of whom are faculty in the Washington’s ophthalmology department and CVD experts, have joined its Scientific Advisory Board. They will be technical advisors to the company on the science of vision.
“This agreement with the University of Washington and world-renowned vision scientists Drs. Jay and Maureen Neitz will help us further advance our goal of developing therapeutic products for the millions of people who suffer from CVD,” said Thomas W. Chalberg, Jr., PhD, the founder and chief executive officer of Avalanche “Our proprietary technology enables us to target the retina through intravitreal adeno-associated virus delivery, presenting, for the first time, the opportunity to pursue previously untreatable ophthalmic conditions such as CVD.”
Avalanche will build on gene therapy research conducted by the Neitz research team at Washington. They used gene therapy to confer color vision in two adult male squirrel monkeys that had been color blind since birth. This ground-breaking work demonstrating proof-of-concept for treating CVD was published in the October 2009 issue of the journal Nature.
“Avalanche is performing pioneering research that has the potential to cure CVD,” said Dr. Jay Neitz, professor of ophthalmology. “CVD is just one of the many cone diseases that could be treated with Avalanche’s technology.” RP
IN BRIEF
■ Alkeus has new approach to Stargardt disease. Alkeus Pharmaceuticals (Boston, MA) is planning a 50-patient, 24-month phase 2 trial to study its ALK-001 molecule as an oral treatment for Stargardt disease. Stargardt is the result of a genetic defect that causes poor recycling of Vitamin A, leading to toxic aggregates of the vitamin (called Vitamin A dimers) that cause vision loss. Approximately 30,000 people in the United States have Stargardt disease, with many losing vision at an early age.
The Alkeus therapy, which is essentially a chemically modified form of Vitamin A, is intended to prevent the formation of Vitamin A dimers and promote the formation of healthy Vitamin A. It was proven safe in a phase 1 study of 40 healthy volunteers.
■ AGTC and 4D Molecular Therapeutics form partnership. Applied Genetic Technologies Corporation (Alachua, FL) and 4D Molecular Therapeutics (San Francisco, CA), both leaders in the area of gene replacement therapy for serious retina diseases, have agreed to a collaboration and license agreement. The two companies will share their knowledge in discovering and developing optimized adeno-associated virus (AAV) gene vectors to treat specific ophthalmic diseases with urgent medical need.
As part of the agreement, 4DMT will deploy its proprietary AAV vector discovery platform, Directed Vector Evolution, to identify and optimize novel vectors. Financial details were not disclosed.
Sue Washer, President and CEO of AGTC, noted, “We are excited to partner with 4DMT to accelerate development of novel AAV-based gene therapies to treat rare eye diseases. We expect that our combined expertise and our complementary proprietary technology and discovery platforms, will enable us to advance new treatments to market for patients with serious inherited ocular conditions who have few currently available therapeutic options.
“We are thrilled that AGTC, a global leader in ocular gene therapy, has elected to license our optimized next-generation vectors to target specific cell populations within the human retina,” said David Kirn, MD, cofounder and CEO of 4DMT.
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