Genentech Acquires Developer of Sustained-Release Implants

ForSight Vision4 supplies reservoir for Lucentis delivery.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ Genentech (Roche Holding) clearly signaled that it believes in the future of sustained-release delivery of biologic drugs that treat retinal disease when it acquired ForSight Vision4 late last year. ForSight has been collaborating with Roche’s Genentech division since 2010 when it licensed the exclusive rights to its refillable rigid port delivery system (RPDS) to Genentech as an initial step toward offering Lucentis (ranibizumab) in a sustained-release format.

Currently, the ophthalmic drugs approved by the FDA for sustained-release delivery have been almost exclusively limited to steroids. These approved drugs include Ozurdex (Allergan) for uveitis and DME, Iluvien (Alimera Sciences) for DME, and Retisert (Bausch + Lomb) for uveitis.

The RPDS is a durable intravitreal implant that is placed through a scleral incision in a one-time surgical procedure. The timing for refills is currently being studied but it is estimated by the company at 4 to 6 months. Currently in a phase 2 clinical trial, it could potentially replace intravitreal injections of Lucentis now normally given every 4 to 6 weeks.

TECHNOLOGY FROM AN OPHTHALMIC INCUBATOR

Terms of the ForSight Vision4 acquisition included an upfront payment and additional payments for meeting certain clinical and commercial milestones. ForSight Vision4, which is focused on the development of sustained-release delivery for a range of therapeutic agents, is one of a number of new companies that have come out of the ForSight Labs ophthalmic incubator.

In recent years, Genentech has been moving sustained-release technology through early-stage clinical trials. Currently, the company is conducting the 220-patient phase 2 LADDER study that, if successful, would bring doctors and patients one step closer to a less burdensome treatment regimen requiring fewer office visits and injections.

Genentech researchers have long believed that ranibizumab could be successful in a sustained-release format, because the drug has the stability to remain effective for months when placed in an implant.¹

In the small phase 1 study, the RPDS implant was well tolerated and showed an improvement in visual acuity comparable to monthly Lucentis injections, establishing proof of concept for the system. Genentech’s RPDS implant also has received fast-track designation from the FDA.

“With the investigation of the RPDS implant, we hope to provide patients with the maximum benefits of treatment with Lucentis while reducing the number of office visits and injections they require,” said Jill Hopkins, MD, medical director, Genentech Ophthalmology, in an announcement about the product.

REFERENCE

1. Helzner J. Anthony P. (Tony) Adamis, MD: a giant in the fight against retinal disease. Retinal Physician. 2015;12(1):25-26. http://www.retinalphysician.com/issues/2015/jan-feb/innovation-in-retina .

Should Every Patient Be Genetically Profiled?

A useful tool toward more personalized evaluation.

■ Studies have found that while macular degeneration patients clinically present similarly, 40% respond differently to the same drugs and dosages, says Pravin Dugel, MD, of Retinal Consultants of Arizona. In the future, personalized medicine may be the answer to containing costs while improving the quality of care.

“What we’re realizing is that we need to look at the genotype of the patient and personalize the diagnostics and therapeutics for that particular person,” he says.

In recent years, increasing attention has been paid to the role of genetics in retinal disease. A genetic profile can be predictive of an individual’s risk for retinal disease. It also has potential for being a useful diagnostic tool, pointing practitioners to specific therapies that may be effective for an individual patient. For the longer term, there is the promise of gene therapy, in which a defective gene is replaced by a healthy one, facilitating a cure.

Genetics is already influencing efforts to combat retinal disease. Commercial companies such as Arctic DX are teaming with ophthalmologists to offer relatively simple genetic tests (a cheek swab taken in the doctor’s office) designed to evaluate the risk profile of individuals who have either been recently diagnosed with AMD or who have a family history of AMD.

Genentech genetically profiled every patient in its phase 2 MAHALO clinical trial using the drug lampalizumab for dry AMD and found that specific genetic subsets of patients got more therapeutic benefit from the drug than other subsets. Genentech believes that this was the first ophthalmic clinical trial in which all patients were genetically profiled.

In 2014, Regeneron embarked on a collaboration with Geisinger Health System to genetically profile at least 100,000 individuals to develop a database for future drug development that encompasses genetic factors. During the initial 5-year collaboration term, Geisinger plans to collect samples from consented patient volunteers, while Regeneron, through its subsidiary, Regeneron Genetics Center LLC, will perform sequencing and genotyping to generate deidentified genomic data. The size and scope of the study are meant to facilitate precision in identifying and validating the associations between genes and human disease.

“Genetics has been at the core of our research efforts at Regeneron since its early days,” said George D. Yancopoulos, MD, PhD, chief scientific officer and president, Regeneron Laboratories, in a press release. “In fact, our first FDA-approved therapy treats a rare genetic disorder, and the target of one of our product candidates in late-stage development that acts to lower LDL cholesterol was identified using human genetics.”

Some in the retina community are advocating that patients considering taking eye health supplements to reduce the risk of macular degeneration should first be genetically profiled to determine if the supplements would be of any benefit. This position has sparked fierce debate in the retina community, with studies on the merits of supplements for specific patient cohorts being both cited and challenged.

While the initiatives and efforts outlined above are still at an early stage, Dr. Dugel’s view that retinal disease is highly individualized and must be treated as such is borne out by the widely varying effectiveness of specific therapies with selected patients. Thus, genetic profiling offers one potential avenue to achieving a more personalized and successful approach to combating retinal disease.

Aura Biosciences’ New Approach to Ocular Melanoma

Therapy targets only malignant cells.

Aura Biosciences is preparing to soon begin its first human clinical trial for its AU-O11 combination drug/laser therapy that is designed to selectively bind virus-like therapeutic particles (VLPs) to cancer cells and then eliminate only those malignant cells through laser activation of the particles. The FDA recently cleared Aura to begin a phase 1b, dose-ascending clinical study treating small to medium ocular melanoma at 5 sites in the United States.

In vivo results presented at the ARVO annual meeting demonstrated how synthetic VLPs modeled on the human papillomavirus (HPV) are able to bind uniquely to cancer cells while leaving healthy surrounding tissue unharmed. The authors determined that tumor cells differ from healthy cells in the over-expression and modifications of heparan sulfate proteoglycans on their membrane as well as on the extracellular matrix, which provides a unique binding site for HPV variations and for engineered VLPs.

Currently, ocular (or uveal) melanoma is usually treated with surgery and radiation, though the type of radiation used varies with a number of factors, including the size and location of the tumor. Best outcomes are achieved when the disease is caught at an early stage, though enucleation of the eye is often necessary. Once the disease metastasizes to the liver, it is nearly always fatal. Many studies have shown that the incidence of ocular melanoma is greatest among white males over the age of 60.

Aura said its selective targeting approach should be effective with a number of cancers but has chosen ocular melanoma for its initial human test. The company received $21 million in venture capital funding in 2015. In addition, AU-011 was granted orphan drug status by the FDA last year.

“There are currently no approved drug therapies for the treatment of uveal melanoma, which is a rare but life-threatening disease. We are thrilled to receive this Orphan Drug Designation that, together with the positive preclinical data, is enabling us to move this drug one step closer to the clinic,” says Elisabet de los Pinos, founder and CEO of Aura Biosciences, in a statement.

Fellows’ Forum Introduces “Real World” Retina

Dr. Gary Abrams gives guest lecture.

■ The 17th annual Retina Fellows’ Forum took place on January 27 and 28 in Chicago, Illinois. Seventy North American vitreoretinal fellows from 60 programs participated in an educational and social program that has become an anticipated fixture of the final year of vitreoretinal training.

As in past years, the fellows spent considerable time in the lecture hall with a panel of faculty led by course director Dr. David Chow and co-directors Drs. Carl Awh and Tarek Hassan. Drs. Dean Eliott, Mike Jumper, Peter Kaiser, Tamer Mahmoud, Jon Prenner, and Amy Schefler completed the faculty.

The opening session focused on controversies and current research in AMD. The faculty debated anti-VEGF treatment strategies and drug selection, with the fellows voting for “winners” using an audience response system. Lectures and discussion about the role of genetic testing in the management of AMD and of current and future clinical trials rounded out the AMD session. A surgical video rounds session featured a series of challenging cases and panel discussion that emphasized the many “correct” ways to attack a surgical problem.

Saturday offered a full day of panel-driven discussions and one-on-one faculty debates on retinal detachment, retinal vein occlusion, diabetic retinopathy, trauma, macular surgery, dislocated IOLs, and surgical instrumentation. A highlight of the meeting was the distinguished guest lecture, this year delivered by Dr. Gary Abrams on “Pivotal Moments in Vitreoretinal Surgery,” an inspiring reflection on his life and career. The afternoon concluded with a “Real World” panel discussion devoted to career decisions, practice-building, and balancing work and personal demands.

The prestigious and competitive Retina Fellows’ Forum research award went to Dr. Bozho Todorich of Associated Retina Consultants for his paper, “Structural Analysis and Long-Term Surgical Outcomes of the Sutureless Intrascleral Fixation of Secondary Intraocular Lenses in Human Eyes.” Dr. Todorich will present his paper at the 2017 annual American Society of Retina Specialists meeting as a specially recognized lecture.

VisionCare Seeks to Expand IMT Indications

New trial for post-cataract patients.

■ VisionCare, Inc., a developer of advanced visual prosthetic devices for the treatment of end-stage AMD, said the FDA has approved the company’s investigational device exemption for a new US clinical study of the Implantable Miniature Telescope (IMT). The study will for the first time evaluate the safety and effectiveness of the telescope implant in patients who were previously implanted with an IOL. In the study, the IOL will be exchanged for the IMT in a team procedure that always includes a retina specialist.

Called the Telescope Exchange Study (TES), the trial will encompass 75 patients age 65 and older with best-corrected distance visual acuity of 20/160 to 20/800. Principal investigators will be Stephen S. Lane, MD, of Associated Eye Care, Stillwater, Minnesota, and Derek Kunimoto, MD, JD, of Retinal Consultants of Arizona in Phoenix. Patients will be followed for at least 3 years post implantation.

Under current indications, the telescope implant is proven to improve visual acuity and quality of life for patients with end-stage macular degeneration whose sight is permanently obstructed by a blind spot in their central vision (in both eyes), making it difficult or impossible to see faces, read, and perform everyday activities such as watching TV, preparing meals, and self-care. It is the only FDA-approved surgical device for end-stage macular degeneration and is Medicare eligible.

According to current labeling, the telescope implant is contraindicated in patients with previous intraocular or corneal surgery of any kind in the operative eye, including any type of surgery for either refractive or therapeutic purposes.