Macugen Approved for Wet AMD
Drug Is OK'd for All Lesion Subtypes and Sizes.
The FDA has approved pegaptanib sodium injection (Macugen) for the treatment of wet AMD. The Eyetech/Pfizer drug is the first therapy indicated for the treatment of all types of neovascular AMD, regardless of lesion subtype or size.
The only other FDA-approved treatment for wet AMD is verteporfin for injection (Visudyne). This therapy is reimbursed by Medicare for predominantly classic, and some types of occult and minimally classic AMD.
The FDA approval for pegaptanib sodium was based on findings from two pivotal phase 2/3 randomized, multicenter, double-masked clinical trials involving approximately 1200 patients with all subtypes of neovascular AMD. The primary efficacy endpoint was the proportion of the patient cohort protected from 3-line loss of visual acuity on the eye chart by week 54.
Results showed that among patients receiving 0.3 mg of pegaptanib sodium, 70% lost less than 3 lines of vision on the eye chart, compared with 55% of patients receiving control treatment. The results demonstrated a 27% relative treatment effect for pegaptanib sodium-treated patients compared with controls with respect to 3-line loss. Pegaptanib sodium also helped limit progression to legal blindness, by 50% compared with controls, in the study eye. Two-year clinical data from the studies demonstrated a continued treatment benefit.
Approval follows a priority review under the FDA's rolling submission-Pilot 1 program based on data from the companies' phase 2/3 pivotal clinical trials. It also follows a unanimous recommendation for approval from the FDA Dermatologic and Ophthalmic Drugs Advisory Committee.
Pegaptanib sodium is the first in a new class of ophthalmic drugs to specifically target vascular endothelial growth factor (VEGF), a protein that acts as a signal in triggering the abnormal blood vessel growth and leakage that is the hallmark of neovascular AMD.
"Macugen is the first antiangiogenic treatment approved in ophthalmology and represents the beginning of a new era. The antiangiogenic approach specifically addresses, for the first time, an underlying cause of blindness in age-related macular degeneration. Antiangiogenesis has now evolved from theory to therapy," said Judah Folkman, MD, Julia Andrus Dyckman professor of Pediatric Surgery at Children's Hospital in Boston and Harvard Medical School.
Fifteen million people in the United States are living with some form of AMD, with more than 1.6 million experiencing the active blood vessel growth and blood vessel leakage associated with wet AMD. More than 200 000 new cases of wet AMD are diagnosed each year and this number is expected to increase significantly as the baby boom generation ages and overall life expectancy increases. Currently, more than 500 000 people worldwide lose their sight annually from the disease.
"The FDA's approval of Macugen for all neovascular age-related macular degeneration represents an important paradigm shift in the treatment of this devastating disease. Macugen is a novel treatment based on elegant science that for the first time targets the underlying cause of the disease, which has led to our broad AMD label, including all subtypes and sizes," said David R. Guyer, MD, CEO and co-founder of Eyetech Pharmaceuticals.
Pegaptanib sodium is a pegylated anti-VEGF aptamer, a single strand of nucleic acid that binds with specificity to a particular target. It specifically binds to VEGF 165, a protein that plays a critical role in angiogenesis and increased permeability, two of the primary pathological processes responsible for the vision loss associated with neovascular AMD.
Pegaptanib sodium is administered in a 0.3 mg dose once every 6 weeks by intravitreal injection. Eyetech and Pfizer plan to make the treatment available in the first quarter of 2005, with an announced initial list price of $995 per injection.
Study: Stem Cells Can Preserve Vision
Researchers See Potential Use in Retinal Diseases.
In a groundbreaking study, researchers from Harvard's Schepens Eye Research Institute have shown that transplanted stem cells can preserve -- and even improve -- vision in eyes damaged by retinal disease.
The researchers said results of a mouse study demonstrated that transplanted stem cells can develop into new retinal cells, prevent the death of "at risk" retinal cells, and improve the vision of treated mice. The results were published in the November issue of Investigative Ophthalmology and Visual Science.
"These findings hold great promise for potential treatments for people suffering from macular degeneration, diabetic retinopathy and other retinal diseases," says Michael Young, PhD, an assistant scientist at Schepens and the lead author of the study.
Beginning with the premise that stem cells have the capacity to change into other kinds of cells, Young and his team transplanted retinal cells from young "green" mice into the eyes of normal-colored mice with retinal disease. Green mice are genetically raised so that all of their tissue is fluorescent green, which makes it possible to detect where the transplanted cells are and how they are growing and changing.
After several weeks, the team evaluated the eyes of the treated mice and found that the green cells had migrated to where they were needed in the damaged retina and had changed into what looked like normal retinal cells. The scientists also found that many of the retinal cells that were on the verge of dying before the transplant appeared to regain or retain their function. The researchers speculated that the transplanted cells were secreting a factor or substance that saved these fragile cells.
To test whether the mice with transplanted stem cells could see better, the team then placed them and a group of nontreated control mice in separate dark cages and flashed a series of increasingly lower level lights at both groups over a period of time. Being photophobic, mice stop their normal activity when they detect light. The researchers took advantage of this natural response and found that the mice with the transplanted cells continued to respond to the light as it reached its lowest levels. The control mice did not.
The team is now investigating the use of stem cells in pigs, whose eyes are larger and more like human eyes.
Talia appointment. Daniel D. Biondi has been named president of Talia Technology's North American operations. Biondi was formerly senior vice president of Olympus America, a subsidiary of Olympus Optical Ltd. Of Japan.
Talia Technology develops and markets retinal imaging instruments for the diagnosis and monitoring of glaucoma and various retinal pathologies.
Retaane NDA. Alcon, Inc. has submitted the third and final reviewable unit of its New Drug Application (NDA) for anecortave acetate for depot suspension (Retaane 15 mg) to the FDA. The application is subject to formal acceptance by the FDA, which could take up to 45 days from the date of submission. Alcon also has submitted its European Marketing Authorization Application for anecortave acetate. Alcon is seeking approval of the drug as a treatment for patients with subfoveal choroidal neovascularization due to wet age-related macular degeneration.
In the United States, anecortave acetate is being reviewed under the FDA's new Pilot 1 Continuous Marketing Application program for fast track designated products, which allows designated NDAs to be submitted in specified reviewable units as each is completed, with each one assigned its own 6-month review target.
The FDA has completed its initial review of the anecortave acetate Chemistry, Manufacturing and Controls unit, which was filed in 2003, and the Pre-Clinical unit, which was filed in March 2004. Alcon has responded to all questions posed by the FDA to date. The FDA also has completed its pre-approval inspection of Alcon's manufacturing facility, with no negative findings.
Single-use spreading agent. ISTA Pharmaceuticals, Inc. said the FDA has approved a single-use vial (200 USP Units/mL) of hyaluronidase injection ovine sterile solution (Vitrase) for use as a spreading agent to facilitate the dispersion and absorption of other drugs in ophthalmic procedures. The product is a proprietary formulation of highly purified, preservative-free ovine hyaluronidase, which has been studied extensively in several ophthalmic conditions.
Vicente Anido, Jr., PhD, ISTA's CEO, said "We are pleased with the current approval and anticipate that we will launch the new vial size, as well as the previously approved 6200 USP Units multipurpose vial, early in the first quarter of 2005. We believe the smaller-sized vial will greatly enhance the convenience of using Vitrase as a spreading agent by ophthalmologists. Further, the availability of Vitrase provides ophthalmologists with a preservative-free alternative to other available hyaluronidases, including non-FDA approved hyaluronidases sold by compounding pharmacies."
In May, the FDA approved hyaluronidase ovine in a 6200 USP Units multipurpose vial.
Retisert NDA. The FDA has accepted for review the NDA for Bausch & Lomb's patented Retisert intravitreal implant for noninfectious uveitis affecting the posterior segment of the eye. The implant is designed to deliver to the back of the eye a sustained release of the well-known steroid fluocinolone acetonide for up to 3 years.
The application has FDA Fast Track status, designed to allow for quicker, priority review of novel therapies for serious diseases for which there is an unmet medical need.
Alcon grant. Alcon has committed $1.125 million over 5 years to back the Seniors EyeCare Program of EyeCare America, the public service arm of the Foundation of the American Academy of Ophthalmology. The Seniors EyeCare Program provides dilated eye examinations and up to a year of treatment at no out-of-pocket cost to eligible seniors.
The program is designed to help individuals age 65 or older who haven't seen an ophthalmologist in 3 years, and who don't belong to an HMO or the VA. Those eligible for the program are referred to one of EyeCare America's 7500 participating volunteer ophthalmologists.
GenVec receives grant. GenVec, Inc. said it has received a 2-year, $750 000 Small Business and Innovative Research (SBIR) grant from the National Eye Institute (NEI) to support research on the biological properties of Pigment Epithelium-Derived Factor (PEDF). PEDF, a protein naturally produced in the eye, regulates blood vessel growth and acts to protect the eye cells that sense vision.
Acuity Moves Ahead with Wet AMD Drug
Cand5 Shuts Down VEGF Production.
K Founded just 2 years ago, Acuity Pharmaceuticals appears to be a David against several Goliaths in its efforts to bring a new treatment for wet AMD through clinical trials and into the marketplace. However, Acuity believes it has an advantage over its larger rivals because its drug uses the newly discovered gene-silencing mechanism of RNA interference (RNAi) to prevent the production of the protein that causes choroidal neovascularization (CNV), while other treatments bind the protein after it's been produced.
"Our drug, Cand5, basically shuts down the main stimulus for the disease," says Samuel Reich, cofounder and head of corporate development for Acuity. "Cand5 shuts down the production of vascular endothelial growth factor (VEGF), a central player in the development of CNV, and actually suppresses VEGF before it's made. Other anti-VEGF drugs use a protein antagonist to bind VEGF."
Reich says the ability to attack the cellular machinery that produces VEGF gives Cand5 a major therapeutic advantage. "Once the VEGF proteins are produced, it takes one molecule of drug to inactivate one molecule of VEGF," he notes. "With Cand5, one molecule of the drug can shut down the production of thousands of potential VEGF proteins." Thus far, Acuity has demonstrated good evidence of safety and efficacy in disease models of macular degeneration.
In October, Acuity's Cand5 became the first RNAi therapeutic to enter human clinical studies when its phase 1 trial commenced. "The drug will initially be administered through an intravitreal injection," says Reich. "It's a very potent drug, but because it's synthesized from a naturally occurring substance, ribonucleic acid, we don't expect to see much in the way of side effects. There were no adverse effects in the animal studies." Reich says the small-molecule drug could eventually be administered as an eye drop.
"Most of the other anti-VEGF drugs currently being developed started out as treatments for cancer," says Reich. "Acuity set out to design drugs specifically to treat AMD and diabetic macular edema. We believe Cand5 can be used alone or, eventually, in combination with other treatments."
Acuity, based in Philadelphia, completed a series B financing this fall and would consider a partnership with a large pharmaceutical company once it has accumulated additional clinical data. The company is headed by Dale Pfost, PhD, an experienced builder of biotech companies, and claims to have a strong intellectual property position in the category of drugs called "small, interfering RNA" or siRNA.
"Now that we are actually dosing patients, it's difficult to convey the extent of our excitement for this very promising new approach to treating AMD," concludes Reich.