Full Press Release Details
RETAANE 15mg Depot Clinical Update
Presented at Association for Research and Vision
in Ophthalmology (ARVO) Annual Meeting
FORT WORTH, Texas May 20, 2004 Alcon, Inc. (NYSE:ACL) reviewed data
on the RETAANE 15 mg (anecortave acetate for depot suspension) phase II/III study
and updated information on two new phase III studies of anecortave acetate at the Association for Vision
and Research in Ophthalmology (ARVO) annual meeting in Fort Lauderdale, Fla. In addition, a physician-initiated
study of RETAANE with triamcinolone was reviewed at the meeting. RETAANE
is being developed by Alcon, Inc. as a treatment for successfully preserving the vision of patients
with all forms of wet age-related macular degeneration (AMD). Alcon expects to file a New Drug Application
with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2004. This filing will incorporate
data from a current, multi-center, phase III clinical trial comparing RETAANE with
photodynamic therapy (PDT) in 530 patients with wet AMD. If approved, the company will begin marketing
the product in the first half of 2005.
Phase II/III Clinical Update
Presentations at ARVO showed that RETAANE
was significantly better than placebo for preserving vision, preventing severe vision loss and inhibiting
the growth of all lesion types in patients with wet AMD. At two years, 73 percent of patients treated
with RETAANE showed stable or improved vision, while only 47 percent of placebo-treated
patients showed a similar vision outcome (p = 0.035). In addition, 94 percent of patients experienced
no severe vision loss after two years treatment with RETAANE . At twelve months,
79 percent of patients treated with RETAANE had stable or improved vision, while
only 53 percent of placebo-treated patients showed a similar vision outcome.
New Phase III Studies
Investigator Stephen Russell, M.D., of the
University of Iowa Medical School, Carver School of Medicine, presented an update on Alcon s initiation
of two new phase III studies being conducted in groups of patients with advanced dry AMD who are at
risk of progressing to wet AMD. The studies will evaluate the safety and efficacy of treatment every
six months with anecortave acetate for depot suspension versus a sham procedure. The sham procedure
imitates the procedure used to give patients the investigational drug and is a regulatory requirement
for keeping the study masked as to which patients receive the drug. Anecortave acetate is the first
and only drug of its pharmacological class being investigated to treat this population of at-risk AMD
patients. The FDA has granted Alcon Fast Track designation for the study of anecortave acetate for
this indication because it represents a significant unmet medical need for a serious condition.
Dr. Russell presented the study methods
for the new phase III trials. The protocol states that eligible patients must have, or previously have
had, wet AMD in one eye, while the other eye has no evidence of exudative AMD or geographic atrophy.
Patients enrolled in the trials will be randomized 1:1:1 to administrations every six months for four
years of anecortave acetate 15 mg, anecortave acetate 30 mg, or to a sham procedure. To date, approximately
170 patients have been enrolled, out of the total of 2,500 patients for the two studies.
In the study, anecortave acetate is being
evaluated for treatment in arresting the progression from dry AMD to exudative AMD in at-risk patients
using an important and clinically relevant measurement criteria, the incidence of sight-threatening
choroidal neovascularization, or CNV, said Dr. Russell. For this study, sight-threatening CNV is defined
as fluorescein angiographic evidence of new blood vessel growth under the retina within 2500 microns
of the center of the macula.
Physician-Initiated Trial with RETAANE and Triamcinolone
In addition to the phase III information
presented, investigator Jason S. Slakter, M.D., of the Manhattan Eye, Ear and Throat Hospital in New
York, presented study methods and initial data for a physician-initiated trial evaluating the safety
and efficacy of RETAANE 15 mg (anecortave acetate for depot suspension) and triamcinolone
acetate 4mg, or a combination of both, in patients with the wet form of AMD.* The protocol states that
eligible patients must have either subfoveal occult CNV with demonstrated disease progression, or subfoveal
minimally classic CNV. The first five patients in this study were treated with a combination of RETAANE
as the first line therapy and an intravitreal injection of triamcinolone acetate 4mg.
The results will serve as a preliminary
safety assessment of the combination therapy. When the initial five patients complete the month 3 visit,
another 60 patients will be enrolled in a masked study and assigned to receive either RETAANE
15 mg (anecortave acetate for depot suspension) and a sham injection of triamcinolone acetate 4 mg,
triamcinolone acetate 4mg and a sham administration of RETAANE , or a true combination
Given the nature of these two drugs, it
is possible that a combination of the agents may provide a synergistic effect, with the strong anti-permeability
effect of the steroid combined with the anti-angiogenic effect of anecortave acetate, said Dr. Slakter.
Age-related macular degeneration causes
damage to the macula the light-sensitive cells at the center of the retina at the back of the eye.
The macula is responsible for our ability to see with enough detail to read, drive, watch television
and perform other activities that require focused, straight-ahead vision, as well as providing information
that allows us to perceive colors; thus, allowing one to maintain independence in daily activities.
There are two types of AMD dry, or atrophic
or non-exudative, and wet, or exudative. Although the wet form of AMD constitutes only 10-15 percent
of all AMD cases, it is responsible for 90 percent of blindness attributable to this condition. Today,
wet AMD is the leading cause of blindness in industrialized nations in people over the age of 50, primarily
because there is a lack of effective treatments for the disease. Currently, there is no approved treatment
for dry AMD. The two currently approved treatments for wet AMD laser photocoagulation and photodynamic
therapy are appropriate for only a percentage of patients.
Anecortave acetate, the primary active ingredient
in RETAANE 15 mg (anecortave acetate for depot suspension), is an angiostatic cortisene
that inhibits the abnormal growth of blood vessels a process scientifically known as angiogenesis.
Angiostatic cortisenes were derived from the steroid class and engineered to remove chemical groups
responsible for unwanted glucocorticoid effects, such as the development of cataracts and elevated intraocular
pressure leading to glaucoma, while preserving angiostatic (or anti-neovascular) potency.
Some investigational therapies attempt to
block only one growth factor such as vascular endothelial growth factor (VEGF), thus still allowing
other growth factors, such as basic fibroblast growth factor (bFGF), to signal the endothelial cells
and commence the angiogenesis process. Angiostatic cortisenes are able to block signals from multiple
growth factors because they act downstream and independent of the initiating angiogenic stimuli thus
inhibiting angiogenesis subsequent to the angiogenic stimulation.
therapy for AMD that uses the unique delivery system of posterior juxtascleral depot (PJD). During the
procedure, RETAANE is drawn into a blunt-tipped, curved cannula and then delivered
in direct contact with the outer surface of the sclera without puncturing the eyeball. This method of
delivery for RETAANE avoids the risk of intraocular infection and retinal detachment,
the most common side effects associated with frequently injecting therapeutic agents directly into the
eye. RETAANE requires less frequent administration (once every six months) compared
to some other investigational angiogenesis inhibitors, which are injected into the eye as often as nine
to 12 times a year. According to an independent safety panel, no clinically relevant side effects were
associated with RETAANE or the PJD procedure.
Alcon, Inc. is the world s leading eye care
company. Alcon, which has been dedicated to the ophthalmic industry for over 50 years, develops, manufactures
and markets pharmaceuticals, surgical equipment and devices, contact lens solutions and other vision
care products that treat diseases, disorders and other conditions of the eye. Alcon has been conducting