The present Competitive Intelligence Report about Wet and Dry Age-Related Macular Degeneration (AMD) provides a competitor evaluation in the field of R&D projects for treatment of AMD as of February 2009.
Macular degeneration in the elderly (“age-related macular degeneration”, AMD) is a major cause of blindness. Its prevalence increases to 30% in patients 75 to 85 years of age. AMD occurs in two forms: dry and wet AMD. Central geographic atrophy, the “dry” form of advanced AMD, results from atrophy to the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye. While no treatment is available for this condition, vitamin supplements appear to slow the progression of dry macular degeneration and, in some patients, improve visual acuity. Neovascular or exudative AMD, the “wet” form of advanced AMD, causes vision loss due to abnormal blood vessel growth in the choriocapillaries, ultimately leading to blood and protein leakage below the macula. Bleeding, leaking, and scarring from these blood vessels eventually cause irreversible damage to the photoreceptors and rapid vision loss if left untreated.
It is only recently that new drugs have been approved for wet AMD which halt progression of the visual loss or even lead to improvement. The humanized antibody fragment ranibizumab (Lucentis) directed against vascular endothelial growth factor (VEGF) was developed by Genentech and Novartis has been approved in more than 70 countries worldwide since 2006 and posted record sales of US$ 1.76 bln in 2008.
The proven effectiveness and commercial success of the anti-VEGF treatment of wet AMD has encouraged many companies to develop new treatments of wet AMD based on the proven target VEGF as well as on other experimental approaches (anti-angiogenic, anti-proliferative, anti-inflammatory). More than 20 different approaches are in clinical development and more than 20 preclinical stage projecs are under evaluation for wet AMD. Among the projects are many biologics (antibodies, peptides, proteins, antisense, DNA, cells) facilitated by the topical (intravitreal administration). Small molecule approaches may confer the convenience of oral administration but efficacy still has to be demonstrated. Fewer projects are in clinical development for dry AMD, but the most prominent ones have reached advanced clinical testing, but definitive results are still lacking.
Wednesday, February 25, 2009
Tuesday, February 17, 2009
Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration.
Ophthalmology. 2008 Aug;115(8):e39-46.
Ahlers C, Golbaz I, Stock G, Fous A, Kolar S, Pruente C, Schmidt-Erfurth U.
Medical University of Vienna, Vienna, Austria.
PURPOSE: To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function.
DESIGN: Prospective noncomparative case series.
PARTICIPANTS: Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration.
METHODS: Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS).
MAIN OUTCOME MEASURES: Morphology and time course of different retinal and subretinal compartments.
RESULTS: High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation.
CONCLUSION: Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.
PMID: 18675694 [PubMed - indexed for MEDLINE]
Ahlers C, Golbaz I, Stock G, Fous A, Kolar S, Pruente C, Schmidt-Erfurth U.
Medical University of Vienna, Vienna, Austria.
PURPOSE: To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function.
DESIGN: Prospective noncomparative case series.
PARTICIPANTS: Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration.
METHODS: Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS).
MAIN OUTCOME MEASURES: Morphology and time course of different retinal and subretinal compartments.
RESULTS: High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation.
CONCLUSION: Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.
PMID: 18675694 [PubMed - indexed for MEDLINE]
Thursday, February 12, 2009
Serum Cystatin C Level, Kidney Disease Markers, and Incidence of Age-Related Macular Degeneration
The Beaver Dam Eye Study
Ronald Klein, MD, MPH; Michael D. Knudtson, MS; Kristine E. Lee, MS; Barbara E. K. Klein, MD, MPH
Arch Ophthalmol. 2009;127(2):193-199.
Objective
To examine the associations of the serum cystatin C level and chronic kidney disease with the incidence of age-related macular degeneration (AMD) over 15 years.
Methods
In this population-based cohort study of 4926 individuals aged 43 to 86 years at baseline, 3779 participated in 1 or more follow-up examinations. Age-related macular degeneration was determined by grading photographs of the macula. Individuals were defined as having mild or moderate to severe chronic kidney disease based on a value of more than 45 mL/min/1.73 m2 to 60 mL/min/1.73 m2 or less and 45 mL/min/1.73 m2 or less, respectively, according to the Modification of Diet in Renal Disease Study equation.
Results
While controlling for age and other risk factors, the level of serum cystatin C at baseline was associated with the incidence of early AMD (odds ratio per log standard deviation [95% confidence interval], 1.16 [1.01-1.35]) and exudative AMD (1.42 [1.03-1.96]) but not geographic atrophy (0.89 [0.56-1.41]) or progression of AMD (1.02 [0.88-1.18]). Mild chronic kidney disease was associated with the 15-year cumulative incidence of early AMD (odds ratio per log standard deviation, 1.36 [95% confidence interval, 1.00-1.86]) but not the incidence of other AMD end points.
Conclusion
There is a relationship between the level of serum cystatin C and chronic kidney disease with the incidence of AMD. The underlying biological processes remain to be determined.
Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
Ronald Klein, MD, MPH; Michael D. Knudtson, MS; Kristine E. Lee, MS; Barbara E. K. Klein, MD, MPH
Arch Ophthalmol. 2009;127(2):193-199.
Objective
To examine the associations of the serum cystatin C level and chronic kidney disease with the incidence of age-related macular degeneration (AMD) over 15 years.
Methods
In this population-based cohort study of 4926 individuals aged 43 to 86 years at baseline, 3779 participated in 1 or more follow-up examinations. Age-related macular degeneration was determined by grading photographs of the macula. Individuals were defined as having mild or moderate to severe chronic kidney disease based on a value of more than 45 mL/min/1.73 m2 to 60 mL/min/1.73 m2 or less and 45 mL/min/1.73 m2 or less, respectively, according to the Modification of Diet in Renal Disease Study equation.
Results
While controlling for age and other risk factors, the level of serum cystatin C at baseline was associated with the incidence of early AMD (odds ratio per log standard deviation [95% confidence interval], 1.16 [1.01-1.35]) and exudative AMD (1.42 [1.03-1.96]) but not geographic atrophy (0.89 [0.56-1.41]) or progression of AMD (1.02 [0.88-1.18]). Mild chronic kidney disease was associated with the 15-year cumulative incidence of early AMD (odds ratio per log standard deviation, 1.36 [95% confidence interval, 1.00-1.86]) but not the incidence of other AMD end points.
Conclusion
There is a relationship between the level of serum cystatin C and chronic kidney disease with the incidence of AMD. The underlying biological processes remain to be determined.
Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
Thursday, February 5, 2009
Age-Related Eye Disease Study (AREDS) Examines Macular Degeneration Risk Related to Cataract Surgery
Age-related macular degeneration (AMD) and cataract are leading causes of visual impairment in the United States. Both are related to aging, and they share other risk factors, but it has been unclear whether a direct causal link might be involved. Several large epidemiological studies had raised concern that cataract surgery might accelerate AMD progress and threaten vision. To address this concern, Emily Y. Chew, MD, of the National Eye Institute, and colleagues analyzed data for a cohort of participants in the Age-Related Eye Disease Study (AREDS). This cohort is the only large prospective study in which the severity of AMD was documented before and after cataract surgery and which included more than five years of in-depth participant follow-up.
AMD causes changes in the retina, the light-sensitive tissue that focuses images at the back of the eye, and severe AMD leads to loss of central vision. Cataract is cloudiness or opacity in the eye's lens that interferes with the clear focus of images on the retina.
AREDS researchers concluded there was little evidence that cataract surgery had a negative effect on progression to advanced AMD. ?These data may provide some reassurance to patients with AMD who are considering cataract surgery,? Dr. Chew said.
The primary purpose of the AREDS multicenter controlled randomized clinical trial was to assess whether antioxidant and mineral supplements affect progress to advanced AMD and development of cataracts. The cohort study included 4,577 participants (8,050 eyes) aged 55 through 81 at enrollment; it compared the risk of advanced AMD in patients who had cataracts removed versus the risk for those who did not have the surgery. All participants took either antioxidant/mineral supplements or placebos. Study eyes were examined every six months over five or more years. One analysis compared AMD progression in matched pairs of eyes, where one eye had cataract surgery after baseline but before developing advanced AMD, and the paired eye did not have cataract surgery. Matched pairs were determined based on similar risk factors for AMD, assigned antioxidant or placebo treatment, baseline AMD category, person?s age, and other factors. Results of the matched pair analysis and of two other standard analytical models revealed no consistent pattern of accelerated AMD progression after cataract surgery.
Several factors may explain the divergent conclusions reached by AREDS and the earlier studies. The most likely cause would be that earlier studies had unintended biases or confounding variables. Also, techniques of cataract surgery and lens replacement have changed over time, and AREDS participant surgeries were performed more recently than those tracked in the combined-population studies. A significant number of subjects in earlier studies did not have lens replacement after cataract extraction, while AREDS participants were likely to have had ultraviolet-B light blocking lenses inserted, which may have protected their maculae and decreased AMD risk.
AMD causes changes in the retina, the light-sensitive tissue that focuses images at the back of the eye, and severe AMD leads to loss of central vision. Cataract is cloudiness or opacity in the eye's lens that interferes with the clear focus of images on the retina.
AREDS researchers concluded there was little evidence that cataract surgery had a negative effect on progression to advanced AMD. ?These data may provide some reassurance to patients with AMD who are considering cataract surgery,? Dr. Chew said.
The primary purpose of the AREDS multicenter controlled randomized clinical trial was to assess whether antioxidant and mineral supplements affect progress to advanced AMD and development of cataracts. The cohort study included 4,577 participants (8,050 eyes) aged 55 through 81 at enrollment; it compared the risk of advanced AMD in patients who had cataracts removed versus the risk for those who did not have the surgery. All participants took either antioxidant/mineral supplements or placebos. Study eyes were examined every six months over five or more years. One analysis compared AMD progression in matched pairs of eyes, where one eye had cataract surgery after baseline but before developing advanced AMD, and the paired eye did not have cataract surgery. Matched pairs were determined based on similar risk factors for AMD, assigned antioxidant or placebo treatment, baseline AMD category, person?s age, and other factors. Results of the matched pair analysis and of two other standard analytical models revealed no consistent pattern of accelerated AMD progression after cataract surgery.
Several factors may explain the divergent conclusions reached by AREDS and the earlier studies. The most likely cause would be that earlier studies had unintended biases or confounding variables. Also, techniques of cataract surgery and lens replacement have changed over time, and AREDS participant surgeries were performed more recently than those tracked in the combined-population studies. A significant number of subjects in earlier studies did not have lens replacement after cataract extraction, while AREDS participants were likely to have had ultraviolet-B light blocking lenses inserted, which may have protected their maculae and decreased AMD risk.
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