The pharmaceutical giant Genzyme has started a clinical trial to see whether a drug to treat macular generation could be delivered via long-lasting gene therapy rather than monthly injections.
Eye colors: Drusen, the yellow flecks in this image of the retina, are common in people with age-related macular degeneration. These flecks are made up of proteins involved in the part of the immune system called the complement system, which has also been implicated in the disease by genetic studies.
A drug called Lucentis, made by Genetech, has proved effective at treating the wet form of age-related macular degeneration, which can lead to blindness. Some 200,000 Americans a year are diagnosed with the disease. But Lucentis has to be injected into the eye every month or two, a burden for patients and doctors.
Lucentis binds to and neutralizes a wound-healing growth factor known as VEGF. This binding action stalls the excess growth of blood vessels in the eye that characterizes age-related macular degeneration. Genzyme's gene therapy drug, officially called AAV2-sFLT01, would insinuate itself into the patient's retinal cell to produce the same VEGF-binding protein as Lucentis over far longer periods--up to several years.
A phase 1 clinical trial of Genzyme's gene therapy treatment began at the end of May. Three patients received the treatment, according to Sam Wadsworth, a Genzyme group vice president in charge of gene and cell therapy. Preliminary results should be available in about a year.
The trial is one of a handful worldwide seeking to prove the effectiveness of gene therapy for eye diseases. The Genzyme trial also involves using new type of virus as the delivery mechanism. Early results of a federally funded trial to deliver normal-functioning genes to patients with a rare retinal disease known as type 2 leber congenital amaurosis, or LCA, have confirmed that this "viral vector" has merit for eye treatments, several researchers say.
The LCA trials "demonstrated success both in terms of safety and ability to introduce the gene and have efficacy and success," said Jeffrey S. Heier, an assistant professor at Tufts University School of Medicine and director of retinal research at Ophthalmic Consultants of Boston, a private practice group, who is involved in the Genzyme research. "This study is taking the virus vector that they used, and [Genzyme has] taken what has really been the success of the anti-VEGF story and they've packaged the two together."
Eyes have been an early target for gene therapy because they are small--meaning they require relatively little active dose, they are self-contained, and because the tools of eye surgery have advanced enough to make the treatments possible. The drug has to be delivered to the retina, a thin film lining the inner wall of the eye. Instrumentation has improved in recent years to allow injections through the retina without piercing it, said Shalesh Kaushal, chairman of ophthalmology at University of Massachusetts Memorial Medical Center and UMass Medical School.
To Kaushal, who is involved in the Genzyme study as well as the LCA research, the big challenge will be broadening the use of gene therapy to dozens more diseases, and using that understanding to eventually reach beyond the eye. "If one could understand those fundamental cellular, biochemical events and identify targets, you might have the chance to treat many diseases with a single gene-therapy construct," Kaushal said.
Earlier gene therapy programs used a type of virus called adenovirus to target genes, but both the LCA and Genzyme trials are using adeno-associated virus, which is far less inflammatory and which expresses itself over longer periods than adenovirus, therefore making the treatment last longer, Wadsworth said. Viruses are used to deliver gene therapies because they are adept at getting through cell walls.
VEGF is involved in vascular cell growth throughout the body, and its expression increases in the presence of a wound. Studies have shown that with Lucentis, virtually all the VEGF-binding protein stays within the eye, and does not significantly affect VEGF levels elsewhere in the body, Wadsworth says. Genzyme's drug will provide even lower levels of the VEGF-binding protein, so it's expected that the drug will not have any adverse affects throughout the body, he said.
The trick will be getting the cells to produce enough VEGF-binding protein to help patients, said Peter Campochiaro, a professor at the Wilmer Eye Institute at Johns Hopkins Medicine, who is involved in the research. In addition to establishing safety, the current phase 1 trial will explore four different doses of the study
Showing posts with label biomarker. Show all posts
Showing posts with label biomarker. Show all posts
Friday, July 16, 2010
Wednesday, July 7, 2010
Tyrosine Kinase inhibitor shows promise for AMD treatment
A new study finds that inhibition of CXCR4 may be useful in preventing neovascularization but does not appear to have an effect on already established angiogenesis, whereas a multiple receptor tyrosine kinase inhibitor (SU14813) reduced the size of previously formed lesions.
Endothelial precursor cells (EPCs) derived from hematopoietic stem cells (HSCs) have been shown to contribute to choroidal neovascularization (CNV) by signaling through the SDF-1 and its receptor, known as CXCR4. Hematopoietic stem cells are implicated in the formation of new pathologic vessels observed in wet AMD. Recruitment of endothelial precursor cells to the site of neovascularization is mediated, in part, by the chemokine SDF-1, and its receptor, CXCR4. CXCR4 is a G-protein-coupled receptor found on lymphocytes, monocytes, hematopoietic, endothelial progenitor cells, and mature endothelial cells.
Methods and Results
CNV in rats was generated by focal rupture of Bruch's membrane with an 810-nm diode laser. In the prevention mode, a CXCR4 antagonist (AMD3100) was delivered via an osmotic pump 1 day after laser induction. In the intervention mode, AMD3100 delivery commenced 14 days after laser induction. Inhibition of CXCR4 was determined through leukocyte and SDF-1 actin polymerization blood biomarker assays. Leakage was assessed by fluorescein angiography, and CNV lesion size was quantified after isolectin B4 endothelial cell staining. SU14813, an anti-VEGFR, PDGFR-beta, KIT, and FLT3 inhibitor, was also assessed in an intervention study protocol.
Related News
CCR3 is a target for AMD diagnosis and therapy
Integrin α5β1 inhibitor JSM6427 combats CNV in animal study
Stem cells show promise to restore vision
Inhibition of CXCR4 was demonstrated by an increase in the number of blood leukocytes, and diminished SDF-1 induced actin polymerization in whole blood. CNV leakage and neovascularization were inhibited when the dose regimen was initiated 1 day after laser-induced CNV induction. AMD3100 did not show efficacy when administered 14 days after lasering. Treatment with SU14813 significantly decreased CNV leakage and lesion size in an intervention modality.
Discussion and Conclusions
In this study, CXCR4 inhibition was efficacious in the prevention of CNV, but failed to reduce choroidal leakage and angiogenesis in the intervention modality. This finding suggests that therapies targeting the SDF-1/CXCR4 axis may be beneficial in blocking the induction of ocular neoangiogenesis, but are unlikely to reduce already established angiogenesis.
There is strong evidence that CXCR4 inhibition disrupts the recruitment of endothelial precursor cells (EPCs) to sites of angiogenesis, most likely the major mechanism leading to efficacy in the prevention model.
In addition to suppressing CNV, CXCR4 inhibition reduced choroidal vascular leakage in the prevention modality (but not in the intervention modality). It is not known whether CXCR4 inhibition decreases leakage directly or as a secondary effect of the reduction of the angiogenic vessel area.
The observation that CXCR4 inhibition did not decrease choroidal leakage or angiogenic lesion size in the intervention modality suggests that after a 2-week generation of laser-induced CNV, there is limited, if any, contribution of EPC cells to the already established vessels
A multiple receptor tyrosine kinase (RTK) inhibitor may still be an effective monotherapy, as SU14813 reduced the size of previously formed lesions. In treatment mode, both leakage and angiogenesis decreased even after the pathologic effect was given 14 days to fully establish before drug intervention. This study suggests that blockade of the VEGF receptor is an effective alternative method of inhibiting the VEGF pathway compared to conventional anti-VEGF strategies.
SU14813 is a small molecule with broad target RTK selectivity, inhibiting the VEGF receptor (VEGFR), PDGFR-β, KIT, and FLT3. Although the primary mechanism that reduces preexisting angiogenesis and leakage is the blockade of the central VEGF pathway, the additional inhibition of PDGFR-β may augment efficacy in this model over single anti-VEGFR agents.
The investigators conclude that inhibition of CXCR4 may be useful in preventing neovascularization but does not appear to have an effect on already established angiogenesis. A multiple receptor tyrosine kinase inhibitor (SU14813) approach shows promise for the treatment of wet age-related macular degeneration.
Endothelial precursor cells (EPCs) derived from hematopoietic stem cells (HSCs) have been shown to contribute to choroidal neovascularization (CNV) by signaling through the SDF-1 and its receptor, known as CXCR4. Hematopoietic stem cells are implicated in the formation of new pathologic vessels observed in wet AMD. Recruitment of endothelial precursor cells to the site of neovascularization is mediated, in part, by the chemokine SDF-1, and its receptor, CXCR4. CXCR4 is a G-protein-coupled receptor found on lymphocytes, monocytes, hematopoietic, endothelial progenitor cells, and mature endothelial cells.
Methods and Results
CNV in rats was generated by focal rupture of Bruch's membrane with an 810-nm diode laser. In the prevention mode, a CXCR4 antagonist (AMD3100) was delivered via an osmotic pump 1 day after laser induction. In the intervention mode, AMD3100 delivery commenced 14 days after laser induction. Inhibition of CXCR4 was determined through leukocyte and SDF-1 actin polymerization blood biomarker assays. Leakage was assessed by fluorescein angiography, and CNV lesion size was quantified after isolectin B4 endothelial cell staining. SU14813, an anti-VEGFR, PDGFR-beta, KIT, and FLT3 inhibitor, was also assessed in an intervention study protocol.
Related News
CCR3 is a target for AMD diagnosis and therapy
Integrin α5β1 inhibitor JSM6427 combats CNV in animal study
Stem cells show promise to restore vision
Inhibition of CXCR4 was demonstrated by an increase in the number of blood leukocytes, and diminished SDF-1 induced actin polymerization in whole blood. CNV leakage and neovascularization were inhibited when the dose regimen was initiated 1 day after laser-induced CNV induction. AMD3100 did not show efficacy when administered 14 days after lasering. Treatment with SU14813 significantly decreased CNV leakage and lesion size in an intervention modality.
Discussion and Conclusions
In this study, CXCR4 inhibition was efficacious in the prevention of CNV, but failed to reduce choroidal leakage and angiogenesis in the intervention modality. This finding suggests that therapies targeting the SDF-1/CXCR4 axis may be beneficial in blocking the induction of ocular neoangiogenesis, but are unlikely to reduce already established angiogenesis.
There is strong evidence that CXCR4 inhibition disrupts the recruitment of endothelial precursor cells (EPCs) to sites of angiogenesis, most likely the major mechanism leading to efficacy in the prevention model.
In addition to suppressing CNV, CXCR4 inhibition reduced choroidal vascular leakage in the prevention modality (but not in the intervention modality). It is not known whether CXCR4 inhibition decreases leakage directly or as a secondary effect of the reduction of the angiogenic vessel area.
The observation that CXCR4 inhibition did not decrease choroidal leakage or angiogenic lesion size in the intervention modality suggests that after a 2-week generation of laser-induced CNV, there is limited, if any, contribution of EPC cells to the already established vessels
A multiple receptor tyrosine kinase (RTK) inhibitor may still be an effective monotherapy, as SU14813 reduced the size of previously formed lesions. In treatment mode, both leakage and angiogenesis decreased even after the pathologic effect was given 14 days to fully establish before drug intervention. This study suggests that blockade of the VEGF receptor is an effective alternative method of inhibiting the VEGF pathway compared to conventional anti-VEGF strategies.
SU14813 is a small molecule with broad target RTK selectivity, inhibiting the VEGF receptor (VEGFR), PDGFR-β, KIT, and FLT3. Although the primary mechanism that reduces preexisting angiogenesis and leakage is the blockade of the central VEGF pathway, the additional inhibition of PDGFR-β may augment efficacy in this model over single anti-VEGFR agents.
The investigators conclude that inhibition of CXCR4 may be useful in preventing neovascularization but does not appear to have an effect on already established angiogenesis. A multiple receptor tyrosine kinase inhibitor (SU14813) approach shows promise for the treatment of wet age-related macular degeneration.
Sunday, May 10, 2009
New Medical Study Establishes First-Ever Long-Term Benefits for Macular Degeneration Sufferers Using Macular Health Vitamin Supplement
New Medical Study Establishes First-Ever Long-Term Benefits for Macular Degeneration Sufferers Using Macular Health Vitamin Supplement
Eye disease product has the potential to preserve vision for millions
BIRMINGHAM, Ala., April 28 /PRNewswire/ -- As many as 17.8 million people will suffer from age-related macular degeneration (AMD) by 2050 and 1.57 million will be blind from the disease, according to the U.S. Centers for Disease Control and Prevention. However, a new medical study by a group of retina specialists at the Callahan Eye Foundation Hospital at the University of Alabama Birmingham (UAB) indicates that with the use of the Macular Health vitamin supplement there is a way to reduce these numbers and potentially preserve the vision of millions.
The second phase of the Multifocal Electroretinogram (MERG) study recently revealed that patients suffering from AMD experienced long-term benefits from taking Macular Health, a special combination of supplemental vitamins, minerals and carotenoids. Phase I of the MERG study, completed in 2005, confirmed an average of 16 percent improvement in vision after taking Macular Health for only 12 weeks. Phase II measured the vision function of the same patients two years later and found an average improvement in vision of 17 percent.
"The outcome of this study is extremely encouraging for sufferers of age-related macular degeneration," says John O. Mason, III, MD, researcher and retinal specialist at the Callahan Eye Foundation Hospital. "These new findings prove that Macular Health can slow vision loss and actually improve vision function over time."
MERG testing was used to gauge the vision of AMD patients before and after using the Macular Health supplement. The test results of patients taking Macular Health were compared to results of a control group that did not take the supplement. Phase II of the study was accepted by the Association for Research and Vision in Ophthalmology (ARVO) for poster presentation. Mason and a team of retina specialists will continue to monitor study participants to evaluate improvement in eye health and vision with the use of Macular Health.
Jeffery McAnnally, President of Macular Health, LLC, says, "On behalf of the Macular Health Company, I am pleased to share this additional proof of Macular Health's effectiveness. Not only is Macular Health the most affordable product of its kind on the market today, it is the easiest to take."
An estimated 9 million people currently suffer from AMD, and one-third of adults over 70 are afflicted with this incurable disease. AMD is the leading cause of blindness in Americans 50 years of age and older. AMD is a breakdown of the macula of the eye that typically occurs during the aging process. Damage of the macula increases the difficulty of seeing fine details and even faces clearly.
To learn more about age-related macular degeneration or the Macular Health vitamin supplement, visit www.macularhealth.com. To speak with John O. Mason, III, MD, please contact Julie Ward at 205.503.5955 or julie@styleadvertising.com.
Website: http://www.macularhealth.com/
Eye disease product has the potential to preserve vision for millions
BIRMINGHAM, Ala., April 28 /PRNewswire/ -- As many as 17.8 million people will suffer from age-related macular degeneration (AMD) by 2050 and 1.57 million will be blind from the disease, according to the U.S. Centers for Disease Control and Prevention. However, a new medical study by a group of retina specialists at the Callahan Eye Foundation Hospital at the University of Alabama Birmingham (UAB) indicates that with the use of the Macular Health vitamin supplement there is a way to reduce these numbers and potentially preserve the vision of millions.
The second phase of the Multifocal Electroretinogram (MERG) study recently revealed that patients suffering from AMD experienced long-term benefits from taking Macular Health, a special combination of supplemental vitamins, minerals and carotenoids. Phase I of the MERG study, completed in 2005, confirmed an average of 16 percent improvement in vision after taking Macular Health for only 12 weeks. Phase II measured the vision function of the same patients two years later and found an average improvement in vision of 17 percent.
"The outcome of this study is extremely encouraging for sufferers of age-related macular degeneration," says John O. Mason, III, MD, researcher and retinal specialist at the Callahan Eye Foundation Hospital. "These new findings prove that Macular Health can slow vision loss and actually improve vision function over time."
MERG testing was used to gauge the vision of AMD patients before and after using the Macular Health supplement. The test results of patients taking Macular Health were compared to results of a control group that did not take the supplement. Phase II of the study was accepted by the Association for Research and Vision in Ophthalmology (ARVO) for poster presentation. Mason and a team of retina specialists will continue to monitor study participants to evaluate improvement in eye health and vision with the use of Macular Health.
Jeffery McAnnally, President of Macular Health, LLC, says, "On behalf of the Macular Health Company, I am pleased to share this additional proof of Macular Health's effectiveness. Not only is Macular Health the most affordable product of its kind on the market today, it is the easiest to take."
An estimated 9 million people currently suffer from AMD, and one-third of adults over 70 are afflicted with this incurable disease. AMD is the leading cause of blindness in Americans 50 years of age and older. AMD is a breakdown of the macula of the eye that typically occurs during the aging process. Damage of the macula increases the difficulty of seeing fine details and even faces clearly.
To learn more about age-related macular degeneration or the Macular Health vitamin supplement, visit www.macularhealth.com. To speak with John O. Mason, III, MD, please contact Julie Ward at 205.503.5955 or julie@styleadvertising.com.
Website: http://www.macularhealth.com/
Sunday, April 19, 2009
New Drug May Help Treat, Reverse Advanced Macular Degeneration
Apr 13, 2009
Reporter: CBS News
Email Address: news@kbtx.com
As the baby boomers age and live longer, a severe sight problem called Macular Degeneration is becoming more common.
But, there are new treatments to help the condition that can lead to blindness.
Sylvia Moore was diagnosed with macular degeneration three years ago.
"If I look straight ahead at somebody's face, I don't see them at all, you'd see a blank spot, a black spot," says Moore of the disease.
Macular Degeneration is most common in seniors.
It happens when blood vessels in the back of the eye start leaking and is the leading cause of blindness in people over 65.
The good news is doctors now have more weapons than ever to fight the condition, and in some cases even reverse it.
When it's caught early, vitamin therapy can slow down the progression of macular degeneration, and in some cases laser surgery can halt vision loss.
But the latest treatment is a drug that's injected directly into the eye.
The medication targets the abnormal blood vessels leading to its shutdown and hopefully to the improvement in vision.
Moore has been getting the injections for three months and is already seeing a difference.
"Its scary when you see a needle coming at you but it doesn't hurt.... I'd rather have that than blindness," Moore says.
A new study predicts some 9 million americans will be diagnosed with macular degeneration next year.
That number is expected to double in the next 40 years.
Apr 13, 2009
Reporter: CBS News
Email Address: news@kbtx.com
As the baby boomers age and live longer, a severe sight problem called Macular Degeneration is becoming more common.
But, there are new treatments to help the condition that can lead to blindness.
Sylvia Moore was diagnosed with macular degeneration three years ago.
"If I look straight ahead at somebody's face, I don't see them at all, you'd see a blank spot, a black spot," says Moore of the disease.
Macular Degeneration is most common in seniors.
It happens when blood vessels in the back of the eye start leaking and is the leading cause of blindness in people over 65.
The good news is doctors now have more weapons than ever to fight the condition, and in some cases even reverse it.
When it's caught early, vitamin therapy can slow down the progression of macular degeneration, and in some cases laser surgery can halt vision loss.
But the latest treatment is a drug that's injected directly into the eye.
The medication targets the abnormal blood vessels leading to its shutdown and hopefully to the improvement in vision.
Moore has been getting the injections for three months and is already seeing a difference.
"Its scary when you see a needle coming at you but it doesn't hurt.... I'd rather have that than blindness," Moore says.
A new study predicts some 9 million americans will be diagnosed with macular degeneration next year.
That number is expected to double in the next 40 years.
Saturday, April 11, 2009
Eye 'compensates for blind spot'
Eye 'compensates for blind spot'
Eye Peripheral vision is retained
Partially sighted and registered blind people can be taught to read and see faces again using the undamaged parts of their eyes, say experts.
When only the central vision is lost, as with the leading cause of blindness, age-related macular degeneration, peripheral vision remains intact.
And patients can be taught to exploit this, the Macular Disease Society says.
It has developed a training scheme and is calling for professionals to adopt the system across the UK.
The macula is a small area of the retina at the back of the eye made up of specialist cells which process central vision as well as the fine detail of what we see.
Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good
Tom Bremridge
Macular Disease Society
People with macular degeneration rarely go totally blind but even those with a relatively mild version of the disease cannot drive and have difficulty reading, recognising faces and watching television.
But studies show people can be taught to use their peripheral vision to fill in the gaps, using "eccentric viewing" and "steady eye techniques".
When someone with central vision loss looks directly at an object it may disappear, go faint, blur or distort. But when they look above, below or to one side of it, they see it more clearly.
Blind spots
Eccentric viewing helps people find exactly where to focus their gaze to make their vision better.
Once this position is identified, they can be taught how to read again using the steady eye technique.
Instead of moving the eyes from left to right to read a sentence, the person should keep their eyes completely still and move the text to the left so that each word in turn moves into the area of best vision.
All UK patients with central vision loss should have the opportunity to try eccentric viewing
Mr Winfried Amoaku
Royal College of Ophthalmologists
Macular Disease Society chief executive Tom Bremridge said: "Eccentric viewing works by making the most of vision that remains.
"Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good.
"We have 86 volunteer trainers, all with central vision loss themselves, who have trained more than 310 people in their own communities, and our waiting list of nearly 1,200 people grows every day.
"We are keen that other service providers - social services, private practitioners and primary care trusts - now take up the baton."
Mr Winfried Amoaku, of the Royal College of Ophthalmologists, said eccentric viewing could help some patients with central vision loss "cope with everyday tasks such as identifying coins while out shopping, watching television and reading".
"The trouble is, we don't know who will benefit until they have tried the training.
"All UK patients with central vision loss should have the opportunity to try eccentric viewing techniques to see if they can benefit," he said.
Marek Karas, of the Royal National Institute of Blind People, also supported the research advances.
"Although there is still ongoing discussion among experts over the best form of training for this type of therapy, we welcome with interest these latest developments."
Between 25 and 30 million people worldwide have macular degeneration. But as the population ages, this figure will rise.
It is estimated that the number of people affected will triple by 2025.
Eye Peripheral vision is retained
Partially sighted and registered blind people can be taught to read and see faces again using the undamaged parts of their eyes, say experts.
When only the central vision is lost, as with the leading cause of blindness, age-related macular degeneration, peripheral vision remains intact.
And patients can be taught to exploit this, the Macular Disease Society says.
It has developed a training scheme and is calling for professionals to adopt the system across the UK.
The macula is a small area of the retina at the back of the eye made up of specialist cells which process central vision as well as the fine detail of what we see.
Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good
Tom Bremridge
Macular Disease Society
People with macular degeneration rarely go totally blind but even those with a relatively mild version of the disease cannot drive and have difficulty reading, recognising faces and watching television.
But studies show people can be taught to use their peripheral vision to fill in the gaps, using "eccentric viewing" and "steady eye techniques".
When someone with central vision loss looks directly at an object it may disappear, go faint, blur or distort. But when they look above, below or to one side of it, they see it more clearly.
Blind spots
Eccentric viewing helps people find exactly where to focus their gaze to make their vision better.
Once this position is identified, they can be taught how to read again using the steady eye technique.
Instead of moving the eyes from left to right to read a sentence, the person should keep their eyes completely still and move the text to the left so that each word in turn moves into the area of best vision.
All UK patients with central vision loss should have the opportunity to try eccentric viewing
Mr Winfried Amoaku
Royal College of Ophthalmologists
Macular Disease Society chief executive Tom Bremridge said: "Eccentric viewing works by making the most of vision that remains.
"Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good.
"We have 86 volunteer trainers, all with central vision loss themselves, who have trained more than 310 people in their own communities, and our waiting list of nearly 1,200 people grows every day.
"We are keen that other service providers - social services, private practitioners and primary care trusts - now take up the baton."
Mr Winfried Amoaku, of the Royal College of Ophthalmologists, said eccentric viewing could help some patients with central vision loss "cope with everyday tasks such as identifying coins while out shopping, watching television and reading".
"The trouble is, we don't know who will benefit until they have tried the training.
"All UK patients with central vision loss should have the opportunity to try eccentric viewing techniques to see if they can benefit," he said.
Marek Karas, of the Royal National Institute of Blind People, also supported the research advances.
"Although there is still ongoing discussion among experts over the best form of training for this type of therapy, we welcome with interest these latest developments."
Between 25 and 30 million people worldwide have macular degeneration. But as the population ages, this figure will rise.
It is estimated that the number of people affected will triple by 2025.
Monday, March 30, 2009
Positive Results from Neurotech's NT-501 Phase 2 Dry AMD
Positive Results from Neurotech's NT-501 Phase 2 Dry AMD (Geographic Atrophy) Study Demonstrate Proof of Concept
Virtual Clinical Trials
Global Clinical Development Collaboration Solutions
www.trialinteractive.com
Validate Company's ECT Technology and Support Initiation of Pivotal Studies
LINCOLN, R.I.--(BUSINESS WIRE)--Mar 26, 2009 - Neurotech Pharmaceuticals, Inc., today announced that the Company's lead product candidate, NT-501, substantially slowed the loss of vision in a Phase 2 clinical trial in subjects with dry age-related macular degeneration (AMD) involving geographic atrophy (GA). GA is a condition that destroys sharp central vision, often resulting in serious vision loss to one or both eyes. There are currently no approved treatments for dry AMD. In the study, the high dose of NT-501 stabilized best corrected visual acuity (BCVA) at 12-months, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group.
NT-501 is an intraocular implant that consists of human cells that have been genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is delivered directly to the back of the eye in a controlled, continuous basis by means of the Company's proprietary Encapsulated Cell Technology (ECT) platform, thereby bypassing the blood-retinal barrier and overcoming a major obstacle in the treatment of retinal disease.
The Phase 2 study is a multi-centered, randomized, double-masked, sham-controlled study of 51 subjects with GA. Patients received either a high or low dose NT-501 implant or a sham treatment in one eye only and were assessed for changes in BCVA. BCVA was measured by an Electronic Visual Acuity Tester (EVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Patients were also evaluated for an increase in BCVA. However, no increase was observed, likely due to existing photoreceptor damage. There were no NT-501 associated serious adverse events reported and both NT-501 and the surgical procedure were well-tolerated.
“The favorable functional visual acuity results for patients at this advanced stage of dry AMD are particularly promising due to the significant prevalence of the condition, its serious impact on quality of life and the current unmet medical need for effective therapy," stated Dr. George A. Williams, a study investigator and Professor and Chair of the Department of Ophthalmology at William Beaumont Hospital and the Oakland University William Beaumont School of Medicine in Royal Oak, MI.
The strong trend in visual acuity stabilization at 12 months was preceded by a dose-dependent, statistically significant (p<0.001 and p=0.013 for high and low dose, respectively) increase in retinal thickness as measured by optical coherence tomography (OCT) that was observed as early as 4 months post-implantation. The observed structural change is consistent with preclinical studies of NT-501 in which CNTF was shown to increase the thickness of the retina and the outer nuclear layer of photoreceptors responsible for vision. This increase in retinal thickness may be responsible for photoreceptor rescue and protection as observed in numerous animal models of retinal degeneration.
“Based on the increase in retinal thickness observed in this study it appears that CNTF may be exhibiting a biological effect on retinal photoreceptors as has been observed previously in animal studies,” said Dr. Paul Sieving, Director of the National Eye Institute and Principal Investigator of Neurotech's Phase 1 study of NT-501 in retinitis pigmentosa.
“We believe the anatomical changes observed in patients treated with NT-501 have led to the emergence of a clinically meaningful visual acuity benefit for patients with geographic atrophy,” commented Ted Danse, President and Chief Executive Officer of Neurotech. “NT-501 may provide a much needed treatment option for these patients and we intend to discuss these data and a pivotal trial design with the FDA.”
“We are very pleased that the outcome of this trial has shown such promise for patients with dry AMD involving geographic atrophy and are proud of our long-term support for this unique, breakthrough technology,” stated Stephen Rose, PhD, Chief Research Officer, Foundation Fighting Blindness.
Five devices from this trial have been explanted 12 months following implantation and all have been found to have uniformly healthy, viable cells that continue to produce therapeutic levels of CNTF. This is consistent with data from multiple trials of NT-501 in which, to date, 23 devices have been explanted between 12 and 18 months following implantation and all devices have contained healthy, viable CNTF-producing cells.
“We also believe the positive results of this study and long-term cell viability validate our ECT platform and support a breakthrough opportunity to advance long-term, well-tolerated treatments for patients facing chronic sight-stealing retinal diseases. As such, we are developing our second product utilizing the ECT platform to address a well-validated target, anti-VEGF therapy for wet AMD, that has the potential to provide a one-time administration for a 12 to 18 month period versus the current wet AMD treatment regimen that requires monthly injections with routine patient monitoring,” concluded Danse.
Data from the Phase 2 dry AMD/GA trial will be presented at the Retinal Physician Symposium on March 27, 2009 in the Bahamas, at IBC's 5th International Ocular Angiogenesis & Retinal Degeneration conference on March 31, 2009 in Las Vegas, at the Advanced Vitreoretinal Techniques and Technologies meeting on April 24, 2009 in Las Vegas and at the Association for Research in Vision and Ophthalmology (ARVO) meeting on May 6, 2009 in Ft. Lauderdale.
About Dry AMD/Geographic Atrophy
Age-related macular degeneration (AMD) is a chronic progressive disease of the macula that results in the loss of central vision. It is the leading cause of blindness in elderly people in the developed world. There are two forms of AMD•dry and wet. Dry AMD is the most common form of AMD representing approximately 90% of all AMD cases. In its advanced stages dry AMD can lead to the degeneration of photoreceptors and retinal pigment epithelial cells, a chronic condition called geographic atrophy (GA). There are currently no approved GA therapies for the nearly 1 million individuals affected in the United States.
About NT-501
Neurotech's lead product, NT-501, consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. NT-501 is designed to continually deliver a therapeutic dose of CNTF into the back of the eye.
About Encapsulated Cell Technology
Neurotech's core technology platform is Encapsulated Cell Technology (ECT), a unique technology that allows for the long-term, sustained delivery of therapeutic factors to the back of the eye. ECT implants consist of cells that have been genetically modified to produce a specific therapeutic protein and are encapsulated in a semi-permeable hollow fiber membrane. The diffusive characteristics of the hollow fiber membrane are designed to promote long-term cell survival by allowing the influx of oxygen and nutrients while simultaneously preventing direct contact of the encapsulated cells with the cellular and molecular elements of the immune system. The cells continuously produce the therapeutic protein which diffuses out of the implant at the target site. ECT thereby enables the controlled, continuous delivery of therapeutic factors directly to the retina, bypassing the blood-retina barrier.
About Neurotech Pharmaceuticals, Inc.
Neurotech is developing sight-saving therapeutics for the treatment of chronic retinal diseases. The Company's lead product candidate, NT-501, is currently in late-stage clinical development for advanced dry age-related macular degeneration (dry AMD) and retinitis pigmentosa (RP). The Company's portfolio of product candidates also includes treatments for wet AMD. All of Neurotech's development programs are based on the Company's proprietary Encapsulated Cell Technology (ECT). ECT uniquely enables the controlled, continuous delivery of biologics directly to the back of the eye, thereby overcoming a major obstacle in the treatment of retinal disease. To learn more, please visit our web site at www.neurotechusa.com.
Virtual Clinical Trials
Global Clinical Development Collaboration Solutions
www.trialinteractive.com
Validate Company's ECT Technology and Support Initiation of Pivotal Studies
LINCOLN, R.I.--(BUSINESS WIRE)--Mar 26, 2009 - Neurotech Pharmaceuticals, Inc., today announced that the Company's lead product candidate, NT-501, substantially slowed the loss of vision in a Phase 2 clinical trial in subjects with dry age-related macular degeneration (AMD) involving geographic atrophy (GA). GA is a condition that destroys sharp central vision, often resulting in serious vision loss to one or both eyes. There are currently no approved treatments for dry AMD. In the study, the high dose of NT-501 stabilized best corrected visual acuity (BCVA) at 12-months, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group.
NT-501 is an intraocular implant that consists of human cells that have been genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is delivered directly to the back of the eye in a controlled, continuous basis by means of the Company's proprietary Encapsulated Cell Technology (ECT) platform, thereby bypassing the blood-retinal barrier and overcoming a major obstacle in the treatment of retinal disease.
The Phase 2 study is a multi-centered, randomized, double-masked, sham-controlled study of 51 subjects with GA. Patients received either a high or low dose NT-501 implant or a sham treatment in one eye only and were assessed for changes in BCVA. BCVA was measured by an Electronic Visual Acuity Tester (EVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Patients were also evaluated for an increase in BCVA. However, no increase was observed, likely due to existing photoreceptor damage. There were no NT-501 associated serious adverse events reported and both NT-501 and the surgical procedure were well-tolerated.
“The favorable functional visual acuity results for patients at this advanced stage of dry AMD are particularly promising due to the significant prevalence of the condition, its serious impact on quality of life and the current unmet medical need for effective therapy," stated Dr. George A. Williams, a study investigator and Professor and Chair of the Department of Ophthalmology at William Beaumont Hospital and the Oakland University William Beaumont School of Medicine in Royal Oak, MI.
The strong trend in visual acuity stabilization at 12 months was preceded by a dose-dependent, statistically significant (p<0.001 and p=0.013 for high and low dose, respectively) increase in retinal thickness as measured by optical coherence tomography (OCT) that was observed as early as 4 months post-implantation. The observed structural change is consistent with preclinical studies of NT-501 in which CNTF was shown to increase the thickness of the retina and the outer nuclear layer of photoreceptors responsible for vision. This increase in retinal thickness may be responsible for photoreceptor rescue and protection as observed in numerous animal models of retinal degeneration.
“Based on the increase in retinal thickness observed in this study it appears that CNTF may be exhibiting a biological effect on retinal photoreceptors as has been observed previously in animal studies,” said Dr. Paul Sieving, Director of the National Eye Institute and Principal Investigator of Neurotech's Phase 1 study of NT-501 in retinitis pigmentosa.
“We believe the anatomical changes observed in patients treated with NT-501 have led to the emergence of a clinically meaningful visual acuity benefit for patients with geographic atrophy,” commented Ted Danse, President and Chief Executive Officer of Neurotech. “NT-501 may provide a much needed treatment option for these patients and we intend to discuss these data and a pivotal trial design with the FDA.”
“We are very pleased that the outcome of this trial has shown such promise for patients with dry AMD involving geographic atrophy and are proud of our long-term support for this unique, breakthrough technology,” stated Stephen Rose, PhD, Chief Research Officer, Foundation Fighting Blindness.
Five devices from this trial have been explanted 12 months following implantation and all have been found to have uniformly healthy, viable cells that continue to produce therapeutic levels of CNTF. This is consistent with data from multiple trials of NT-501 in which, to date, 23 devices have been explanted between 12 and 18 months following implantation and all devices have contained healthy, viable CNTF-producing cells.
“We also believe the positive results of this study and long-term cell viability validate our ECT platform and support a breakthrough opportunity to advance long-term, well-tolerated treatments for patients facing chronic sight-stealing retinal diseases. As such, we are developing our second product utilizing the ECT platform to address a well-validated target, anti-VEGF therapy for wet AMD, that has the potential to provide a one-time administration for a 12 to 18 month period versus the current wet AMD treatment regimen that requires monthly injections with routine patient monitoring,” concluded Danse.
Data from the Phase 2 dry AMD/GA trial will be presented at the Retinal Physician Symposium on March 27, 2009 in the Bahamas, at IBC's 5th International Ocular Angiogenesis & Retinal Degeneration conference on March 31, 2009 in Las Vegas, at the Advanced Vitreoretinal Techniques and Technologies meeting on April 24, 2009 in Las Vegas and at the Association for Research in Vision and Ophthalmology (ARVO) meeting on May 6, 2009 in Ft. Lauderdale.
About Dry AMD/Geographic Atrophy
Age-related macular degeneration (AMD) is a chronic progressive disease of the macula that results in the loss of central vision. It is the leading cause of blindness in elderly people in the developed world. There are two forms of AMD•dry and wet. Dry AMD is the most common form of AMD representing approximately 90% of all AMD cases. In its advanced stages dry AMD can lead to the degeneration of photoreceptors and retinal pigment epithelial cells, a chronic condition called geographic atrophy (GA). There are currently no approved GA therapies for the nearly 1 million individuals affected in the United States.
About NT-501
Neurotech's lead product, NT-501, consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. NT-501 is designed to continually deliver a therapeutic dose of CNTF into the back of the eye.
About Encapsulated Cell Technology
Neurotech's core technology platform is Encapsulated Cell Technology (ECT), a unique technology that allows for the long-term, sustained delivery of therapeutic factors to the back of the eye. ECT implants consist of cells that have been genetically modified to produce a specific therapeutic protein and are encapsulated in a semi-permeable hollow fiber membrane. The diffusive characteristics of the hollow fiber membrane are designed to promote long-term cell survival by allowing the influx of oxygen and nutrients while simultaneously preventing direct contact of the encapsulated cells with the cellular and molecular elements of the immune system. The cells continuously produce the therapeutic protein which diffuses out of the implant at the target site. ECT thereby enables the controlled, continuous delivery of therapeutic factors directly to the retina, bypassing the blood-retina barrier.
About Neurotech Pharmaceuticals, Inc.
Neurotech is developing sight-saving therapeutics for the treatment of chronic retinal diseases. The Company's lead product candidate, NT-501, is currently in late-stage clinical development for advanced dry age-related macular degeneration (dry AMD) and retinitis pigmentosa (RP). The Company's portfolio of product candidates also includes treatments for wet AMD. All of Neurotech's development programs are based on the Company's proprietary Encapsulated Cell Technology (ECT). ECT uniquely enables the controlled, continuous delivery of biologics directly to the back of the eye, thereby overcoming a major obstacle in the treatment of retinal disease. To learn more, please visit our web site at www.neurotechusa.com.
Saturday, March 21, 2009
Macular degeneration may have same biomarker as kidney function
Macular degeneration may have same biomarker as kidney function
Publish date: Mar 5, 2009
Source:Optamology Times
Madison, WI—Cystatin C, a biomarker of kidney function, also may be associated with the incidence of age-related macular degeneration (AMD), said researchers.
Adjusted analyses found that serum levels of the protein were associated with the incidence of both early and exudative AMD, according to Ronald Klein, MD, MPH, and colleagues.
There was an association between chronic kidney disease and macular degeneration, but the association between cystatin C and the degenerative eye disease was intensified in patients without chronic kidney disease.
"This suggests that this relationship might not be due to kidney-related processes," the researchers said.
Studies on the relationship of kidney disease and AMD have been few and inconsistent, so researchers conducted a prospective cohort study of 4,926 patients aged 43 to 86 years, in Beaver Dam, WI.
Publish date: Mar 5, 2009
Source:Optamology Times
Madison, WI—Cystatin C, a biomarker of kidney function, also may be associated with the incidence of age-related macular degeneration (AMD), said researchers.
Adjusted analyses found that serum levels of the protein were associated with the incidence of both early and exudative AMD, according to Ronald Klein, MD, MPH, and colleagues.
There was an association between chronic kidney disease and macular degeneration, but the association between cystatin C and the degenerative eye disease was intensified in patients without chronic kidney disease.
"This suggests that this relationship might not be due to kidney-related processes," the researchers said.
Studies on the relationship of kidney disease and AMD have been few and inconsistent, so researchers conducted a prospective cohort study of 4,926 patients aged 43 to 86 years, in Beaver Dam, WI.
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