By Dr. Randall Wong
Many of us just returned from the largest ophthalmic “trade show” in the world. The American Academy of Ophthalmology convened in Chicago last week. This meeting was combined with the Middle East Africa Council of Ophthalmology (MEACO). Perhaps 40 K attended the meeting.
I also attended the 2 day retinal subspecialty meeting which preceded the larger AAO meeting. Thus, I had 5 days to expand my knowledge.
Most of the congress was focused on technology, especially electronic medical records. Few discoveries were revealed. This may be for two reasons: there is nothing really new going on right now, and/or, the Internet allows such rapid sharing of information, that it is impossible to “wow” anyone at this meeting. Probably both are true.
With regard to retinal disease, my particular specialty, there is little new, but lots to be excited about.
Avastin and Lucentis continue to be the mainstays of treatment for wet macular degeneration. There is evidence that the two drugs are similar in clinical efficacy…a notion I support. It is likely that these types of drugs will be delivered with a sustained release system, thus, obviating the need for repeated intraocular injections.
Ozurdex is now indicated for the treatment of uveitis. It was originally FDA approved for the treatment of RVO only. By itself, not earth-shattering, but does make sense clinically. Sustained release steroids for chronic intraocular inflammation. Sounds much better.
The highlight of the meeting is the potential for Iluvien to be FDA approved soon. Iluvien is similar to Ozurdex in that both are injectable intraocular sustained release systems. Iluvien will be a sustained release system that delivers intraocular steroids for the treatment of diabetic macular edema. While this is a particularly promising development for patients with diabetic retinopathy, this has larger implications for eye treatment overall.
What Does This Mean? Illuvien is likely to be the second FDA approved intraocular drug delivery system. This will be a significant endorsement of drug delivery to the eye. We are entering a new era of pharmaceutical therapeutics; sustained release inside the eye. For now, we are focused on retinal disease. But soon, very soon, devices will emerge promising better therapeutics for almost any eye condition.
Just think, glaucoma may be treated by such a device.
Saturday, October 30, 2010
Saturday, October 23, 2010
Novartis therapy Lucentis recommended for approval in EU to treat Diabetic Macular Edema
By Thomas Reuters
- CHMP positive opinion supports Lucentis approval in EU for treatment in patients with visual impairment due to diabetic macular edema (DME)
- Pivotal data shows Lucentis provided rapid, superior and sustained vision gains compared to the current standard of care
- Diabetes-associated eye diseases such as DME are a leading cause of blindness in most developed countries in the working-age population
Basel, October 22, 2010 - Novartis has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for Lucentis(R) (ranibizumab) for the treatment of patients with visual impairment due to diabetic macular edema (DME), a leading cause of blindness in the working-age population in most developed countries.
"Lucentis was designed specifically for use in the eye, and its efficacy and safety have now been demonstrated in patients suffering loss of vision due to diabetic macular edema through a robust program of clinical trials," said David Epstein, Division Head of Novartis Pharmaceuticals.
The submission was supported by data from two Novartis-funded clinical trials, RESTORE and RESOLVE, which showed that Lucentis was superior in providing rapid and sustained visual acuity gain versus sham (dummy therapy) or laser therapy, the current standard of care. The RESTORE study showed patients treated with Lucentis alone or with Lucentis plus laser therapy achieved an average 5.9 letters and 5.5 letters gain in visual acuity at 12 months, respectively, compared to laser-treated patients as measured on a standard ETDRS eye chart.
The RESOLVE study showed that Lucentis-treated patients achieved an average 11.7 letters gain in visual acuity at 12 months compared to sham-treated patients, some of whom received laser treatment.
The pivotal data from RESTORE and RESOLVE are further supported by results of an independent US study conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net), showing that at one year nearly 50% of patients' eyes treated with Lucentis and laser therapy improved their visual acuity by 10 letters or more, compared to 28% with laser alone. In addition, the study demonstrated superior gains in visual acuity among Lucentis-treated patients up to two years.
Lucentis was generally well tolerated in clinical studies, either when given as monotherapy or when combined with laser treatment. Its safety profile was consistent with that previously reported in large controlled clinical trials, and in rigorous monitoring since Lucentis was first approved for wet age-related macular degeneration (AMD). Lucentis is currently licensed in more than 85 countries for the treatment of wet AMD.
Diabetic macular edema (DME) is a consequence of diabetic retinopathy - the most common diabetic eye complication, characterized by changes in the blood vessels of the retina - to the light-sensitive layer at the back of the eye. In patients with DME, leakage from these abnormal blood vessels occurs in the central portion of the retina, called the macula. Because this part of the eye is responsible for sharp central vision, DME can lead to significant visual impairment. Visual impairment due to DME affects approximately 1-3% of patients with diabetes, and DME is a leading cause of blindness in the working-age population in most developed countries.
Lucentis offers an entirely new pharmacological approach to treatment compared to the current standard of care for DME that involves the use of laser burns to stop the capillary leakage and to reduce swelling. Lucentis is an antibody fragment that is injected into the eye and acts by neutralizing vascular endothelial growth factor (VEGF), a protein that is known to increase vascular permeability, resulting in capillary leakage and macular edema in patients with diabetes.
Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States where Lucentis is also approved for the treatment of macular edema following retinal vein occlusion (RVO). In addition, Genentech is conducting two Phase III studies, RISE and RIDE, in patients with diabetic macular edema. The results are expected in 2011. Novartis has exclusive rights in the rest of the world and plans to file in the European Union for approval of Lucentis for the treatment of visual impairment due to macular edema following RVO.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "recommended," "plans," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Lucentis or regarding potential future revenues from Lucentis. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Lucentis to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Lucentis will be submitted or approved for any additional indications or labeling in any market. Nor can there be any guarantee that Lucentis will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Lucentis could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
- CHMP positive opinion supports Lucentis approval in EU for treatment in patients with visual impairment due to diabetic macular edema (DME)
- Pivotal data shows Lucentis provided rapid, superior and sustained vision gains compared to the current standard of care
- Diabetes-associated eye diseases such as DME are a leading cause of blindness in most developed countries in the working-age population
Basel, October 22, 2010 - Novartis has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for Lucentis(R) (ranibizumab) for the treatment of patients with visual impairment due to diabetic macular edema (DME), a leading cause of blindness in the working-age population in most developed countries.
"Lucentis was designed specifically for use in the eye, and its efficacy and safety have now been demonstrated in patients suffering loss of vision due to diabetic macular edema through a robust program of clinical trials," said David Epstein, Division Head of Novartis Pharmaceuticals.
The submission was supported by data from two Novartis-funded clinical trials, RESTORE and RESOLVE, which showed that Lucentis was superior in providing rapid and sustained visual acuity gain versus sham (dummy therapy) or laser therapy, the current standard of care. The RESTORE study showed patients treated with Lucentis alone or with Lucentis plus laser therapy achieved an average 5.9 letters and 5.5 letters gain in visual acuity at 12 months, respectively, compared to laser-treated patients as measured on a standard ETDRS eye chart.
The RESOLVE study showed that Lucentis-treated patients achieved an average 11.7 letters gain in visual acuity at 12 months compared to sham-treated patients, some of whom received laser treatment.
The pivotal data from RESTORE and RESOLVE are further supported by results of an independent US study conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net), showing that at one year nearly 50% of patients' eyes treated with Lucentis and laser therapy improved their visual acuity by 10 letters or more, compared to 28% with laser alone. In addition, the study demonstrated superior gains in visual acuity among Lucentis-treated patients up to two years.
Lucentis was generally well tolerated in clinical studies, either when given as monotherapy or when combined with laser treatment. Its safety profile was consistent with that previously reported in large controlled clinical trials, and in rigorous monitoring since Lucentis was first approved for wet age-related macular degeneration (AMD). Lucentis is currently licensed in more than 85 countries for the treatment of wet AMD.
Diabetic macular edema (DME) is a consequence of diabetic retinopathy - the most common diabetic eye complication, characterized by changes in the blood vessels of the retina - to the light-sensitive layer at the back of the eye. In patients with DME, leakage from these abnormal blood vessels occurs in the central portion of the retina, called the macula. Because this part of the eye is responsible for sharp central vision, DME can lead to significant visual impairment. Visual impairment due to DME affects approximately 1-3% of patients with diabetes, and DME is a leading cause of blindness in the working-age population in most developed countries.
Lucentis offers an entirely new pharmacological approach to treatment compared to the current standard of care for DME that involves the use of laser burns to stop the capillary leakage and to reduce swelling. Lucentis is an antibody fragment that is injected into the eye and acts by neutralizing vascular endothelial growth factor (VEGF), a protein that is known to increase vascular permeability, resulting in capillary leakage and macular edema in patients with diabetes.
Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States where Lucentis is also approved for the treatment of macular edema following retinal vein occlusion (RVO). In addition, Genentech is conducting two Phase III studies, RISE and RIDE, in patients with diabetic macular edema. The results are expected in 2011. Novartis has exclusive rights in the rest of the world and plans to file in the European Union for approval of Lucentis for the treatment of visual impairment due to macular edema following RVO.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "recommended," "plans," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Lucentis or regarding potential future revenues from Lucentis. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Lucentis to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Lucentis will be submitted or approved for any additional indications or labeling in any market. Nor can there be any guarantee that Lucentis will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Lucentis could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Sunday, October 17, 2010
Complement inhibition may be the future of dry AMD therapy
CHICAGO — Ongoing clinical trials exploring the use of complement inhibitors for treating nonexudative age-related macular degeneration offer promise for a disease state that has long been considered difficult to treat.
A number of recent studies have implicated the complement immune system in AMD. However, nonexudative AMD remains a "uniquely human disease," and, therefore, no animal model exists in which to prove potential therapeutic strategies, Philip J. Rosenfeld, MD, PhD, said here are Retina Subspecialty day preceding the joint meeting of the American Academy of Ophthalmology and the Middle East Africa Council of Ophthalmology.
As a result, Dr. Rosenfeld said, human trials will prove important in determining whether complement inhibition is of any real clinical benefit.
Several such trials are already underway. Alcon is currently investigating its POT-4 (AL-78898A) anti-C3 cyclic peptide in human trials. There is some evidence that POT-4 may also affect VEGF expression in the retina, Dr. Rosenfeld said.
Separately, Genetech/Roche has an anti-factor D (FCFD4514S) that inhibits the C3 and C5 alternative pathway convertases. Phase 1 studies have been successfully completed with that agent, Dr. Rosenfeld said.
Two separate C5 inhibitors are being studied: Eculizumab/Sollris (Alexion) and ARC1905, an anti-C5 aptamer (Ophthotech).
"One of the advantages is that while you block the downstream activated species, you preserve the more proximal species that are important for the clearance of bacteria, particularly the encapsulated organisms," Dr. Rosenfeld said.
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A number of recent studies have implicated the complement immune system in AMD. However, nonexudative AMD remains a "uniquely human disease," and, therefore, no animal model exists in which to prove potential therapeutic strategies, Philip J. Rosenfeld, MD, PhD, said here are Retina Subspecialty day preceding the joint meeting of the American Academy of Ophthalmology and the Middle East Africa Council of Ophthalmology.
As a result, Dr. Rosenfeld said, human trials will prove important in determining whether complement inhibition is of any real clinical benefit.
Several such trials are already underway. Alcon is currently investigating its POT-4 (AL-78898A) anti-C3 cyclic peptide in human trials. There is some evidence that POT-4 may also affect VEGF expression in the retina, Dr. Rosenfeld said.
Separately, Genetech/Roche has an anti-factor D (FCFD4514S) that inhibits the C3 and C5 alternative pathway convertases. Phase 1 studies have been successfully completed with that agent, Dr. Rosenfeld said.
Two separate C5 inhibitors are being studied: Eculizumab/Sollris (Alexion) and ARC1905, an anti-C5 aptamer (Ophthotech).
"One of the advantages is that while you block the downstream activated species, you preserve the more proximal species that are important for the clearance of bacteria, particularly the encapsulated organisms," Dr. Rosenfeld said.
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Sunday, October 10, 2010
Angiogenesis Discovery Points to Novel Therapy for Multiple Diseases
Tatiana Byzova, PhD, a faculty member in Lerner Research Institute's Department of Molecular Cardiology and Director of the Center for Angiogenesis Research, and colleagues have discovered a fundamental biological pathway in angiogenesis (formation of blood vessels), published online October 3, 2010 in Nature (DOI: 10.1038/nature09421). The significance of this discovery is summarized by Dr. Byzova, in that "it affects many biological processes - from wound healing to aging."
Some pathologies included in that spectrum are age-related macular degeneration, atherosclerosis, and rheumatoid arthritis, while their published data indicate a particularly notable role in cancer. The results of this advanced understanding point to an exciting new approach for novel therapies.
In 1989, a protein called vascular endothelial growth factor (VEGF) was identified as a trigger of angiogenesis. This discovery led Genentech to develop the first effective treatment for macular degeneration; related work contributed to the development of a drug to block VEGF function in cancer, essentially starving the tumor of the nutrients the blood would otherwise bring.
However, although many tumors respond to anti-VEGF treatment, most develop resistance to the therapy and continue to survive over time. One possible explanation is that VEGF is not the only trigger leading to angiogenesis. This is precisely what Dr. Byzova's team has found.
Dr. Byzova's research has identified a class of oxidized lipids that are abundantly present in highly vasculated tumors. Further interrogation parsed out the process through which these products induce new blood vessel formation. It appears that cells use a family of receptors previously known to recognize foreign products such as bacteria to sense and respond to the danger of oxidation. The results point to a novel therapy that may well be an alternate way to starve the tumors that have managed to survive despite VEGF inhibition. Through uncovering a potential way to get around tumor resistance to VEGF, Dr. Byzova's group has opened up new doors for developing treatments for cancer. The fundamental discovery also provides substantial insight for novel treatments for other diseases that involve inflammation, oxidative stress, and angiogenesis.
Overall, this foundational discovery of a novel mechanism of angiogenesis comes just one year after Dr. Byzova headed a study that pioneered the identification of a new genetic-based human disease, published in Nature Medicine.
Some pathologies included in that spectrum are age-related macular degeneration, atherosclerosis, and rheumatoid arthritis, while their published data indicate a particularly notable role in cancer. The results of this advanced understanding point to an exciting new approach for novel therapies.
In 1989, a protein called vascular endothelial growth factor (VEGF) was identified as a trigger of angiogenesis. This discovery led Genentech to develop the first effective treatment for macular degeneration; related work contributed to the development of a drug to block VEGF function in cancer, essentially starving the tumor of the nutrients the blood would otherwise bring.
However, although many tumors respond to anti-VEGF treatment, most develop resistance to the therapy and continue to survive over time. One possible explanation is that VEGF is not the only trigger leading to angiogenesis. This is precisely what Dr. Byzova's team has found.
Dr. Byzova's research has identified a class of oxidized lipids that are abundantly present in highly vasculated tumors. Further interrogation parsed out the process through which these products induce new blood vessel formation. It appears that cells use a family of receptors previously known to recognize foreign products such as bacteria to sense and respond to the danger of oxidation. The results point to a novel therapy that may well be an alternate way to starve the tumors that have managed to survive despite VEGF inhibition. Through uncovering a potential way to get around tumor resistance to VEGF, Dr. Byzova's group has opened up new doors for developing treatments for cancer. The fundamental discovery also provides substantial insight for novel treatments for other diseases that involve inflammation, oxidative stress, and angiogenesis.
Overall, this foundational discovery of a novel mechanism of angiogenesis comes just one year after Dr. Byzova headed a study that pioneered the identification of a new genetic-based human disease, published in Nature Medicine.
Monday, October 4, 2010
Retinal Degeneration Can be Prevented with Nanotechnology Gene Therapy
Friday, 01 October 2010
Researchers from Tufts University published results from a study showing vision-saving gene therapy to the eyes can be delivered via nanotechnology. A protein called Glial Cell Line-Derived Neurtrophic Factor (GDNF) can protect the eyes from diseases of the retina, such as and retinitis pigmentosa.
The previous method for delivering genetic material with a virus had several problems and side effects. Although the study is in its infancy, and the results are temporary, mice injected with the GDNF carrying nanoparticle had a 3.9 to 7.7-fold reduction in damage to the retina. Seven days after treatment, the GDNF-nanoparticle treated mice had up to 39% better eyesight than mice in the control group.
Two weeks after the treatment, GDNF-nanoparticle-injected mice had nuclear layers of the retina that were almost 24 to over 39 percent thicker than control mice. However, after 14 days, these advantages seem to have vanished. According to Dr. Brett Katzen, "The idea of using gene therapy to help cure - or at least improve - the eyesight of patients with macular degeneration should be exciting to eye doctors everywhere. This is a great first step." The research shows an incredible potential for nanotechnology to develop an effective carrier for delivering gene therapy.
This therapy can then lead to a new generation of treatments for retinal diseases. Age-related macular degeneration is the leading cause of blindness in Americans over the age of 65.
Researchers from Tufts University published results from a study showing vision-saving gene therapy to the eyes can be delivered via nanotechnology. A protein called Glial Cell Line-Derived Neurtrophic Factor (GDNF) can protect the eyes from diseases of the retina, such as and retinitis pigmentosa.
The previous method for delivering genetic material with a virus had several problems and side effects. Although the study is in its infancy, and the results are temporary, mice injected with the GDNF carrying nanoparticle had a 3.9 to 7.7-fold reduction in damage to the retina. Seven days after treatment, the GDNF-nanoparticle treated mice had up to 39% better eyesight than mice in the control group.
Two weeks after the treatment, GDNF-nanoparticle-injected mice had nuclear layers of the retina that were almost 24 to over 39 percent thicker than control mice. However, after 14 days, these advantages seem to have vanished. According to Dr. Brett Katzen, "The idea of using gene therapy to help cure - or at least improve - the eyesight of patients with macular degeneration should be exciting to eye doctors everywhere. This is a great first step." The research shows an incredible potential for nanotechnology to develop an effective carrier for delivering gene therapy.
This therapy can then lead to a new generation of treatments for retinal diseases. Age-related macular degeneration is the leading cause of blindness in Americans over the age of 65.
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