Laser Favored Over TA in DME Study
Better Vision, Fewer Side Effects Cited.
BY JERRY HELZNER, SENIOR EDITOR
■ New study data favors focal/grid photocoagulation over preservative-free intravitreal triamcinolone acetonide (TA) as a treatment for diabetic macular edema (DME).
As reported recently in the online edition of the journal Ophthalmology, researchers led by Michael S. Ip, MD, of the Jaeb Center for Health Research in Tampa, FL, randomized 330 patients with DME to focal/grid photocoagulation, while 256 received 1 mg intravitreal TA, and 254 were injected with 4 mg intravitreal TA. Persistent or new edema was retreated at 4-month intervals. Visual acuity (VA), the primary endpoint measure, was evaluated at 2 years.
The researchers reported that VA was initially better in the 4-mg TA group compared to either the laser group or the 1-mg TA group, but no significant differences remained after 1 year of treatment. From the 16-month visit through 2 years, mean VA was significantly better in the laser group compared to the TA groups.
The investigators also reported that IOP increased from baseline by 10 mm Hg or more in 4% of the focal/grid photocoagulation group, and 16% and 33% of eyes in the 1-mg and 4-mg dose groups of preservative-free intravitreal TA, respectively. Cataract surgery was least common in the focal/grid photocoagulation group, the researchers note.
"Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for most patients with diabetic macular edema who have characteristics similar to the cohort in this clinical trial," say the authors. "The results of this study also support that focal/grid photocoagulation currently should be the benchmark against which other treatments are compared in clinical trials of diabetic macular edema."
In light of the results reported in this study, Merck is reevaluating the design of its phase 2b clinical trial for the I-vation sustained-delivery system for TA. Pending this review, Merck is suspending enrollment of new patients in the phase 2b clinical trial. The I-vation system was developed by SurModics.
|■ Alcon ends 2 AMD studies. Alcon, Inc. said it has terminated the development program designed to evaluate the benefit of anecortave acetate treatment on reducing the risk of the dry form of AMD progressing to the wet form of the disease.|
Anecortave acetate (Retaane) was once considered a highly promising treatment for wet AMD after highly encouraging phase 2 trial results. However, those results were not replicated in a pivotal phase 3 trial that ended in 2005. In 2006, Alcon initiated 2 phase 3 studies to determine if anecortave acetate could reduce the risk of dry AMD progressing to the wet form of the disease. It was these clinical trials that have now been ended.
The decision to terminate followed a planned interim analysis of the studies that was performed after 2,546 patients had completed the 24-month timepoint. In this analysis, anecortave acetate showed no statistically significant benefit. In addition to terminating the 2 studies, the company also ended 2 smaller studies with an identical design that were being conducted in Asia.
The company continues to study anecortave acetate administered as an anterior juxtascleral depot to reduce IOP in patients with open-angle glaucoma.
■ Iridex receives clearance on new lasers. Iridex Corp. has received FDA 510(k) clearance to market a new family of lasers that deliver laser energy in either its proprietary Continuous Wave (CW), MicroPulse, or LongPulse modes. The first product in this range will be the IQ 577 laser, which will deliver 577 nm yellow light from a solid-state laser in either CW or MicroPulse mode.
The IQ 577 laser, which is primarily indicated for a variety of retinal photocoagulation procedures, will be introduced this fall, says Iridex.
■ Visudyne sales increase. QLT Inc., developer of Visudyne photodynamic therapy for wet macular degeneration, reported that Visudyne sales for the second quarter increased 11.5% over the first quarter of 2008. Sales in the United States were $10.1 million in the second quarter.
■ Medidur implant shows efficacy. Alimera Sciences reported positive interim 3-month safety and efficacy results from the first human pharmacokinetic (PK) study of Medidur FA, an implanted sustained-release drug for the treatment of diabetic macular edema (DME). Alimera will market the drug under the trade name Iluvien if it is approved by the FDA.
A total of 37 subjects were enrolled in this trial, 20 patients on the low dose (approximately 0.23g per day) of Iluvien, and 17 patients on the high dose (approximately 0.45g per day). The 3-month interim readout from the study indicated 20% of the low-dose patients and 18% of the high-dose patients showed an improvement in BCVA of 15 letters or greater from baseline. In addition, both the low dose and the high dose of Iluvien resulted in a significant reduction in retinal thickness as compared to the baseline.
■ Chew and Ferris receive ARI grants. Emily Y. Chew, MD, and Frederick L. Ferris, MD, who were jointly instrumental in designing, developing, and executing the Age-Related Eye Disease Study, have received unrestricted $100,000 grants from the Alcon Research Institute to continue their research. Dr. Chew is a graduate of the University of Toronto and serves as deputy director, Division of Epidemiology and Clinical Research at the National Eye Institute/National Institute of Health. Dr. Ferris is a graduate of the Johns Hopkins Medical School and currently is the director of Epidemiology and Clinical Research at the National Eye Institute/National Institute of Health.
■ Lucentis sales rise. Genentech reported that sales of its wet AMD treatment Lucentis increased to $216 million in the 3 months ended June 30 vs $209 million in the same period a year ago and $198 million for the first 3 months of 2008.
■ Roche wants all of Genentech. Swiss pharmaceutical maker Roche recently offered $43.7 billion, equivalent to $89 a share, for the remaining shares of its US biotech partner Genentech Inc. Currently, Roche owns approximately 55.9% of the outstanding shares of Genentech. However, Genentech shares have traded well above the $89 figure since the offer was made, which will probably cause Roche to sweeten its bid. Genentech called the $89 offer unacceptable and said it significantly undervalued the company.
Genentech is the developer of Lucentis, the leading treatment for wet AMD.
■ Pfizer funds stem-cell startup. Pfizer is providing early-stage funding for EyeCyte Inc, a stem/progenitor cell-based ophthalmology research and development company. The investment will be primarily used to drive EyeCyte's development of stem-cell treatments for vascular or degenerative eye diseases, with the first target being diabetic retinopathy. Building on research into the causes of, and potential treatments for, retinal disease by Martin Friedlander, MD, PhD, and his laboratory at The Scripps Research Institute in La Jolla, CA, EyeCyte plans to use the properties of blood and bone marrow-derived progenitor cells of patients in its research.
Under the terms of the deal, Pfizer has invested $3 million in Series A Preferred shares of EyeCyte. Pfizer will be the sole pharmaceutical partner and will have an advisory role, including representation on EyeCyte's board of directors. Pfizer will also have right of first refusal for a buyout of EyeCyte or its technologies. RP
Stem Cell Treatment Shows Promise
Small Study Offers Encouraging Results
■ A 10-patient clinical study undertaken by a Kentucky researcher is offering encouragement to those who believe that the best hope for treating vision-robbing retinal disease lies in the area of stem cell transplants.
Results from the study were recently reported in the American Journal of Ophthalmology.
Norman D. Radtke, MD, of the University of Louisville and colleagues implanted fetal retinal stem cells along with their attached retinal pigment epithelium in 10 patients with vision loss resulting from degenerative retinal disease. Six of the patients were afflicted with retinitis pigmentosa (RP) and 4 with dry AMD.
The hope was that the new cells would grow to replace the damaged photoreceptor cells while connecting to the patient's remaining retina.
The research data showed visual improvements in 7 of the 10 patients, including all 4 of the patients with AMD. Though all of the patients remained legally blind following the treatment, researchers reported that vision gains were significant and measurable. "This clinical evidence shows the promise of our method to alter progressive vision loss due to incurable degenerative diseases of the retina," said Dr. Radtke.
In 1 patient with RP, visual improvement was demonstrated up to 6 years after surgery, though vision in the untreated eye continued to deteriorate. That patient showed a 27% increase in light sensitivity in the treated eye.
There was no incidence of rejection of the transplants by the patients' immune systems despite the lack of a perfect immunological match between the transplant donors and recipients. Two patients also had improved vision in the untreated eyes. The reason for this unexpected finding is unknown and is likely to be the subject of further research.
The design of the transplant procedure was based on animal studies showing that transplantation of retinal cells can lead to the development of new retinal tissues. Earlier phase 1 studies had established the fact that the procedure could be performed safely on humans. This latest trial provides the first evidence of improved vision through retinal stem cell transplantation.
Additional studies will be required to determine the potential for retinal transplantation for degenerative retinal disease.
"Retinal implants that combine retina and retinal pigment epithelium demonstrated an apparent ability to integrate with host retinas and to re-establish the visual pathways interrupted by disease," concluded Dr. Radtke. "What we have learned will help us to refine this method and obtain further evidence that retinal implants may be a viable therapy for retinal degenerative disease."
SiRNA Drug in Study for DME
Quark/Pfizer Also See Wet AMD Potential.
■ Quark Pharmaceuticals, a development-stage pharmaceutical company focusing on RNA interference (RNAi)-based therapeutics, along with its partner Pfizer, recently initiated patient dosing in a phase 2 trial evaluating PF-4523655 in patients with diabetic macular edema (DME).
PF-4523655 is a novel small interfering RNA (siRNA) drug candidate co-developed by Quark and Pfizer. The start of the trial triggers a milestone payment to Quark from Pfizer.
There are now 3 clinical trials currently under way using investigational siRNA drugs for the treatment of retinal disease. In addition to the Quark/Pfizer study for DME, Merck and OPKO Health are in phase 3 trials with drugs for the treatment of the wet form of AMD.
The Quark/Pfizer phase 2 prospective, randomized, dose-ranging study is intended to evaluate the safety and efficacy of PF-4523655 vs laser therapy in 160 DME patients at multiple centers worldwide. PF-4523655 was designed to inhibit Quark's proprietary target RTP801, a gene involved in abnormal blood vessel development and leakage in the eye. Under the licensing agreement, Pfizer has exclusive development rights to siRNA-mediated therapies that inhibit RTP801 for ophthalmic and non-ophthalmic indications, while Quark is eligible for development and sales based milestone payments.
Elena Feinstein, Quark's chief scientific officer, said that "by targeting the RTP801 gene, PF-4523655 is differentiated from other therapeutics for the same ophthalmic indications. While many competitors target VEGF and its receptors, PF-4523655 inhibits abnormal blood vessel growth and leakage independently of the VEGF pathway, reduces inflammation, and suppresses apoptosis. Therefore, PF-4523655 is a siRNA therapeutic candidate with the potential to be efficacious when used as a monotherapy and in combination with existing VEGF-based therapies."
Quark said that results from a phase 1/2 trial completed by Quark on Pfizer's behalf showed that PF-4523655 was safe and well tolerated in patients with wet-AMD who failed to respond to currently approved therapies. Based on data from this trial, Pfizer decided to pursue a phase 2 trial in DME. In addition, Quark and Pfizer are considering an additional phase 2 study of PF-4523655 in patients with wet AMD.