New Brunswick joins Newfoundland and Labrador as only the second Atlantic Canadian province to provide coverage for Lucentis treatments.  With the annoucement, New Brunswick joins Newfoundland and Labrador, Quebec, Ontario, British Columbia, Saskatchewan, the Yukon and Alberta in providing treatments for patients diagnosed with wet macular degeneration.

People diagnosed with wet macular degeneration generally experience a rapid deterioration of their central vision that eventually leads to blindless.  Lucentis has become the treatment standard for wet macular degeneration and has been shown to dramatically improve the vision in the majority of the patients receiving the injections.  In clinical trials, Lucentis was shown to improve the vision of approximately 40 percent of patients to a visual acuity of 20/40 or better.

In March 2008, the Common Drug Review (CDR), Canada’s national drug review panel recommended that Lucentis be covered under provincial drug plans.  Ontario and Quebec were the first provinces to provide coverage of Lucentis for macular degeneration.

Lucentis is designed specifically for use in teh eye and is administered through injections.  Wet macular degeneration is characterized by the formation of abnormal blood vessels and leakages behind the retina that results in the loss of central vision.  Lucentis treatments targets these abnormal blood vessels and prevents further leakages from occurring.

With New Brunswick being the latest Canadian province to provide coverage for Lucentis, one can only hope that the remaining provinces will follow suit.

The dry macular degeneration eye drop MC-1101 delivered through Mystic’s VersiDoser delivery system successfully reached the back of the eye and modulated blood flow in the choroid.  The delivery system allowed patients suffering from dry macular degeneration to self-administer the eye drop to the front of the eye.

VersiDoser regulates the dosage level and frequency of the eye drop in those patients suffering from dry macular degeneration.  The regulation of MC-1101 dosing allows for the delivery of a preservative-free formulation of the drug.  This precise delivery of the eye drop facilitated the absorption of the drug to the back of the eye affected with dry macular degeneration.

According to MacuClear president and CEO Philip G. Ralston Jr., “We are very pleased with the groundbreaking results of this study.  We have confirmed the safety of MC-1101 in humans, a primary endpoint for the study.”  Mystic president Timothy Sullivan said that “An overwhelming majority of trial participants expressed a strong positive preference for using the VeriDoser delivery system over traditional eye drop delivery.”

Further studies in the dry macular degeneration eye drops are expected to continue later in the year.rop

Avastin (bevacizumab) and Lucentis (ranibizumab) were compared in a double-masked, randomized controlled trial.  Lucentis is the preferred macular degeneration treatment and is approved by the FDA.  Avastin is an off-label macular degeneration treatment and was originally approved to treat colo-rectal cancer.

Until this recent study, there was no data supporting which macular degeneration drug was effective.

In this study, the Veterans Affairs Boston Healthcare System funded a study where patients were enrolled by a 2 to 1 randomization to either the Avastin or Lucentis treatment.  Patients were given intravitreal injections of either Avastin or Lucentis every month for the first three months of the trial and evaluated after the third injection to determine if subsequent macular degeneration treatments were required.

It was shown that at six months, there was no difference in those patients treated with Avastin or Lucentis.

This adds fuel to the debate over which of the two drugs should be used to treat macular degeneration.  Genentech refused to conduct any trials of Avastin as a macular degeneration treatment stating that Lucentis is the FDA approved treatment for the eye disease.

However, Avastin costs approximately $40 per treatment while Lucentis costs approximately $2000 per treatment.  With some patients requiring multiple injections to treat their macular degeneartion, the costs associated with Lucentis treatments can be enormous.

Macular degeneration is an eye disease that involves the degeneration of light-sensitive retinal cells in the eye.  Treatments are currently available for only wet macular degeneration, leaving people suffering from dry macular degeneration with little or no treatment options.

Growing retinal cells from skin cells could lead to a new treatment for macular degeneration.

As part of their research, human skin cells were manipulated to act like embryonic stem cells.  Stem cells can then be used to grow into any tissue in the body, including retinal cells.  This research suggests that doctors may be able to repair retinal cells damaged by macular degeneration by growing new cells generated from a patients own skin.

People with macular degeneration and retinitis pigmentosa, eye diseaseas that eventually lead to blindness, may benefit from this possible new treatment.

According to David Gamm, a professor of ophthalmology and visual sciences at the University of Wisconsin, the laboratory process of creating human retinal cells helps researchers understand how eyes develop, so disease (such as macular degeneration) that lead to vision loss may someday be treated or even cured with retinal stem cells.

This research comes after several other researchers have announced successes using stem cells to treat macular degeneration.

 Tachyphylaxis, or the densensitization of the body to the drug being used, results in a loss of effectiveness of the drug over a period of time. When drugs such as Avastin have to be used over a prolongued period of time. It is thought that this desensitization will occur more frequently when drugs are used with a single target in mind. This is the case with using Avastin to treat macular degeneration. Avastin is used to target the growth of abnormal blood vessels associated with the eye disease.

The researchers reviewed a series of 59 patients whose macular degeneration was treated with the drug avastin. The study took place over a 14-month period and identified those patients that had demonstrated a loss of effectiveness of the drug avastin. Patients were treated with the drug and the effectiveness measured using an OCT.

5 patients were identified to have developed a decreased effectiveness to Avastin when it was used to treat their macular degeneration. Increased dosage did not restore the effectiveness of the drug, and it was apparent that these patients had developed some degree of resitance to Avastin.

It was noted that the median time to develop tachyphylaxis was 100 weeks and the medium number of Avastin treatments to develop the reistance was 8 treatments. This leads to great concern because typically macular degeneration patients require prolongued treatments with anti-VEGF drugs such as Avastin and Lucentis. This means an increased drug resistance over a period of time and eye specialists must ensure that injects of drugs such as Avastin are kept to an absolute minimum.

Further research into the development of a a drug resistance to Avastin when used to treat macular degeneration is ongoing. It is hoped that this desensitization can be reduced by combining Avastin with na intravitreal steroid.

Fenretinide is an oral vitamin A binding protein that has been used in patients with advanced dry macular degeneration.  It is believed that the accumulation of retinol or vitamin A toxins can be halted by Fenretinide, thus slowing the formation and accumulation of toxic by-products typically associated with dry macular degeneration.

Patients in the Phase II trial were either treated with a placebo or fenretinide.  Patients treated with 300 mg of oral fenretinide showed slower growth and slower progression of their dry macular degeneration, 22.7 percent versus 41.6 percent in the placebo growth.

Based on the results, Sirion plans to continue its study to its conclusion and will meet with its scientific advisors and FDA to design an an appropriate Phase III trial for fenretinide.

With the results of Fenretinide at slowing the progression of dry macular degeneration, this may offer hopes to those patients diagnosed with the eye disease.  Currently, there are few treatment options for dry macular degeneration.

While at the Willis Eye Institute Alumni Conference, Jason S. Slakter, MD indicated that the drugs Lucentis, Macugen and the off-label drug Avastin have revolutionized the treatment of wet macular degeneration in the last several years.  However, it was noted that these anti-VEGF drugs are not effective for all macular degeneration patients and Dr. Slakter indicated that new treatments for the eye disease were being developed.

Some of the macular degeneration treatments discussed included Sirolimus, a drug that targets mTOR, a protein that plays a role in promoting VEGF.  This agent is in phase 2 clinical trials and shows promise as an effective treatment for this eye disease.

RTP801, a small interfering RNA molecule that supresses VEGF production is in phase 1 trials for intravitrial delivery.

VEGF Trap-Eye being developed by Bayer Healthcare and Regeneron is in phase 3 testing against the popular macular degeneration drug Lucentis.  The VEGF Trap-Eye is a fusion protein that inhibits the VEGF molecule and has been shown to be effective in improving the visual acuity and in reducing choroidal neovascularization in macular degeneration patients.

The advancements in treatments are not limited to wet macular degeneration.  There are emerging treatments as well for dry macular degeneration including an implant that produces and delivers ciliary neurotrophic fact, a neuroprotective agent.  The early data from the phase 2 trial of geographic atrophy has shown favourable results according to Dr. Slakter.

With these many emerging macular degeneration treatments, patients can feel somewhat relieved that there are advancements occurring in treating this eye disease.

This treatment for wet macular degeneration applies a targeted dose of radiation to the leaking blood vessels that affect the central vision of the eye.  In this treatment, two injections of an anti-VEGF drug such as Avastin are delivered as a treatment at the same time as the radiation.

The preliminary data shows that the targeted radiation therapy for macular degeneration is both safe for the patient and the administering physician, as well as may provide a mechanism to restore the patient’s vision.  This expands the current treatment of wet macular degeneration which is generally ongoing injections of anti-VEGF drugs such as Avastin, Lucentis and Macugen.

The patients that received this radiation therapy for macular degeneration were examined after an 18-month follow-up and 25 trial participants showed an average improvement in visual acuity of 10.7 letters;  96 percent of the patients loss 15 letters or fewer, while 76 percent gained some letters.  44 percent gained 15 letters or more, while 8 percent gained 30 letters or more.

The most interesting aspect of the study showed that 68 percent of the participants did not require additional injections of Avastin to treat their wet macular degeneration.  The average number of injections of Avastin to treat the wet macular degeneration was only 2.4 injections by month 18.

With the success of the Phase II trials, Neovista continues to enroll patients in the company’s Phase III trials, which will use the same radiation therapy at the same time as the FDA approved anti-VEGF drug for wet macular dgeneration Lucentis versus Lucentis alone as a treatent for wet macular degeneration.

The study showed that VEGF Trap-Eye was also associated with a reduction in the size of the choroidal neovascular membrane (CNV), the active lesion that is the underlying cause of vision loss in patients with wet AMD. Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 milligrams (mg) for 12 weeks followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001 versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively. Patients in the 2.0 mg monthly cohort also achieved a statistically significant 1.75 mm2 reduction in total lesion size. A reduction in total lesion size was not seen in the cohort initially dosed with 0.5 mg monthly.

“Progression of the active CNV lesion and resulting vision impairment are an inevitable consequence of untreated wet macular degeneration. The reduction in total active CNV lesion size achieved with VEGF Trap-Eye treatment in this Phase 2 clinical study could potentially translate into clinically meaningful outcomes in the larger, controlled Phase 3 studies that are underway,” stated Jason Slakter, M.D., head of the independent reading center for the study and a Clinical Professor of Ophthalmology, New York University School of Medicine, New York.

In this double-masked Phase 2 trial, participants were initially treated with either monthly or quarterly fixed dosing for 12 weeks and then continued to receive treatment for another 40 weeks on a PRN (as needed) dosing schedule. Patients receiving fixed monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 milligrams (mg) for 12 weeks (i.e. 4 fixed doses) followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001 versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively, at the end of one year. The proportion of patients with vision of 20/40 or better (part of the legal minimum medical requirement for an unrestricted driver’s license in the U.S.) increased from 23 percent at baseline to 45 percent at week 52 in patients initially treated with 2.0 mg monthly and from 16 percent at baseline to 47 percent at week 52 in patients initially treated with 0.5 mg monthly. During the week 12 to week 52 PRN dosing period, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6 additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections.

Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 mg for 12 weeks followed by PRN dosing also achieved mean decreases in retinal thickness versus baseline of 143 microns (p<0.0001 versus baseline) and 125 microns (p<0.0001 versus baseline) at week 52, respectively.

While PRN dosing following a fixed quarterly dosing regimen (with dosing at baseline and week 12) also yielded improvements in visual acuity and retinal thickness versus baseline at week 52, the results generally were not as robust as those obtained with initial monthly treatment.

“Anti-VEGF therapy has dramatically changed the treatment paradigm for wet macular degeneration, and improvement in visual acuity is now feasible in most patients. The biggest challenge we have is that with our current drugs, the majority of patients need frequent injections into their eye to maintain their visual acuity gains,” stated David M. Brown, M.D., a study investigator and a retinal specialist at The Methodist Hospital in Houston.”These study results reinforce our interest in further exploring whether continued administration of VEGF Trap-Eye on an as-needed basis after an initial period of fixed dosing can maintain a durability of effect over time in controlled Phase 3 clinical studies.”

VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was one reported case of eye inflammation (culture-negative endophthalmitis/uveitis) in the study eye, which was deemed not to be drug-related. The most common adverse events were those typically associated with intravitreal injections.

About the Phase 3 Program in Wet Macular Degeneration
Regeneron and Bayer HealthCare initiated a Phase 3 global development program for VEGF Trap-Eye in wet macular degeneration in August 2007. In two Phase 3 trials, VIEW 1 and VIEW 2 (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet age related macular degeneration), the companies are evaluating VEGF Trap-Eye dosed 0.5 mg every 4 weeks, 2 mg every 4 weeks, or 2 mg every 8 weeks (following three monthly doses) in direct comparison with ranibizumab (Lucentis®, a registered trademark of Genentech, Inc.) administered 0.5 mg every four weeks according to its U.S. label during the first year of the studies. PRN dosing will be evaluated during the second year of each study. The VIEW 1 study (http://www.regeneron.com/vegftrap_eye.html) is currently enrolling patients in the United States and Canada and the VIEW 2 study (www.view2study.com) is currently enrolling patients in Europe, Asia Pacific, Japan and Latin America. The companies are collaborating on the global development of VEGF Trap-Eye for the treatment of wet macular degeneration, diabetic eye diseases, and other eye diseases and disorders. Bayer HealthCare will market VEGF Trap-Eye outside the United States, where the companies will share equally in profits from any future sales of VEGF Trap-Eye. Regeneron maintains exclusive rights to VEGF Trap-Eye in the United States.

About VEGF Trap-Eye
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body’s tissues and organs. It has also been associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with the related placental growth factor (PlGF). VEGF Trap-Eye is a specific and highly potent blocker of these growth factors. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet macular degeneration.

About Wet Macular Degeneration 
Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (nonexudative) or wet (exudative). In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid. This leakage causes disruption and dysfunction of the retina creating blind spots in central vision, and it can account for blindness in wet macular degeneration patients. Wet macular degeneration is the leading cause of blindness for people over the age of 65 in the U.S. and Europe.

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.  

Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, General Medicine, Specialty Medicine and Women’s Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at www.bayerscheringpharma.de.

Forward-looking statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

With age-related macular degeneration, the eye disease attacks the macula of the eye resulting in the progressive degeneration of this portion of the retina. This results in the loss of central vision, while peripheral vision generally remains normal.

Wet macular degeneration is characterized by choroidal neovascularization (CNV). This is the development of abnormal blood vessels developing beneath the retina. These blood vessels bleed and cause scarring on the macula which results in the loss of central vision. Wet macular degeneration progresses relatively fast and should be treated as soon as diagnosed.

With wet macular degeneration, there are some signs and symptoms of macular degeneration that may appear and progress quickly. THese include:

• visual distortions where straight lines appear wavey or crooked;
• loss of central vision;
• requiring more light to read;
• blurry or blind spot in the field of vision

It is important to have regular eye examinations after the age of 50 or if you are subject to many of the risk factors associated with wet macular degeneration.

While there is no cure for wet macular degeneration, there are several viable treatments for the eye disease. These include: 

• laser therapy;
• photodynamic therapy;
• macular translocation surgery;
• Anti-VEGF drugs such as Macugen, lucentis and Avastin;
• implantable optical devices

It is imperative to have regular eye examinations, especially if you have had a family member diagnosed with macular degeneration. The key to effective treatment of wet macular degeneration is early detection of the eye disease.