B & L Implant Approved for Uveitis
Retisert Can Deliver Drug for 30 Months.
Bausch & Lomb's single-indication orphan drug Retisert (fluocinolone acetonide intravitreal implant) has been approved for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye. The sight-threatening inflammatory disease primarily afflicts people between the ages 20 and 50.
Retisert is the first intravitreal drug implant for the treatment of a condition that affects an estimated 175 000 people in the United States and approximately 800 000 people worldwide. The product received Food and Drug Administration (FDA) Fast Track status, which allows priority review of a drug intended for an unmet medical need, and an FDA Orphan Drug designation for the uveitis indication. B&L is targeting a mid-year launch of the product.
The Retisert implant is about the size of a grain of rice.
Bausch & Lomb's patented drug-delivery microtechnology in Retisert consists of a tiny drug reservoir designed to deliver sustained levels of the anti-inflammatory corticosteroid fluocinolone acetonide for approximately 30 months directly to the back of the eye.
"I believe that with its unique drug-delivery technology, Retisert will offer an efficacious treatment for this chronic, severe blinding disease," said Glenn J. Jaffe, MD, professor of Ophthalmology and director of the Uveitis Service at Duke University Eye Center, Durham, NC.
"Retisert represents a major therapeutic advance in treating posterior segment uveitis. It provides an effective treatment for this condition, and has allowed my patients who required long-term steroids or immunosuppressive therapy to avoid the complications of these systemic medications," added Daniel F. Martin, MD, Thomas M. Aaberg professor of Ophthalmology at Emory University in Atlanta and director of the Retina Service at Emory Eye Center.
FDA approval of the drug was based on 34-week results from two 3-year randomized, double-masked, multicenter clinical studies demonstrating that in eyes with Retisert there was:
A a statistically significant decrease in the recurrence of uveitis from approximately 40% to 54% for the 34-week period pre-implantation to approximately 7% to 14% for the 34-week period post-implantation
A a statistically significant decrease in the use of adjunctive therapy including systemic corticosteroid and/or immunosuppressive therapy from approximately 47% to 63% at the time of implantation to approximately 5% to 10% at 34 weeks post-implantation, and for patients needing periocular corticosteroid injections from approximately 50% to 65% for the 34-week period pre-implantation to approximately 3% to 6% for the 34- week period post-implantation
A statistically significant improvement of 3 or more lines of visual acuity in approximately 19% to 21% of study eyes at 34 weeks post-implantation.
The most common adverse events, which were anticipated given the nature of the disease and the type of drug used, include cataract progression, which is managed by standard cataract surgery; increased intraocular pressure, which is managed with the use of IOP-lowering eye drops or filtering surgery, procedural complications, and eye pain.
AMD information. Novartis Ophthalmics said that the Visudyne Access Network (VAN) is now available to patients with wet AMD and their retina specialists nationwide. The network provides a package of services designed to improve access to educational information, simplify reimbursement issues, and ultimately improve outcomes in patients diagnosed with wet AMD.
"The number of cases of wet AMD is expected to nearly double by the year 2020, and a relatively small community of retina specialists is faced with providing comprehensive ophthalmic treatment for this large and growing patient population," said Quinton Oswald, head of Novartis Ophthalmics North America. "Some of the components of VAN have existed for some time; by packaging them, we are ensuring that more specialists are aware of them and avail themselves, and their staffs, of our services as disease management for these patients takes a greater role in their practices."
CMS to Review High-Volume Codes
AAO Says Move is Arbitrary; Promises to Fight
The American Academy of Ophthalmology (AAO) has expressed outrage at a decision by the Centers for Medicare and Medicaid Services (CMS) to target key high-volume ophthalmology codes for the upcoming 5-Year Review of Work Values. The AAO says the potential impact of this decision on ophthalmology payments is enormous. Some of the targeted codes are:
- YAG capsulotomy
- cataract with IOL
- vitrectomy with epiretinal membrane stripping
- photodynamic therapy
- laser PRP
- fundus photography
- flourescein angiography
- visual fields.
"The list of codes CMS has decided to review appears arbitrary," said Michael Repka, MD, Academy secretary for Federal Affairs. "With all the codes that have never been included in a 5-Year Review, we question why CMS targeted some ophthalmology codes that have already been reviewed through this process. No reason is given for these decisions. CMS just appears to have targeted high-volume codes. All of organized medicine is upset by CMS's lack of rigor.
"If the work value and time needed to provide cataract surgery are cut, it will negatively impact all other ophthalmic codes because of its effect on the practice-expense methodology," Dr. Repka added.
In a 5-Year Review, CMS creates a list of codes it believes are overvalued or undervalued. It also seeks input from medical specialties in identifying codes. The list is then submitted to the AMA/Specialty RVS Update Committee (RUC), a physician panel that weighs the relative value of physician work involved in these procedures. For this review, CMS has targeted 14 ophthalmology codes as overvalued. The list also includes 15 undervalued codes submitted by the Academy, bringing the total number of ophthalmology codes up for review to 29. The Academy's Health Policy Committee, with input from ophthalmic specialty societies, put the undervalued list together following a year of research.
The Academy will fight for all 29 ophthalmic codes before the RUC. Surveys on these codes will be sent to selected Academy members this month. The data will be used to support the argument for increasing and/or maintaining the value of these codes. A complete list of ophthalmology codes up for review is posted on the AAO Web site: www.aao.org.
The RUC will review the codes and make recommendations on new values to CMS in September. CMS will then publish a proposed rule in the spring of 2006 for comment. Final values will be published in November 2006, with implementation in January 2007. CMS typically accepts 96% of RUC recommendations.
Cancer drug tried in AMD. The University of Miami's Bascom Palmer Eye Institute said early results from the Systemic Avastin for Neovascular Age-Related Macular Degeneration (SANA) study showed that the antiangiogenic cancer drug Avastin (bevacizumab, Genentech) was able to substantially reduce the leakage from abnormal blood vessels in eyes of patients with wet AMD. Within 1 week, vision improvement occurred in patients treated with Avastin given through an intravenous infusion.
The SANA results were presented at the Macula Society meeting in March.
The presentation highlighted the outcomes in the first nine patients treated with Avastin through 3 months. Overall, average vision improved in both eyes because most of the patients had wet AMD in both eyes. At the beginning of the study, one eye of each patient was designated as the "study eye" and the other eye as the "fellow eye." At 3 months, the average vision improved just over 2 lines in the "study eyes" (P=.008) and just over 3 lines in the "fellow eyes" (P=.001) as measured by the number of letters used on a standard eye chart. The improvement in vision correlated with a decrease in the leakage of fluid from the abnormal blood vessels in these eyes.
"A potential advantage of Avastin over other therapies for wet AMD is that vision improvement can occur within 1 week of treatment," said Philip J. Rosenfeld, MD, PhD, associate professor of ophthalmology at Bascom Palmer Eye Institute and the principal investigator of this clinical trial. "In addition to the improved vision, Avastin causes a reduction in leakage from the abnormal blood vessels, and we observed a restoration of normal macular anatomy."
Avastin was approved by the Food and Drug Administration last year for the treatment of colorectal cancer. Lucentis (ranibizumab, Genentech/Novartis) a drug that is closely related to Avastin and given intravitreally, is currently in clinical trials as a treatment for wet AMD.
Dr. Donald M.
He was a Noted Researcher.
Donald M. Gass, MD, of Nashville, Tenn., died recently after a long bout with pancreatic cancer. He was 76.
Dr. Gass was selected as one of the 10 most influential ophthalmologists of the 20th century by his peers and inducted into the American Society of Cataract and Refractive Surgery (ASCRS) Hall of Fame in 1999. His work combined his interest in pathology with new techniques for viewing the fundus with the fundus camera and fluorescein angiography.
Dr. Gass was well known for his research on diseases of the retina, macula, and uvea, much of which was done at the University of Miami School of Medicine. In his later years, Dr. Gass continued to practice, and was a professor of ophthalmology at Miami and Vanderbilt University in Nashville.
Dr. Gass is survived by his wife, Margy Ann, and 4 children, John Donald Gass, Carlton Simpson Gass, MD, Dean MacIntyre Gass, and Media Lee Yawn.
"He contributed much to ophthalmology because of his work, his outstanding teaching, and his clinical applications. Many of us have learned a great deal from him and are thankful for it," said ASCRS president, Priscilla Arnold, MD.
MT360 improves quality of life. A study of 50 AMD patients who had macular translocation with 360-degree peripheral retinectomy (MTO360) indicates that the procedure improves overall quality of life, especially in vision-related activities such as reading, sewing and navigating around the house. Patients whose visual function was improved the most by the procedure reported the greatest improvement in their quality of life.
"We can now show, scientifically, that our patients have been able to improve not only their central vision, but their quality of life as a results of the visual improvements following MT360," said Cynthia Toth, MD, senior author of the study and associate professor of ophthalmology at Duke University Medical Center.
Researchers reached their conclusions after analyzing the data from quality-of-life questionnaires filled out by the patients both before, and 1 year after, MT360 surgery. The average age of the patients was 79.6 years.
The MT360 study findings were published earlier this year in Ophthalmology.
Subspecialty NewsGene Greatly Increases Risk of AMD
Researchers Say it May Account for 50% of Cases.
Researchers from Boston University School of Medicine (BUSM) and the University of Texas Southwestern Medical Center at Dallas (UT Southwestern) report the discovery of a genetic variation that is the strongest known risk factor associated for AMD. Published in a recent issue of the journal Science, the study entitled "Complement Factor H Polymorphism and Age-Related Macular Degeneration" details the discovery of the gene that may account for approximately 50% of the cases of AMD in the population.
The findings that implicate the complement factor H (CFH) gene in AMD have also been independently corroborated by researchers at the Yale University School of Medicine and at Duke University Medical Center. That gene helps regulate inflammation in a branch of the immune system.
"Considering that AMD is such a common and complex condition with multiple risk factors, we did not expect that we would identify a gene that is responsible for almost half of the cases," said author Lindsay A. Farrer, PhD, chief of the genetics program at BUSM, and a professor of medicine, neurology, genetics and genomics, epidemiology and biostatistics at BUSM.
The biological basis of this disorder is unclear. However, it was strongly suspected that genetics did play a role. The researchers tested single nucleotide polymorphisms (SNPs) for association of AMD in a region of 14 million base pairs on chromosome 1q25-31 where a gene for AMD had been previously localized in families with multiple persons affected with AMD. Using two independent case-control populations, the researchers found that possession of at least one copy of histidine at position 402 of complement factor H increased the risk of AMD almost threefold.
"Given the rapid aging of the population, an estimated 3 million people will have complications of AMD by the year 2020. We hope our findings will create new avenues for developing preventative and therapeutic strategies for AMD," added co-author and retina specialist Albert O. Edwards, MD, PhD, president of the Institute for Retina Research at the Presbyterian Hospital in Dallas. Dr. Edwards conducted his research while on faculty at UT Southwestern.
This research was funded by a grant from the National Eye Institute.
Pfizer acquisition. Pfizer Inc. said it plans to purchase Angiosyn, Inc., a privately held California drug development company with expertise in creating antiangiogenic agents for the treatment of ophthalmic diseases such as wet AMD.
The Angiosyn deal is tentatively valued at $527 million, plus future royalty payments if a drug is approved. Under the terms of the agreement, Angiosyn will be merged into a wholly owned subsidiary of Pfizer.
Full payment is contingent upon certain conditions, including bringing an eye treatment to market. Angiosyn is currently developing a treatment for angiogenesis, or uncontrolled blood vessel formation, which is a major factor in diseases such as macular degeneration.
The transaction is expected to close in the next few months.
Drug development deal. Novartis Pharma AG said it has executed a commercialization agreement with Schering AG, Germany, for the investigational agent PTK787, an oral angiogenesis inhibitor, which Novartis and Schering have been jointly researching and co-developing since 1995.
Novartis has obtained exclusive rights to develop PTK787 for the treatment of wet AMD. Under the agreement, Novartis will obtain full global and exclusive developmental and commercialization rights to PTK787 in ophthalmics. Novartis will pay an upfront fee, milestone payments, and royalties on ophthalmics sales. Additional details of the agreement were not disclosed.
"The wet AMD market is expected to show strong growth over the next 10 years, fueled by increased patient diagnosis and referrals with the entry of new competitors," said David Epstein, president of Novartis Oncology. "With PTK787, we are excited to explore the full potential of this next-generation compound and continue to lead innovation in the treatment of retinal diseases."
New Test Diagnoses Blinding Disease
Devic's Syndrome Often Mistaken for MS.
Misdiagnosis of a severely paralyzing disease can now be averted due to a blood test developed by Mayo Clinic researchers and their Japanese collaborators. Often misdiagnosed as multiple sclerosis (MS), neuromyelitis optica (NMO) can cause blindness.
The finding will help doctors correctly treat NMO -- also known as Devic's Syndrome -- sooner and more effectively. In some countries, misdiagnosis may be as high as 30%. Early diagnosis is important because NMO is best treated differently than multiple sclerosis. Treatment requires immune suppressive medications in the first instance, rather than the immune modulatory treatments typically prescribed for MS. Therefore, a patient who has NMO, but is misdiagnosed with MS, may not receive optimal care at the earliest possible time.
NMO affects the optic nerves and spinal cord -- and within 5 years causes half of affected patients to lose vision in at least 1 eye. Many lose the ability to walk independently. The prognosis for loss of sight and permanent paralysis is much worse for patients who have NMO than for those who have MS. The cause of NMO is unknown. If diagnosed correctly before the myelin sheath is too damaged, plasma exchange therapy and immunosuppressive medications such as azathioprine and corticosteroids can be effective in stopping the damage and restoring nerve function.
"Early diagnosis and treatment are of paramount importance to reduce the severity of the course of NMO," says Vanda A. Lennon, MD, PhD, Mayo Clinic neuroimmunologist who led the international research team. "With this biomarker, physicians are in a much better position to start optimal therapies sooner, and hopefully, lessen the impact of the disease."
It is not clear how many people have NMO, though it is generally regarded as rare in the United States. However, one Mayo Clinic physician in Rochester, MN, has seen approximately 50 cases in the last 3 years, and an equal number of variants of NMO, such as recurrent transverse myelitis and recurrent optic neuritis. Ninety percent are women from 30 to 60.
By some estimates, 1 of out of every 4 African Americans diagnosed with MS may actually have NMO instead. NMO is considerably more common in Japan and Asia, where its prevalence is about 3 per 100 000 citizens. In Japan, roughly one-third of patients diagnosed with MS-like illness may actually have NMO.
MS is not confined to optic nerve and spinal cord involvement. However, the symptoms of the two diseases overlap, and optic nerve and spinal cord involvement occur in both. NMO is particularly difficult to distinguish from MS in the early phases of the disease.
Without the new blood test, classic NMO can only be distinguished from MS by the extensive spinal cord lesions that NMO inflicts, spanning 3 or more segments of the bony spine, and by the lack of MS-type lesions, found by magnetic resonance imaging of the brain.
In developing the new test, blood samples were taken from patients in the United States and Japan and evaluated for the presence of a newly identified central-nervous system autoantibody. All antibodies are circulating proteins produced by the immune system. Unlike antibodies of healthy persons which attack invading disease organisms, an autoantibody attacks normal body constituents by a poorly understood error in immune function. This new autoantibody was discovered in the Mayo Clinic Neuroimmunology Laboratory in the course of analyzing thousands of blood samples. However, the significance of the antibody was not initially appreciated. Based on a study of one group of patients with clinically recognized NMO, the researchers discovered that this "unclassified" antibody was common among these patients and therefore useful as a diagnostic biomarker for NMO.