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Macugen granted U.S. marketing approval for wet AMD treatment
Eyetech is working on a longer-lasting formulation. The drug is also being investigated for treatment of diabetic macular edema and other retinal vascular conditions.
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An antiangiogenic drug received U.S. regulatory approval for the treatment of wet age-related macular degeneration in December, according to the co-marketers of the compound. It is slated to enter the market in the first quarter of this year.
Macugen (pegaptanib sodium injection, Eyetech Pharmaceuticals, Pfizer Inc.) is the first antiangiogenesis drug approved for the treatment of all types of neovascular AMD, regardless of lesion subtype or size, according to a joint press release from Eyetech and Pfizer.
Macugen is also the first drug for AMD to specifically target vascular endothelial growth factor (VEGF), a protein that is involved in the formation of neovascularization, the hallmark of wet AMD, said David R. Guyer, MD, chief executive officer of Eyetech Pharmaceuticals.
A simulation of normal vision (top) and vision with AMD. Images: National Eye Institute, National Institutes of Health |
The drug is a synthesized aptamer of a single RNA strand, which targets VEGF-165, one of the isoforms of VEGF, and binds to it, thereby inactivating it, according to Eyetech documents.
“I think Macugen is a novel treatment based on elegant science that for the first time targets the underlying cause of the disease, which has led to our broad AMD label including all lesion subtypes and sizes,” Dr. Guyer said in an audio conference after the approval.
He said there are 15 million people in the United States with some form of AMD, and more than 1.6 million of them have the active blood vessel growth and leakage that characterizes neovascular AMD. Those numbers are expected to increase with the aging of the baby boomer generation, Dr. Guyer said.
“Macular degeneration is an important, urgent unmet medical need and is the leading cause of irreversible severe vision loss in developed countries. We are excited to provide patients with the first targeted antiangiogenesis therapy for the eye,” he said.
Dr. Guyer said Eyetech has developed an access program to help ensure coverage of the drug for patients who might not otherwise be able to afford it.
Eyetech also is investigating an extended formulation of Macugen to reduce the number of injections needed. The company is also evaluating the drug’s therapeutic effect in patients with diabetic macular edema (DME) and retinal vein occlusion.
Eyetech co-promotes the drug with Pfizer. According to company information, Eyetech will market the drug to the retinal specialists, while Pfizer will market it to general ophthalmologists and optometrists.
Company officials said they are seeking approval for Macugen from European and Canadian regulators, and “bridging studies” are under way for regulatory approval in Japan.
A foundation therapy
Because Macugen is applicable to all subtypes and lesion sizes of neovascularization, Dr. Guyer called the drug “a foundation therapy.” He said it may be effectively combined with other therapies. How Macugen will react with other therapies, however, cannot be determined yet from current clinical experience, he said.
“What’s important about our clinical trials and our broad labeling is that Macugen is effective for all AMD subtypes and sizes. That means foundation therapy,” Dr. Guyer said. “That’s what our trials show again and again. It’s consistent with the elegant science that VEGF is an underlying cause of neovascular AMD. Given that, of course, people will be looking at combination therapy.”
Dr. Guyer said he expects investigators and companies in the industry will now pursue studies of other therapies in combination with Macugen. He said the studies that have been done to date of Macugen in combination with photodynamic therapy or steroids are anecdotal and should be followed with caution. The studies have been small and without controls, he said. Because intravitreal steroid injection has been linked to the development of cataract and glaucoma, he said he believes Macugen alone is safer than in combination with that type of therapy.
Physician compliance
In clinical trials, three doses of pegaptanib were evaluated in patients. All three levels evaluated (0.3 mg, 1 mg and 3 mg) were shown to limit the progression of vision loss from AMD in comparison to control patients. (The results of these clinical trials were, coincidentally, just published in the New England Journal of Medicine. For more on their results, see accompanying article.)
In the clinical studies, the drug was found to be effective over a 2-year course, Dr. Guyer said.
“Macugen had an approximately 50% treatment effect compared to controls in preventing severe vision loss and progression to legal blindness in the study and mean vision in patients with AMD in clinical trials,” he said.
Eyetech’s labeling recommends that physicians administer 0.3 mg of Macugen by intravitreal injection every 6 weeks, for a total of nine injections over 1 year. The labeling also recommends that biomicroscopy may be performed 2 to 7 days after the injection.
Dr. Guyer said that physicians the company has met with have understood the importance of compliance to achieve efficacy of the drug.
“I think we’ve shown that AMD is a chronic disease, and our patients who were treated for 2 years did better than patients on 1 year of Macugen. The compliance for year 1 and 2 was approximately 90%,” Dr. Guyer said. “We recently had a peer meeting where it was well-understood and advocated by these important retinal [physicians] that this is a treatment regimen similar to an antibiotic or cancer regimen and that the result of these clinical trials are predicted by the number of injections.”
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Reimbursement expected
Administration of Macugen will be reimbursed by Medicare in two parts, Dr. Guyer said, a payment for the service and a payment for the cost of the drug. The procedure will be reimbursed at $202; the CPT code is 67028. Additionally, Medicare will initially reimburse 95% of the average wholesale price of the drug under the miscellaneous code J3490. The drug should have its own code by 2006, he said.
Eyetech and Pfizer have set the price per injection at $995. After an initial period, Medicare will reimburse the drug at the average wholesale price plus 6%, Dr. Guyer said. He said Eyetech expects that private insurance carriers will also cover the procedure.
Paul G. Chaney, chief operating officer of Eyetech, said Eyetech and Pfizer are working to ensure reimbursement for physicians and to avoid denial of claims. He said some claims for Visudyne administration have been denied because of unclear coverage policies.
“Visudyne was really the first drug administered in the office of ophthalmologists in a broad way. The critical factor here in terms of risk for physicians is more denied claims – that they give the treatment to patients they believe are eligible and at some point down the stream there’s a denial of coverage,” Mr. Chaney said.
Dr. Guyer said Macugen’s broad labeling will help ensure that coverage policies are clear.
“The key here is that when you have an unambiguous label, the risk [of denial] goes down substantially. You know exactly what it’s covered for, and you know what the payers are going to reimburse,” Dr. Guyer said. “We think the label we have for Macugen is the critical piece to make sure that physicians are not left holding the bag, [with] denied claims or coverage policies that are not favorable to patients who deserve it.”
Eyetech and Pfizer have also developed the Macugen Access Program (MAP) to help ensure coverage for physicians and help underinsured and uninsured patients obtain access to the drug. Dr. Guyer said the program will begin soon.
“We put together an access program that includes … extended terms for the physicians, so that they can be sure of getting reimbursement prior to the bill for the product becoming due. We also have a comprehensive program that helps to pre-verify patients for coverage prior to receiving treatment, as well as to assure there is access to patients who are underinsured or uninsured,” Dr. Guyer said.
Mr. Chaney said the company expects the Medicare copayment for patients to be 20% of the drug’s price. He said an estimated 15% of patients do not have a form of secondary coverage to reimburse them for the copay amount, either through an employer, a Medigap policy or Medicaid.
“That’s the reason we have the access program in place for those patients, for that 20% is high. [The MAP program] will ensure that they will not be overburdened if their physician believes they are eligible for treatment,” he said.
Extended formula in development
Anthony P. Adamis, MD, Eyetech’s chief scientific officer and vice president of research, said the company is working on an extended-release form of Macugen.
“Macugen can be formulated into microspheres, and you can get zero-order kinetic release over long periods of time and get very nice levels in the eye. It’s something we’re interested in … but we haven’t released any timelines or specifics beyond that,” he said.
The efficacy of Macugen for the treatment of DME and retinal vein occlusion is also being investigated, Dr. Guyer said.
“There are many diseases in the eye that are due to abnormal blood vessel growth and enhanced permeability,” he said. “Since Macugen is such a good antipermeability, antiangiogenic agent, both Eyetech and Pfizer plan on expanding the Macugen franchise.”
Investigation of Macugen’s effectiveness against DME will be first, Dr. Guyer said, because it is a relatively common condition.
“That’s the leading cause of vision loss from diabetes, and that’s only one form of diabetic retinopathy where Macugen may prove effective,” he said. “Our phase 2 results showed positive visual as well as imaging data that we felt was very important proof of principle in this important disease.”
Eyetech and Pfizer are partners in the marketing of Macugen. With the drug’s approval, Pfizer will pay Eyetech a $90 million license fee payment, according to the joint press release from Eyetech and Pfizer.
For Your Information:
- David R. Guyer, MD, Paul G. Chaney and Anthony P. Adamis, MD, can be reached at Eyetech Pharmaceuticals Inc., 3 Times Square, 12th Floor, New York, NY 10036; 212-824-3100; fax: 212-824-3101; Web site: www.eyetech.com.
- Pfizer Inc. can be contacted at 235 E. 42 St., New York, NY 10017; 212-733-2323; Web site: www.pfizer.com.
- Jeanne Michelle Gonzalez is an OSN Staff Writer who covers all aspects of ophthalmology, specializing in practice management, regulatory and legislative issues. She focuses geographically on Latin America.