at press time

Acuity Has New Approach to AMD
Its Drug is Designed to Shut Down VEGF Production.

Founded less than 2 years ago, Acuity Pharmaceuticals appears to be a David against several Goliaths in its efforts to bring a new treatment for wet AMD through clinical trials and into the marketplace. However, Acuity believes it has an advantage over its larger rivals because its drug prevents the production of the protein that causes choroidal neovascularization (CNV), while other treatments bind the protein after it's been produced.

"Our drug, Cand5, basically shuts down the main stimulus for the disease," says Michael Tolentino, M.D., assistant professor of ophthalmology at the University of Pennsylvania and co-founder and chief medical adviser for Acuity. "Cand5 shuts down the production of vascular endothelial growth factor (VEGF), a central player in the development of CNV, and actually suppresses VEGF before it's made. Other anti-VEGF drugs use a protein antagonist to bind VEGF."

Dr. Michael Tolentino

Dr. Tolentino says the ability to attack the cellular machinery that produces VEGF gives Cand5 a major therapeutic advantage.

"Once the VEGF proteins are produced, it takes one molecule of medicine to inactivate one molecule of VEGF," he notes. "With Cand5, one molecule of the drug can shut down the production of thousands of potential VEGF proteins."

Thus far, Acuity has had significant statistical success in a primate model of macular degeneration in which CNV was induced in eight adult cynomolgus monkeys. A small Phase I human trial is expected to begin later this year.

"The drug will initially be administered through an intravitreal injection," says Dr. Tolentino. "It's a very potent drug, but because it's synthesized from a naturally occurring substance, ribonucleic acid (RNA), we don't expect to see much in the way of side effects. There were no adverse effects in the primate model."

Dr. Tolentino says the small-molecule drug could eventually be administered as an eye drop.

"Most of the other anti-VEGF drugs currently being developed started out as treatments for cancer," says Dr. Tolentino. "Acuity set out to design drugs specifically to treat AMD and diabetic macular edema. We believe Cand5 can be used alone or, eventually, in combination with other treatments.

Acuity, based in Philadelphia, is currently raising venture capital funding, but is open to a partnership with a large pharmaceutical company once it has accumulated additional clinical data. The company is headed by Dale Pfost, Ph.D. an experienced builder of biotech companies, and claims to have a strong intellectual property position in a category of drugs called "small, interfering RNA" or siRNA.

"I think it's an understatement to say that we're very excited about this new approach to treating AMD," concludes Dr. Tolentino.

IN THE NEWS

Fee increases for ultrasound. After hearing an appeal from the American Academy of Ophthalmology, the Centers for Medicare and Medicaid Services has approved reimbursement increases ranging from 25% to more than 100% for the following ophthalmic ultrasound codes: 76511, 76512, 76513, 76516, 76519 and 76529, which relate to A-scan and B-scan tests. The new payment schedule for these codes, which is retroactive to Jan. 1, replaces the significant across-the-board cuts contained in the 2004 Medicare Fee Schedule.

Santen anti-infective approved. Santen Pharmaceutical Co., Ltd. has received FDA approval to market levofloxacin ophthalmic solution 1.5% (Iquix), indicated for the treatment of bacterial corneal ulcer. Iquix is a fluoroquinolone active against a broad spectrum of gram-positive and gram-negative ocular pathogens. Levofloxacin's high solubility at neutral pH allows it to be formulated with a high concentration of active drug. (For more on fluoroquinolones, see the article on page 137).

AMD drug study begins. Aventis and Regeneron Pharmaceuticals, Inc. have begun a Phase I clinical trial of their VEGF Trap treatment for the wet form of AMD. The trial is a randomized, placebo-controlled, dose-escalating study with drug delivery through intravenous infusion. In preclinical studies, VEGF Trap has been shown to block the action of Vascular Endothelial Growth Factor, thereby halting the abnormal growth of blood vessels.

Avastin approved. Genentech has received FDA approval to market its Avastin therapy for the treatment of colorectal cancer. Avastin, the first antiangiogenic agent to receive FDA approval, has a similar molecular structure to Lucentis, which is currently in advanced clinical trials as a treatment for wet AMD. Lucentis is being developed by Genentech and its partner, Novartis.

Pinnacle Award winners. The American Society of Ophthalmic Administrators has given its 2004 William E. Rose, Jr. Pinnacle Award for excellence in Medicare billing practices to three practice administrators: Solo practice: Sondra Stateman, COE, CPC, CMPE, Palm Beach Eye Associates, Atlantis, Fla.; Small group practice: Chris McElvaine, Montgomery Eye Physicians, Montgomery, Ala.; Large group practice: Scott A. Bridgeman, MBA, Eye Q Vision Care, Fresno, Calif.

B&L names Levy. Brian Levy, O.D., has been appointed corporate vice president and chief medical officer for Bausch & Lomb, responsible for pre-clinical, clinical and medical affairs. In addition, Alan M. Bennett, the chief financial officer of Aetna, Inc., has joined the Bausch & Lomb board of directors.

Combining. The Vision Council of America (VCA) and the Low Vision Council (LVC) have joined forces, bringing 26 companies that provide low-vision products and rehabilitation services under the umbrella of the VCA. With the creation of a new division for the low-vision companies, the VCA now has 141 members. Since its inception in 2000, the VCA has emerged as a leading organization representing the interests of the optical industry.

Alrex study. Bausch & Lomb says that a multi-center study of 397 patients who used loteprednol etabonate ophthalmic suspension 0.2% (Alrex) for periods ranging from 1 to 4 years to treat the symptoms of allergic conjunctivitis demonstrated that the corticosteroid is safe for long-term use.

"Our study showed that patients who suffer from the signs and symptoms of ocular surface inflammation as a result of chronic allergic conjunctivitis can safely use the Alrex brand for extended periods of time with no adverse effects," said Chief Study Investigator Charles Slonim, M.D.

ASC Facility Fees Are Cut by 2%
Payments May Be Rebased After Costs Study.

As a result of the Medicare Prescription Drug, Improvement and Modernization Act passed by Congress late last year, facility fees for all procedures performed in ambulatory surgery centers (ASCs) were reduced by 2% as of April 1.

The new Medicare law essentially eliminated the inflation update for 2004, returning facility fees to the levels that were in effect prior to Oct. 1 of last year. The legislation also provided no rate updates for calendar years 2005 through 2009. But that may change, as the new Medicare law also calls for facility fees to be rebased, probably with some linkage to hospital outpatient rates, after the General Accounting Office conducts a costs study.

The Medicare bill also imposed an 18-month moratorium on the development of specialty and surgical hospitals, the result of a vigorous campaign by the hospital industry.

Although this action has no direct impact on ASC development, Michael Romansky, a partner in the Health Law Division of McDermott, Will & Emery, and an attorney representing the Outpatient Ophthalmic Surgery Society (OOSS), said attempts by the hospital industry to thwart the development of ASCs is "very troubling." He said hospital industry lobbyists are asking states to consider restrictions on ASC development, ranging from state self-referral restrictions to provider taxes being imposed on ASCs. Romansky said the ASC community is fighting these efforts.

In news unrelated to the Medicare bill, the Medicare Payment Advisory Commission (MedPAC), a research arm of Congress, is now recommending the elimination of the list of approved procedures that can be performed in ASCs. Instead, MedPAC says CMS should create a list of only those procedures that won't be covered if furnished in the ASC setting, rather than identifying those procedures that are suitable to be performed in ASCs.

REFRACTIVE SURGERY UPDATE

TV ad for Zyoptix. Bausch & Lomb is now using a television advertising campaign for its Technolas 217z Zyoptix System for personalized laser vision correction. The 30-second spot, part of an overall $20 million campaign for several key B&L products, shows a woman who's frustrated with the inconveniences associated with wearing eyeglasses. She then visits a surgeon certified to use the Zyoptix system while a narrator explains the precise, wavefront diagnostics that result in excellent outcomes. The commercial ends by showing the woman without glasses as her husband explains how thrilled she is with her improved vision.

Blade lawsuit settled. Bausch & Lomb and Oasis Medical have agreed to settle a lawsuit involving microkeratome blades. Under the terms of the agreement, Oasis will stop manufacturing and selling blades for the Bausch & Lomb Hansatome microkeratome, but will license B&L technology to manufacture blades for non-Bausch & Lomb microkeratomes. In addition, B&L has purchased a microkeratome blade patent issued to Oasis Medical and has also licensed Oasis blade-manufacturing technology.

CLARIFICATION

The March issue article titled "Issues in Custom LASIK: Quality of Vision" listed the FDA-approved ranges of correction for the VISX CustomVue and Bausch & Lomb Zyoptix wavefront-guided laser platforms. It did not list the ranges the platforms are capable of treating at the discretion of the surgeon. Those ranges are: up to -7.75D spherical equivalent and up to -3.50D of cylinder for Zyoptix, and up to -6.50D spherical equivalent and up to 3.50D of cylinder for CustomVue.

Making the FDA Approval Process Work
Dr. Weiss Balances Interests of Several Constituencies.

In addition to being a distinguished ophthalmologist in her own right, Jayne S. Weiss, M.D., chairs the FDA Ophthalmic Devices Panel. She's one of seven regular voting members of the panel charged with advising the FDA on whether new and innovative eyecare technologies should be approved for general use.

Originally nominated as an advisory committee consultant to the panel in 1999, Dr. Weiss became a voting member in 2000, and in 2002 was asked by the FDA to serve as chair of the panel. Like all voting members, she will serve a 4-year term. Currently, the panel is made up of five ophthalmologists, a vision scientist and an optometrist. In addition, the panel is assisted by a pool of 36 consultants who are called in on an individual basis when specialized expertise is needed to decide on a Pre-Market Application for a specific product. Consultants called in on a specific application can vote on that application.

Because the FDA generally relies on the panel's recommendations, panel members have a major influence on which new products reach the public and which are rejected or sent back for further development and testing. In most cases, millions of dollars in product development costs and future sales are at stake.

"I enjoy doing my part to help make sure that the process serves the consumer, the physician and the company," says Dr. Weiss, a specialist in corneal and refractive surgery and director of refractive surgery and ophthalmic pathology at the Kresge Eye Institute, Wayne State University, in Detroit. "I'm pleased when devices that demonstrate reasonable safety and efficacy are approved (with or without conditions) by the panel."

Though Dr. Weiss finds approving new products that will improve patients' quality of life highly rewarding, she says that service on the panel also has its frustrations.

"I'm a bottom-line type of person," she says. "I sometimes get frustrated when I have to wade through 'spin' to get to the real data. Ultimately, the data always speak for themselves."

Dr. Weiss says serving on the panel has given her a more accurate view of the capabilities and limitations of technology. And she has high praise for the professionalism and skills of the FDA staff members with whom she works.

	Dr. Jayne S. Weiss

"The FDA personnel have consistently demonstrated their knowledge and genuine interest in expediting the approval process," notes Dr. Weiss.

"I also try to ensure that we apply the least burdensome provisions to the company," she adds. That is, we should only require extra studies if they're directly needed to prove the device reasonably safe and efficacious."

Does she think that ophthalmology is in a "golden age" of technological advances?

"There are certainly larger numbers of technological options being made available, especially to the refractive surgery patient. Whether or not this turns out to be a golden age will best be determined retrospectively a decade or more down the line."