at press time

Drug Investigators' Ethics are Questioned
Report: Wall Street Firms Paid for Lucentis Information.

Some investigators involved in clinical trials for important new drugs — including the pivotal phase 3 trials of Lucentis for wet AMD — were paid an average of $300 to $500 an hour by Wall Street firms to provide insights into the drug's safety and effectiveness. These revelations came to light in August in a major article in the Seattle Times and brought immediate calls for the Securities and Exchange Commission (SEC) to look into the practice.

One of the key findings of the article is that the investment firm Citigroup Smith Barney talked to 26 ophthalmologists, many of whom were involved in the clinical trials for both Lucentis and its key competitor, the recently approved AMD therapy Macugen.

"The doctors were able to give Smith Barney valuable comparative information," the article states.

Smith Barney then summarized the information it had gathered on Lucentis in a report to select investors on May 5 of this year, predicting that 97% of patients given Lucentis would have stable or improved vision. When the drug's developer, Genentech, released results of its phase 3 MARINA study of Lucentis on May 23, the article states that Smith Barney's numbers "were almost exactly on the money."

The phase 3 results (which were almost identical to the publicly available phase 1 and 2 results published by Ophthalmology Management in 2003) indicated that 95% of Lucentis patients had stable or improved vision. This news led to an immediate 40% drop in the price of the shares of Eyetech Pharmaceuticals, the developer of Macugen. The article omitted any mention of the phase 1 and 2 Lucentis data, which investigators were free to discuss publicly.

"Any hedge fund or other investor who had acted on Smith Barney's research by betting against Eyetech would have made better than a 40% return in just 3 weeks," the article noted.

The investigators who spoke to Smith Barney insisted that they did not reveal confidential information or valuable details. They contend that they provided only their personal impressions of how the drug was working.

"If you treat 20 patients you can get a sense of where a trial is going," one ophthalmologist told the Seattle Times. Another ophthalmologist said he was just asked to give his "gut feelings" on the effectiveness of Lucentis.

However, Arthur Caplan, M.D., director of the Center for Bioethics at the University of Pennsylvania, said investigators being paid to provide insights to Wall Street constituted "a moral cesspool."

Sen. Charles Grassley (R-Iowa), head of the Senate Finance Committee, which oversees the financial markets, asked the SEC to look into Wall Street payments to drug investigators. The SEC indicated it would do so.

"Selling drug secrets violates a trust that is fundamental to the integrity of both scientific research and our financial markets," said Sen. Grassley.

In addition to the revelations regarding ophthalmologists, the newspaper article also reported on payments to physicians involved in clinical trials for cancer drugs.

Microkeratome Usage Decreases
IntraLase and Surface Ablation Make Gains.

Theodore Huber, an analyst who covers eyecare stocks for Wachovia Securities, reports that a Market Scope survey and feedback from refractive surgeons show considerable progress recently by IntraLase and the range of surface ablation procedures. He notes that where microkeratomes were used in nearly 95% of excimer laser refractive procedures 2 years ago, that share is down to about 75% today and appears to be falling at an accelerated rate.

IntraLase recently reported that its technology now accounts for about 18% of all corneal flaps cut in the United States, up from 16% at the end of 2004.

Corporate laser center TLC's conversion of nearly 14% of its centers to IntraLase in a 7-month timeframe is a meaningful data point, Huber says.

He also notes that during LCA Vision's earnings conference call in late July, company management commented that it is re-evaluating IntraLase for creation of LASIK flaps. To date, LCA Vision has not purchased an Intralase laser. During the call, management indicated that its medical advisory board is evaluating IntraLase's new 30 Khz laser given its faster procedure time and less "sticky" LASIK flap bed.

Management indicated that any decision to adopt IntraLase would require "clinical data showing superior outcomes" vs. microkeratome LASIK. IntraLase users have reported superior outcomes, though little is published in peer-reviewed forums and no study compares IntraLase to the latest generation of microkatomes, such as the new devices launched by Advanced Medical Optics and Bausch & Lomb this year. Huber said that new clinical data on IntraLase's 30 Khz laser should be released at the upcoming American Academy of Ophthalmology meeting.

With no placements at LCA Vision, and still-limited penetration of TLC Vision sites, Huber says that IntraLase is underrepresented among corporate laser centers, the fastest-growing segment of the domestic LASIK business. With its growing installed base (LCA Vision currently operates 42 centers) and procedure share gains, LCA Vision represents an important potential customer, Huber notes. "The statements from management significantly increase the likelihood that LCA Vision will buy an IntraLase unit in the next year, in our view," Huber concludes.

OSI Pharmaceuticals Will Buy Eyetech
Stockholders of Macugen Developer Will Get $20 a Share.

Eyetech Pharmaceuticals, the developer of the FDA-approved drug Macugen for wet AMD, has agreed to be acquired by OSI Pharmaceuticals for about $935 million in cash and OSI stock. The deal is valued at about $20 for each share of Eyetech, $15 of it in cash.

The offer represents a premium of 43% over Eyetech's Aug. 19 closing price of $13.99 a share. Eyetech shares had traded as high as $49 in the past 12 months, but the stock plummeted when highly impressive phase 3 clinical trial results from Lucentis, a potential competitive treatment, were released in late May. Lucentis is being developed by biotech giant Genentech.

This is OSI's initial venture into the area of ophthalmic drugs. Until now, OSI has focused on treatments for cancer and diabetes. OSI's flagship product is Tarceva, which has been approved by the FDA for the treatment of advanced non-small cell lung cancer. Tarceva is also currently being reviewed by the FDA as a potential treatment for pancreatic cancer.

As Ophthalmology Management went to press, it was unclear how Pfizer, Eyetech's marketing partner for Macugen, would react to the proposed deal. Pfizer owns about 8.3% of Eyetech stock, some of which Pfizer purchased for prices as high as $43.60 a share.

In The News

Tecnis acrylic approved. Advanced Medical Optics, Inc., (AMO) says the FDA has approved the Tecnis IOL on an acrylic platform. The company says the Tecnis foldable acrylic IOL offers surgeons and their patients the same unique benefits as the Tecnis silicone IOL. AMO says it is the only company to market IOLs with a claim approved by the FDA for reduced spherical aberration and improved functional vision, particularly for night driving.

Improved crystalens. Eyeonics, Inc., the developer of the crystalens, has introduced the crystalens SE system. The new system offers three main features. First, eyeonics has extended the square edge on the current crystalens design to 360° to facilitate capsular bag maintenance and to inhibit lens epithelial cell migration.

In addition, cycloplegia, or paralysis of the ciliary muscles postoperatively, has been found to be unnecessary in recent clinical evaluations. Visual outcomes and accommodation consistent with crystalens' FDA clinical trial results were accomplished without the use of a cycloplegic agent in these evaluations.

The new lens has also been validated for use with the STAAR Indigo Injector System. Eyeonics says the injector will allow surgeons to utilize a smaller, sub–3-mm incision, and also provide for a more sterile insertion because the cartridge precludes the need for handling the lens directly.

HRT3 debuts. Heidelberg Engineering GmbH, a leading developer of laser diagnostics for ophthalmic applications, has introduced the Heidelberg Retina Tomograph 3 (HRT3), a newly enhanced version of its flagship product for the assessment, diagnosis and management of glaucoma.

Like its predecessor, the HRT2, the HRT3 uses laser technology to produce a topographical image of a patient's optic nerve, providing an objective analysis of the structure's cup, rim and retinal nerve fiber layer.

Macugen earns award. Macugen, which was launched early this year by Eyetech Pharmaceuticals and Pfizer as a newly approved treatment for wet AMD, was named Innovative Pharmaceutical Product of the Year at the recent 2005 Pharmaceutical Achievement Awards.

Help for keratoconus. Addition Technology, Inc., the manufacturer of Intacs prescription inserts for the treatment of myopia and keratoconus, has formed The Foundation for Keratoconus Care to provide financial support to patients who cannot afford an Intacs procedure to treat keratoconus.

The Foundation will provide a patient assistance program that counsels patients on their clinical options, including the selection of primary and surgical eyecare practices. The Foundation also will make grants to support clinical research on the disease.

"Frequently, we receive inquiries from ophthalmologists and optometrists on behalf of patients who are ideal candidates for the Intacs procedure, but who do not have the financial wherewithal nor adequate healthcare coverage to afford the cost of the procedure," said William M. Flynn, president and chief executive officer of Addition Technology. "We felt we needed to put a long-term solution in place." "In the past, we have provided Intacs to surgeons free of charge for these patients, but we felt we needed to put a more permanent and long-term solution in place that also recognizes the primary care aspect of keratoconus care."

Visian ICL is "approvable." STAAR Surgical Company said the FDA has reviewed the company's pre-market approval application (PMA) for the STAAR Myopic Visian phakic IOL and has determined that the PMA is approvable subject to an FDA inspection that finds the company's manufacturing facilities, methods and controls in compliance with the applicable requirements of the FDA's Quality System Regulation. For more than 1 year, STAAR has been attempting to correct deficiencies cited by the FDA at the company's Monrovia, Calif., manufacturing facility. The company believes it has made major progress in correcting the problems cited by the FDA.

The Visian is a refractive phakic implant intended for placement in the posterior chamber of the eye. The models of the STAAR Myopic Visian subject to the PMA are indicated for correcting myopia ranging from -3 D to -15 D with astigmatism less than or equal to 2.5 D at the spectacle plane, and for reducing myopia in adults with myopia ranging from greater than -15 D to -20 D with astigmatism less than or equal to 2.5 D at the spectacle plane.

The Visian is indicated for patients 21 to 45 years of age with anterior chamber depth 3 mm or greater, and a stable refractive history within 0.5 D for 1 year prior to implantation.

Currently, the only phakic IOL approved by the FDA is the Verisyse, developed by Ophtec and marketed by Advanced Medical Optics.

Japan approves EpiLift. Advanced Refractive Technologies (ART), formerly known as VisiJet, a developer and marketer of innovative technologies for the ophthalmic surgical market, has received approval from the Health Ministry of Japan to market and sell its EpiLift System for epi-LASIK.

CORRECTION

Portions of the listing for Micro Medical Devices PalmScan P-200 FastPach were missing from the Pachymeters section of the Diagnostic Instrument Buying Guide, which was distributed with the July issue of Ophthalmology Management. Here is the listing as it should have appeared:

Company: Micro Medical Devices

Model: PalmScan P-200 FastPach

Price: $2,295

Warranty: 1 year

Type: Handheld

Weight: 10 oz.

Range: 12μm to 1200μm

Calculator: Yes

Portability: Yes

Source: Dual rechargeable batteries

Additional Features: More than 200 scans per charge; corneal waveform display; Wi-Fi/IR printing; high-res color touch-screen controls.