at press time
Oxigene Sees Promise in Wet AMD Drug
A Success Spurs Company to Expand R&D.

Oxigene, a leader in the development of vascular targeting agents (VTAs) that selectively destroy unwanted blood vessels, says it will use $24.2 million raised from a recent sale of stock to expand its research and development program in ophthalmology.

The company, which already has a small Phase I/II clinical trial under way for wet AMD, plans to begin human studies in several other degenerative retinal diseases. It's also working to develop formulations of its lead VTA, Combrestatin A4 Prodrug (CA4P), for local delivery to the eye.

Oxigene CEO Fred Driscoll

The company decided to broaden its ophthalmic program after a patient afflicted with myopic macular degeneration showed dramatic improvement after being treated with CA4P. The patient, who wasn't a participant in the wet AMD trial, was treated at the Wilmer Eye Institute of the Johns Hopkins University School of Medicine under a special FDA exemption. The 35-year-old man had 20/50 vision in the study eye with active leakage in both eyes prior to treatment with CA4P. After treatment with systemically delivered CA4P, the patient's vision had been restored to 20/20 with significantly reduced leakage in each eye.

The trial involving the intravenous delivery of CA4P for the treatment of wet AMD is also being conducted at the Wilmer Eye Institute under the direction of Peter Campochiaro, M.D., and Quan Dong Nguyen, M.D., both professors of ophthalmology at the Wilmer Eye Institute.

"We can't say much about the interim results of the wet AMD trial since we are bound by confidentiality agreements with both Johns Hopkins and The Foundation Fighting Blindness," Oxigene CEO Fred Driscoll recently told Ophthalmology Management. "It involves 15 patients in an open-label, dose-escalating study with the goal of proving safety and efficacy. We estimate that initial results won't be released until later this year by the investigators, but suffice it to say that we're pleased with the progress we're seeing to date."

CA4P is derived from a natural compound, the bark of the South African bush willow tree. The compound has been synthesized and patented by Oxigene. CA4P is called a vascular targeting agent because it targets the endothelial cells that line blood vessel walls and changes their shape from flat to round, thereby cutting off the blood flow to unwanted vessels.

CA4P has already been tested against solid tumors in about 150 cancer patients and, like some other new oncology drugs, also shows potential for treating wet AMD and other related eye diseases.

Oxigene has begun studying ways to deliver CA4P directly to the eye, with the ultimate goal of putting the small-molecule drug into an eye drop.

IN THE NEWS

B&L buying drug candidate. InSite Vision Inc., a developer of ophthalmic drugs and drug-delivery technology, has reached an agreement to sell its drug candidate ISV-403 for the treatment of ocular infections to Bausch & Lomb. ISV-403 combines a fourth-generation fluoroquinolone with InSite Vision's patented DuraSite drug delivery system.

Under the terms of the agreement, InSite Vision will receive a cash payment, reimbursement of some product development expenses, and a percentage of future ISV-403 product sales in all licensed countries. Bausch & Lomb will assume all future ISV-403 development and commercialization expenses.

Dry eye treatment. The FDA has issued an approvable letter for Inspire Pharmaceutical's diquafosol tetrasodium ophthalmic solution for the treatment of dry eye. A condition of approval is that Inspire provide an additional clinical study.

Inspire said it will meet with the FDA to determine whether a study completed after the New Drug Application was submitted will be sufficient to meet that requirement.

Distribution agreement. Johnson & Johnson Vision Care, Inc. (JJVCI) has entered into an agreement to become the exclusive U.S. distributor for three Santen ophthalmic pharmaceuticals. During the first quarter of 2004, JJVCI will take over distribution of levofloxacin ophthalmic solution (Quixin), timolol hemihydrate ophthalmic solution (Betimol) and (pemirolast potassium ophthalmic solution (Alamast).

Good place to work. Alcon, Inc. has been voted to Fortune magazine's list of "The 100 Best Companies to Work for in the United States" for the sixth consecutive year. The company, whose U.S. headquarters is in Fort Worth, Texas, has more than 6,000 employees in this country.

TTT reimbursement. Pennsylvania became the 16th state to approve reimbursement for transpupillary thermotherapy (TTT) treatment for wet AMD and certain intraocular tumors. The decision by HGSA Administrators, the Medicare Part B carrier for Pennsylvania, became effective Dec. 29. The TTT protocol primarily uses the OcuLight SLx laser by Iridex.

Acquisition. American Optisurgical Inc. has purchased the Mentor phacoemulsification line from Paradigm Medical Industries. Included in the acquisition are the Mentor SIStem and Mentor Odyssey phaco systems. The acquisition will allow American Optisurgical to offer a complete line of phaco units by adding SIStem and Odyssey to the company's Horizon Phaco unit.

Grant awarded. Fight for Sight, which provides grants for ophthalmic research, has awarded $7,500 to the Inter-Mountain Ocular Research Center at the Moran Eye Center of the University of Utah to support its program for analyzing the causes of postoperative endophthalmitis and inflammation following anterior segment surgery.

STAAR Surgical Gets FDA Warning Letter
ICL Not Involved, but Approval Could Be Delayed.

STAAR Surgical Company had appeared on track to receive early FDA approval of its Implantable Contact lens (ICL), the first phakic IOL to be approved by the FDA Ophthalmic Devices Panel. But STAAR now faces a potential delay in launching the ICL.

The obstacle arose in the form of an FDA "Warning Letter" citing STAAR's "significant deviations" from federal quality regulations. Though the violations don't directly involve the ICL, the device can't be approved until STAAR resolves its problems with the FDA.

ICL approval may be delayed.

The violations, discovered during an FDA inspection of STAAR's Monrovia, Calif., manufacturing facility last year, fall into two major areas:

Failure to adequately report complaints concerning problems with IOLs used in cataract surgery. Under federal Medical Device Reporting (MDR) procedures, companies are required to file written reports with the FDA of any serious injuries or malfunctions associated with a medical device. The FDA says STAAR failed to report some events.

Failure to follow established procedures for approving an outside testing laboratory. The FDA said the methods used by the laboratory to test raw materials and finished devices hadn't been validated.

"You should take prompt action to correct these deviations," the FDA letter advised. "Failure to promptly correct these deviations may result in regulatory action being initiated by the FDA without further notice."

In response to the letter, STAAR said it's "committed to invest the resources required to do whatever is necessary to implement the corrective actions identified."

STAAR management said it believes the costs of implementing corrective actions won't be great and that the issues can be resolved "in a reasonable time frame."

STAAR also emphasized that the complaints concerning injuries and product malfunctions pertained to IOLs used in cataract surgery and not to the ICL for myopia.

Diet, Weight Affect AMD Progression
Researchers Finding Many Factors Influence the Disease.

People afflicted with AMD whose diets are high in fat are at higher risk of the disease progressing to the advanced stages associated with visual loss, report researchers at the Massachusetts Eye & Ear Infirmary in Boston. The research team, led by Johanna M. Seddon, M.D., ScM., also found that a diet high in nuts and fish reduces the risk of disease progression.

The study, originally reported in the Archives of Ophthalmology, involved 261 patients who were at least 60 years old and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least one eye. Average follow-up period was 4.6 years.

Saturated, monounsaturated, polyunsaturated and transunsaturated fats were related to disease progression. Food groups with higher levels of these fats, particularly processed baked goods, were also associated with a higher rate of progression, the authors found.

"Dietary intake of fat, including specific types of fat as well as fat-containing foods, is a potentially important behavior that can modify the outcome for patients who already have the early or intermediate forms of AMD," the authors concluded.

In an earlier study published last year, Dr. Seddon and associates reported that overweight and obese AMD patients were at greater risk for AMD progression than patients with lower body weight. The study found that disease progression in overweight patients occurred nearly twice as fast as in patients with lower body weight.

The researchers also found that AMD patients who participated in vigorous exercise at least three times a week saw a reduction in disease progression.

"Right now, we know that some of the same risk factors for heart disease -- smoking, obesity and lack of exercise -- also affect the progression of AMD," noted Dr. Seddon.

Refractive Surgery Update

Refractec expects approval. Refractec, Inc., the developer of the conductive keratoplasty (CK) vision correction procedure, said it anticipates FDA approval of its CK Blended Vision procedure for patients with presbyopia in early 2004. CK has already been approved for the correction of age-related hyperopia.

Refractec said it's also expanding and standardizing its physician training program, and expects to have more than 450 ophthalmologists offering CK by the end of the first quarter of this year.

The company noted that CK has become the fastest-growing new refractive procedure since the introduction of LASIK, capturing 14% of the U.S. refractive market in CK's approved range.

Intralase placements rise. Intralase Corp., which manufactures ophthalmic lasers used to cut the corneal flap in laser vision correction procedures, reported the placement of 26 Intralase FS lasers in the 3 months ended Dec. 31, bringing its number of 2003 laser placements to 67.

The Intralase was used in 27,372 procedures in the December quarter, an increase of 136% over the comparable quarter a year ago. Industry analysts estimate that Intralase is now being used in about one-fourth of all laser vision correction procedures performed in the United States.

Nidek software gets CE Mark. Nidek Co. Ltd. said it has received the CE Mark for its Customized Aspheric Treatment Zone (CATz) software for its Nidek EC-5000 Excimer Laser System. The approval clears the way for Nidek to market its laser and custom treatment algorithm throughout the European Union for the correction of myopia with or without astigmatism.

Nidek says CATz uses a proprietary ablation algorithm based on topography data that employs smooth treatment zones to create a seamless transition from the treated to the untreated cornea. Clinical data submitted to gain CE Mark approval showed 93% of patients having an uncorrected visual acuity of 20/20 or better. Ninety-seven percent of patients were within 0.50 diopters of the targeted refractive correction, and root mean square values of all the higher-order aberrations, including coma and spherical aberrations, were lower than preoperative levels, according to Nidek.