Washington Editor

With a new drug application still under review for Vitrase in vitreous hemorrhage, ISTA Pharmaceuticals Inc. is asking the FDA to approve the drug as a spreading agent to facilitate the dispersion and absorption of other drugs.

The company on Tuesday said it filed a new drug application for the spreading indication, considered an unmet medical need by the FDA. Additional clinical trials were not necessary for the submission.

Under expedited review, ISTA officials hope the application will be approved by the end of the year.

Vitrase, a formulation of purified ovine hyaluronidase, is familiar to the agency as a candidate for single injection to the eye for vitreous hemorrhage. The FDA issued an approvable letter for the indication in April, seeking additional analysis of the existing data and possibly an additional confirmatory study. ISTA and the agency remain in discussions about the next steps in clearing it for approval in vitreous hemorrhage. (See BioWorld Today, April 8, 2003.)

The Dermatologic and Ophthalmic Drugs Advisory Committee in March voted 7-5 saying Vitrase's benefits outweigh its risks when used for vitreous hemorrhage. However, in an 8-4 vote, the panel said ISTA's data didn't support efficacy in that indication. (See BioWorld Today, March 18, 2003.)

Also, if approved as a spreading agent, Vicente Anido, president and CEO of Irvine, Calif.-based ISTA, said the company is asking the FDA to allow it to provide directions for reconstitution of Vitrase for potential treatment applications to the back of the eye, i.e., the first indication. In that case, physicians could use it off label for vitreous hemorrhage, regardless of the FDA's decision.

Meanwhile, ISTA has answered the agency's call about considering Vitrase as a spreading agent. Since 2001, the FDA's drug shortage list has included spreading agents.

Anido told BioWorld Today a spreading agent could be used, for example, in cataract surgery when anesthetics are injected around the eye. In that scenario, a spreading agent would diffuse the anesthesia, allowing the surgeon to reduce the dose.

What's more, Anido and the ISTA team believe Vitrase could be used with other products like cancer medications or radiopharmaceuticals.

Before 2001, a bovine-derived, thimerosal-preserved form of hyaluronidase was used as a spreading agent with other drugs in more than 750,000 ophthalmic surgeries. That particular product was pulled from the market, most likely because it wasn't a big moneymaker.

Anido believes the U.S. market for the bovine-derived version was about $20 million annually. However, he's not sure to what extent the earlier version was marketed.

Specially, the proposed label for Vitrase reads: "Hyaluronidase is a spreading or diffusing substance, which modifies the permeability of connective tissue through the hydrolysis of hyaluronic acid, a polysaccharide found in the intercellular ground substance of connective tissue and of certain specialized tissues, such as the umbilical cord and vitreous humor. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and promotes diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption."

ISTA's stock (NASDAQ:ISTA) fell 4 cents Tuesday to close at $7.11.