West Coast Editor

Halozyme Therapeutics Inc. met its goal of filing a new drug application for Enhanze SC, a recombinant human hyaluronidase designed to improve delivery of local anesthesia and contrast agents, as well as for subcutaneous fluid replacement.

The NDA may have come just under the wire to meet the first-quarter deadline, but it has moved with dispatch since the DNA vector that produces the protein was made just 21 months ago.

Getting from vector to NDA is "normally a process that takes many years," noted Jonathan Lim, CEO of San Diego-based Halozyme.

The "spreading agent" Enhanze SC is the first product in Halozyme's Enhanze Technology portfolio, and is being developed for subcutaneous diffusion of anesthesia in ophthalmic surgery, as well as other indications.

Based on combining hyaluronidase with other drugs for improved effects, the technology has yielded other compounds in preclinical work.

"We've tested some monoclonal antibodies as well as some cytokines" subcutaneously, Lim told BioWorld Today. Bioavailability when combined with hyaluronidase in rat models has reached 100 percent, compared to 50 percent or 60 percent with the drugs alone.

"Statistically, it's identical with [intravenous administration]," he said. "It potentially allows patients to do self-injectables rather than having to go into the hospital."

Enhanze SC, billed as likely the first and only synthetic alternative to the slaughterhouse-derived hyaluronidase used today, boasts more than 100 times higher purity than the active ingredient in Wydase, the discontinued bovine enzyme from Madison, N.J.-based Wyeth previously used for anesthesia diffusion enhancement.

"The FDA knows a lot about the enzyme product," which was withdrawn from the market in 2001, and that's helping Halozyme pursue a "very efficient regulatory path" for its replacement, Lim said.

"We should be able to roll it out to all the same markets," which have an incremental value around $300 million, including $50 million domestically for ophthalmology. Specifically, Halozyme's hyaluronidase (rHuPH20) is being investigated for its ability to break down hyaluronic acid, the space-filling gel-like substance in body tissues. Injected into skin or muscle, hyaluronidase can temporarily digest the gel, thus enhancing penetration and diffusion of other injected drugs or fluids.

The company signed a marketing deal with Deerfield, Ill.-based Baxter Healthcare Corp. for Enhanze SC in August, giving Baxter exclusive rights to market, distribute and sell the product in the U.S. and Puerto Rico under a 50-50 profit-sharing arrangement. (See BioWorld Today, Aug. 17, 2004.)

Halozyme's most advanced product is the medical device product Cumulase for infertility. In September, Halozyme submitted a 510 (k) filing. The firm also has a biologic known as Chemophase for oncology indications.

"We're marching toward an [investigational new drug application] filing in the second quarter of this year, getting into the clinic in the second half of the year," Lim said.

Last year, Halozyme raised $13.9 million in a private placement of common stock and warrants with institutional and accredited investors in the largest financing the firm ever conducted. The money was said to be enough to execute the firm's business plan well into 2006. (See BioWorld Today, Oct. 14, 2004.)

The firm issued about 7.9 million shares of common stock at $1.75 per share in the private placement, providing warrants to buy up to 2.4 million more at $2.25 each, with New York-based SG Cowen & Co. LLC serving as placement agent.

Halozyme's stock (AMEX:HTI) gained 10 cents Monday to close at $1.70.