National Editor

Having won the go-ahead from the FDA for Phase III trials with its cancer drug, Taxoprexin, Protarga Inc. said it would start enrolling patients in the first pivotal study in December, testing the drug in metastatic melanoma.

The agency gave its OK for Phase III trials in pancreatic cancer, too, and that study is expected to begin next year, if Protarga has enough cash.

As of Thursday, "we've pulled our [initial public offering] and we're free to do a private placement," said Nigel Webb, chairman, president and CEO of Protarga, based in King of Prussia, Pa. The IPO was filed late last year. (See BioWorld Today, Dec. 13, 2001.)

"We need to raise some more money," he said. "We just started doing that right now, and in this market I'm not good at speculating at what will happen."

What's practically certain to happen, though, is the start of the melanoma study. All of the necessary Taxoprexin has been manufactured and the protocol has been finalized, Webb said.

The drug, a member of the taxane class of drugs, is made by linking the fatty acid docosahexaenoic acid to the widely used anticancer agent paclitaxel. Such a link is intended to delay the release of the agent until the target tissue takes up the drug, and is the basis of what Protarga calls its Targaceutical platform.

In metastatic melanoma, the Phase III study will enroll about 560 patients in the U.S., Europe and Australia, and will test Taxoprexin as a first-line treatment, comparing survival of patients who get the drug by infusion every three weeks with those given decarbazine, the current treatment for melanoma, also intravenously infused.

The company has encouraging Phase II data from about 300 cancer patients who showed a safety profile for the drug that includes fewer of the troubling side effects of chemotherapy.

Webb said the company has been conducting "experimental medicine on a grand scale," with eight Phase II trials that are finished or nearly done in eight types of cancer.

"The FDA wants to see everything all the time, so we sent in all the interim data on all the studies," he said. "We want to be a little bit careful, but overall we can say the drug has a different activity profile relative to the other taxanes."

Those well-known taxanes are New York-based Bristol-Myers Squibb Inc.'s Taxol (paclitaxel) - of which IVAX Corp., of Miami, has a generic version called Taxene - and Frankfurt, Germany-based Aventis SA's Taxotere (docetaxel).

More details will be offered at an investors' conference next week, but Webb offered BioWorld Today a preview of the results with Taxoprexin compared to other taxanes.

"The neuropathy rate [with Taxoprexin] is down around 20 percent, and that compares to 50 [percent] to 60 percent with Taxol and Taxotere," he said, noting that neuropathy is "the most problematic side effect" of such therapies.

"We only see mucositis in 0.4 percent of patients," he added. The occurrences of that condition (paired with stomatitis on the labels) in Taxol and Taxotere patients are 31 percent and 42 percent, respectively.

"It's a pretty horrible side effect, because you can't swallow," said Webb of mucositis.

Hair loss was vastly improved, too. The condition arises in 4 percent of Taxoprexin patients, compared to 80 percent to 85 percent of patients given the other taxanes, Webb said.

At the same time, Protarga's drug is believed to have the benefits of the other taxanes, which are extracted from the Pacific yew tree, Taxus brevifolia, and which represent the largest class of cancer drugs now.

"They essentially stop cancer cells from dividing, so they're useful as monotherapy," Webb noted. "Many of the new drugs [other than taxanes] only work in combination with other drugs" - and many of the new drugs, such as South San Francisco-based Genentech Inc.'s breast cancer drug Herceptin (trastuzumab), are used in tandem with taxanes.

Although Protarga is pursuing development of Taxoprexin as a monotherapy, Webb noted, the possibility of its use as an adjunct to other drugs boosts its market potential.

Unlike Protarga, he said, other researchers are working on taxanes in a manner that suggests they will seek approval based on safety.

"It's much less controversial go after a survival endpoint," Webb said.

Protarga has synthesized more than 250 Targaceutical compounds so far, and its technology netted the firm its first corporate partnership this summer with ICOS Corp., of Bothell, Wash., to chemically link the fatty acid vectors to ICOS' cancer drug candidates, which are based on cell cycle checkpoints. (See BioWorld Today, July 30, 2002.)