West Coast Editor

Avant Immunotherapeutics Inc. said GlaxoSmithKline plc, its worldwide partner for commercializing the Rotarix vaccine, won approval in the European Union for preventing gastroenteritis caused by rotavirus in children, and Avant is due $40 million when the drug is launched.

At the same time, the firm reported another batch of preliminary Phase II data proving that its lead complement inhibitor, TP10, failed to work in females undergoing high-risk cardiopulmonary bypass surgery, and the company said it will focus on males instead - in whom the drug has demonstrated strong Phase II efficacy.

Una Ryan, president and CEO of Needham, Mass.-based Avant, told investors during a conference call that both events are positive, since the confirmatory Phase II outcome allows the firm to "aggressively partner the TP10 program for a males-only indication," whereas earlier data proved less clear.

After a Monday of trading that ranged between $1.84 and $2.19, Avant’s stock (NASDAQ:AVAN) closed at $2.08, up 7 cents.

The latest TP10 study screened 309 female patients, with 297 patients randomized to get either a 5 mg/kg dose (n=150), or placebo (n=147), as a 30-minute intravenous infusion. They were followed for 28 days after surgery. The primary efficacy endpoint of the study was the comparison of TP10-treated patients vs. placebo in the composite incidence of death and myocardial infarction (heart attack).

Although the outcome failed to reach statistical significance in the intent-to-treat population (p=0.2555), TP10 proved well tolerated with no apparent differences in the safety profiles of the treatment groups.

After an earlier Phase II trial yielded an insufficient outcome in women, Avant met with the FDA regarding a possible males-only study, Ryan said, but "at that time, we had a very small number of women, and the result we got could have been a fluke based on insufficient numbers. You have to do these [confirmatory] trials," though investors may lose patience.

"Nobody wanted to wait for all the safety trials that had to be done with Rotarix [either]," Ryan added, but even regulators were not convinced by the first bad findings in women.

"In fact, the FDA said, ‘Don’t give up on females [yet],’" Ryan recalled.

With the most recent Phase II results, the picture has changed. Full data from the trial will be offered at a scientific session, Ryan said, and the November meeting of the American Heart Association is a logical choice, though "we will leave that to the cardiac surgeons who enrolled those patients."

Meanwhile, Avant will be looking for a TP10 partner.

"Clearly, there are [potential] partners who are good at making protein drugs like this," Ryan said, but Lonza Biologics plc, a unit of Lonza Group Ltd., of Basel, Switzerland, is making TP10 now, through a process developed with Avant - which will "very likely continue with Lonza" for that service, especially if the chosen partner lacks manufacturing capability.

Asked by an analyst about the precedent for a gender-specific trial in heart patients, Ryan cited "plenty of evidence" of differences between males and females in clinical response to various drugs, and noted differences found between races, too.

Although she did not cite the example, BiDil, a heart-failure treatment directed at black patients from NitroMed Inc., of Lexington, Mass., won FDA approval in June. The compound is a fixed-dose combination of the generic drugs isosorbide dinitrate and hydralazine (See BioWorld Today, June 27, 2005.)

To many, though, the TP10 news might be more likely to recall last November’s word from Cheshire, Conn.-based Alexion Pharmaceuticals Inc., which said its monoclonal antibody fragment aimed at inhibiting complement-mediated tissue damage failed to hit statistical significance in the Phase III trial’s primary endpoint - nonfatal heart attack or death through 30 days after coronary artery bypass graft surgery, in moderate to high-risk patients. (See BioWorld Today, Nov. 28. 2005.)

Alexion’s report did not distinguish between male and female patients. Still, the failure caused Kate Winkler, senior director of health care and life sciences research for Global Crown Capital LLC in San Francisco, to wonder whether positive male data with Avant’s "similar" TP10 will hold up in further testing.

Winkler, who no longer actively covers Avant, told BioWorld Today that TP10 anyway is a "rather peripheral project, and not the reason to invest in the company. Rotarix royalties and the company’s pipeline of infectious disease vaccines are what excite me."

The European approval for Rotarix triggers a $4 million milestone payment, half of which is creditable against royalties. More importantly, the approval brings Avant closer to the $40 million to be paid by Paul Royalty Fund II LP at the time of launch in Europe.

"We expect to receive this around the middle of the year," Ryan said.

Last May, PRF, of New York, bought for $61 million an interest in the net royalty of Rotarix against rotavirus, an affliction that causes severe diarrhea and vomiting in babies and kills about 600,000 children worldwide each year. (See BioWorld Today, May 19. 2005.)

Under the terms of the deal with PRF, Avant got unconditional payments of $5 million at closing, and another $5 million by Dec. 1, 2005. The launch of Rotarix in the U.S. could bring between $9 million and $11 million in a milestone payment, depending on the date.

Developed at the Cincinnati Children’s Hospital Medical Center, oral Rotarix is the first human rotavirus vaccine derived from a human virus strain available. Filings have been made in more than 75 countries, and Ryan said London-based GSK is expected to file in the U.S. early next year.

At the end of the third quarter, Avant had $22.2 million in cash, supplemented by the December milestone payment from PRF, and Avant ended 2005 with about $23.5 million. The burn rate for this year is estimated at $17 million to $20 million.

"Now is a great time to be a vaccine company," Ryan said, adding that Avant - with three more products due to enter the clinic by the end of this year - is in a "strong financial position to build shareholder value."