Avant Immunotherapeutics (Needham, Massachusetts) 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.
The company also said that GlaxoSmithKline (London), its worldwide partner for commercializing the Rotarix rotavirus vaccine, won approval in the European Union for use of the vaccine in preventing gastroenteritis caused by the bug in children.
Avant is due $40 million from GlaxoSmithKline when the drug is launched.
Una Ryan, president and CEO, 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.
The latest TP10 study screened 309 female patients, with 297 patients randomized to get either a 5 mg/kg dose or placebo 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, 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],'" she 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 (Dallas) 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. Lonza Biologics , a unit of Lonza Group Ltd. (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" showing 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 from NitroMed (Lexington, Massachusetts), directed at black patients, won FDA approval last June. The compound is a fixed-dose combination of the generic drugs isosorbide dinitrate and hydralazine.
To many, however, the TP10 news might be more likely to recall last November's word from Alexion Pharmaceuticals (Cheshire, Connecticut), which said its monoclonal antibody fragment aimed at inhibiting complement-mediated tissue damage failed to hit statistical signficance 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.