Motif Bio antibiotic hits endpoint in skin infection phase 3

Motif Bio has posted data from a phase 3 trial of its antibiotic candidate iclaprim. The drug held its own against established antibiotic vancomycin, setting Motif Bio on a path it sees leading to a filing for FDA approval in the first half of next year.

Investigators enrolled close to 600 patients with acute bacterial skin and skin structure infections (ABSSSI) in the phase 3 and randomized them to receive either iclaprim or vancomycin. The main goal was to show iclaprim was as good as vancomycin at triggering a 20% reduction in lesion area in the 48 to 72 hours after treatment. And the experimental antibiotic did so, with its 80.9% early clinical response rate coming in a tenth of a percentage point below that achieved by vancomycin.

Iclaprim also performed acceptably against other endpoints. There was little to separate the two treatments in terms of the proportion of patients achieving clinical cures in the 7 to 14 days after stopping taking the drugs. And the regimens delivered comparable rates of resolution at the end of therapy and against a modified clinical cure.

With iclaprim performing no better than vancomycin in terms of efficacy, safety is central to the envisaged commercial positioning of the antibiotic. Motif Bio is yet to provide a detailed look at the safety data. But it said most of the adverse events in the iclaprim arm were mild. The two arms of the trial reported similar rates of drug-related adverse events. Numerically fewer patients in the iclaprim arm experienced events that were either classed as serious or led to the discontinuation of treatment.

Attention now turns to a second phase 3 of iclaprim, which has the same design but is enrolling patients at different sites. If that trial delivers positive data, Motif Bio plans to file an NDA in the first half of next year, teeing it up to finally succeed in bringing iclaprim to market.

“We believe that iclaprim, if approved, could be an important option for patients with ABSSSI, especially for patients with severe infections who may also have kidney disease with or without diabetes,” Motif Bio CEO Graham Lumsden said in a statement. “Unlike current standard of care antibiotics, in clinical trials to date, nephrotoxicity has not been observed with iclaprim and dosage adjustment has not been required in renally impaired patients.”

London-based Motif Bio thinks one-quarter of the 3.6 million ABSSSI patients admitted to U.S. hospitals each year has kidney disease. The size of that opportunity persuaded Motif Bio to pick up iclaprim after Arpida’s attempts to win approval fell flat in 2009.

Following the overwhelming rejection of the filing by its Anti-infective Drugs Advisory Committee, the FDA issued a complete response letter telling Arpida to run another study to show the efficacy of iclaprim. The failure of iclaprim to match the efficacy of Pfizer’s Zyvox—and three deaths possibly linked to the drug—underpinned the setback.

Motif Bio has faced its own travails in trying to get the drug back in front of the FDA. Late last year, the company revealed its liabilities had exceeded its cash, raising doubts about its ability to push the program over the finish line. The near-term threat to the viability of Motif Bio dissipated when it pulled off a Nasdaq IPO and accompanying share offering in Europe.

At the time, Motif Bio said cash from those transactions would see it through to the delivery of data from the first phase 3 trial but that it would need to raise more money to fund the second study to completion.

Shares in Motif Bio opened up 20% in London following the release of the phase 3 results.