Launch of the once-rejected antibiotics Orbactiv and Dalvance last year has encouraged newly founded company Motif Bio to resurrect a third antimicrobial agent in iclaprim mesylate. The London-listed group has raised £25m ($39m) to back new pivotal trials of iclaprim in bacterial skin infections, having changed the comparator drug and endpoint after discussions with the FDA.
The original rebuffing of all three agents occurred in a 13-month period late in the last decade, a time in which the US regulator had been shaken by the debacle of Sanofi’s Ketek, over which safety and data integrity questions had emerged after its 2004 launch. “When we saw the approval of Orbactiv and Dalvance, and we thought, there’s confirmation that the FDA has changed,” Motif's chief executive Graham Lumsden tells EP Vantage.
Intervention
As with Allergan’s Dalvance and the Medicines Company’s Orbactiv, it has taken the intervention of the US government to kickstart development, via the creation of the Qualified Infectious Diseases Product (QIDP) programme. Products that receive this designation gain faster review and extra marketing exclusivity.
The latter benefit was essential to the continued development of iclaprim. Originally discovered by Roche, the antibiotic was developed by the Swiss group Arpida until its original rejection by the FDA and European authorities. When Arpida ran into difficulty financing new trials, iclaprim was sold to a second Swiss company, Acino, and Motif acquired it from there.
With the QIDP designation, iclaprim will have five years of exclusivity in addition to the five years usually granted a newly approved product. It has received the designation for hospital-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.
New trial
The group has not yet put a timetable on advancing the agent into phase III skin infection trials, but has selected a clinical research organisation – it has not disclosed the name – that has preparation work underway, including selecting sites and investigators. The target date for submitting the pivotal data to the FDA and European Medicines Agency is the second half of 2017, Mr Lumsden says.
Having met with FDA staff, Motif is planning some variations to the trial design that Arpida conducted. A fixed dose rather than one that varies on patient weight, an efficacy endpoint focusing on skin lesion shrinkage early in therapy rather than efficacy once therapy has ended, and bumping the trial population from 500 to 600 will be among the changes.
The comparator drug will be vancomycin, which was the control in iclaprim’s phase II studies, rather than the linezolid (Zyvox) arm that Arpida had used – at the time, linezolid was thought to offer some benefit over vancomycin.
“They demonstrated non-inferiority to linezolid, but there was debate and discussion around the non-inferiority margins, which resulted in the FDA’s complete response letter,” Mr Lumsden says. “We’re going up against vancomycin because the phase II study looked really good, and it’s the standard of care.”
With Orbactiv and Dalvance having already launched, the question for Motif is whether there is also room for iclaprim. Mr Lumsden notes that it has a different mechanism of action, and as hospitals seek to limit the development of strongly resistant strains the use of cycling drugs in and out of use on a schedule or mixing has become more common.
Building value
A listing on London’s AIM market for growth companies was executed in order to get to a publicly traded status quickly, which was necessary in order to raise the capital to purchase the iclaprim intellectual property. However, a dual listing on Nasdaq is being considered, Mr Lumsden says.
“Our market cap is about £60-61m ($95m). That’s not bad since we just listed in April as a brand new company,” he says. “The closest comparable we have is Paratek Pharmaceuticals. They’re doing almost exactly the same thing we are. Their market capitalisation is about $440m. Partly it’s because they’re on Nasdaq. So we would be crazy not to look at Nasdaq as an obvious next step.”
It is a continuation of a recent trend in pharma – new companies repurposing abandoned projects – with the difference that the argument for dusting off iclaprim is perhaps stronger than projects in Alzheimer’s disease or oncology (Checkmate joins the asset resuscitation game, August 13, 2015).
Reduced regulatory risk and strong late-stage evidence suggest continued work may not be a waste of time and money – and in the case of Dalvance, Durata Therapeutics’ perseverance rewarded its shareholders with a tidy takeout (Takeout of Durata shows antibiotics investment can pay dividends, October 7, 2014). Mr Lumsden and his investors clearly hope this is a distinctive motif of the antibiotic space.
To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @ByJonGardner on Twitter
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