Motif Bio has initiated a NDA rolling submission for iclaprim, a Gram-positive-targeted investigational antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in high-risk MRSA (Methicillin-resistant S. aureus) patients.
In the US, 3.6 million patients of this population are hospitalised annually. Motif Bio said the antibiotic may be suitable for first-line empiric therapy in ABSSSI patients, especially those with renal impairment, with or without diabetes. Unlike many standard of care antibiotics, iclaprim is only minimally cleared via the kidneys. No nephrotoxicity was observed with iclaprim in the REVIVE Phase 3 trials and dosage adjustment has not been required in patients with renal impairment.
Motif Bio plc said it expects the NDA submission to complete until June 2018 latest. Iclaprim has received Qualified Infectious Disease Product (QIDP) designation from the FDA together with Fast Track Designation. Motif Bio hopes to receive NDA approval for iclaprim as a new chemical entity with QIDP designation as it will be eligible for 10 years of market exclusivity in the U.S. starting from the date of first approval.
According to Motif Bio, iclaprim has an underutilised mechanism of action compared to other antibiotics. The diaminopyrimidine dihydrofolate reductase blocker, was licenced in 2001 from Roche by its spin-out company Arpida, which later merged with Evolva. Arpida ran two Phase III clinical trials for complicated skin and skin structure infections, called ASSIST 1 and 2, that were completed by 2008 but as of 2017 had not been published in the medical literature.
A NDA was filed with the FDA based on these trials and was rejected due to failure to show non-inferiority and due to safety concerns, especially drug-induced QT prolongation. The FDA advisory committee said that the drug "should not be developed further" based on the results presented. A parallel application for marketing approval to the EMA was withdrawn in 2009; in the announcement of the withdrawal, the EMA said that there was insufficient data from clinical studies to justify the dosage proposed by the company and that resistance to the drug had already been seen in the clinical trial data.
Arpida sold off iclaprim to Acino Pharma in November 2009 and the company handed over the rights to to a group called Life Sciences Management Group, Inc., which assigned its rigths to Nuprim. In 2015 Motif BioSciences Inc. and Nuprim merged. In 2017, Motif Bio announced positive results with iclaprim in two Phase III trials (called REVIVE 1 and 2) to show non-inferiority to vancomycin in acute skin and skin structure infection. In September 2017 the FDA granted orphan drug status to iclaprim for the treatment of Staphylococcus aureus lung infections in people with cystic fibrosis.