Pooled analyses of 2 phase 3 trials have conclusively established the safety and effectiveness of iclaprim compared to vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSI).
David Huang, MD, PhD
Pooled analyses of 2 phase 3 trials have conclusively established the safety and effectiveness of iclaprim compared to vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSI). The results cap the efforts needed for an approval application to the US Food and Drug Administration which is slated to happen within weeks.
“We have a good antibiotic here,” said David Huang, MD, PhD, Motif BioSciences Inc., Princeton, New Jersey, who presented the tandem posters the 2018 ASM Microbe Meeting and spoke with Contagion®.
The pooled analyses involved the phase 3, randomized, double-blind REVIVE-1 (NCT02600611) and REVIVE-2 (NCT02607618) trials of iclaprim, a diaminopyrimidine, compared to vancomycin for the treatment of patients with ABSSSI.
In the pooled analyses of 593 patients treated with iclaprim and 605 treated with vancomycin, the noninferiority of iclaprim to vancomycin was confirmed during median treatment durations of 7 days for both drugs. Early clinical response was apparent for 79.6% of patients treated with iclaprim and 78.8% treated with vancomycin.
The pooled safety data of 592 patients treated with iclaprim and 599 treated with vancomycin confirmed that iclaprim was well tolerated. Treatment-emergent adverse events were comparable in prevalence to vancomycin (49.2% vs 43.6%) as were serious adverse events (4.2% vs 4.7%). The comparability extended to the types of adverse events, mainly nausea (7.8% vs 5.7%), headache (6.3% vs 6.0%), and cellulitis (4.6% vs 2.3%). The median treatment duration for both iclaprim and vancomycin was 7 days. No deaths occurred in patients treated with iclaprim. The 3 deaths in the vancomycin group were deemed unrelated to the drug. Liver and kidney dysfunctions were rare and comparable. Cardiac disruption evident as QTc prolongation was only evident in 3 patients treated with iclaprim and 1 patients treated with vancomycin.
In REVIVE-1, patients were randomized 1:1 to receive intravenous (IV) iclaprim 80 mg or vancomycin 15 mg/kg. Treatments were administered every 12 hours for 5 to 14 days. Baseline and demographic characteristics were comparable between the 2 groups.
The REVIVE-2 study was a global phase 3 trial evaluating iclaprim in 600 patients with ABSSSI randomized to iclaprim (n = 295) or vancomycin (n = 305). As previously reported by Contagion® and now as published, the study met its primary endpoint of noninferiority to vancomycin, the current standard of care, within 3 days after treatment and for up to 2 weeks.
Iclaprim is a novel investigational antibiotic that is effective against Gram-positive multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, with activity against some Gram-negative bacteria, including Haemophilus influenzae and Moraxella catarrhalis. The antibiotic acts to inhibit the enzyme dihydrofolate reductase. Only 1 other drug, trimethoprim, has the same target.
Motif BioSciences has publicly committed to an FDA submission for approval of iclaprim for ABSSSI in the second quarter of 2018.
Headshot Source: Motif Bio website: motifbio.com/about/management-team/
David Huang, Employee, Motif BioSciences Inc.
An Analysis of Pooled Efficacy Data from Two Phase 3 Trials of Iclaprim Compared to Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Primary Author Block: D. Huang1, E. Desplats2, B. Balser2; 1Motif / Rutgers New Jersey Med. Sch., New York, NY, 2Veristat, Southborough, MA
A Pooled Analysis of Two Phase 3, Randomized, Double-Blind, Multicenter Studies to Evaluate the Safety of Intravenous Iclaprim versus Vancomycin
D. Huang1, E. Desplats2, R. Shukla3, B. Balser2; 1Rutgers New JerseyMed. Sch./Motif BioSci., New York, NY, 2Veristat, Southborough, MA, 3Motif BioSci., New York, NY
Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at email@example.com.