Motif Bio PLC Positive Results for Iclaprim, in the REVIVE-1 Phase 3 Study

Motif Bio plc (LON:MTFB), the clinical stage biopharmaceutical company specialising in developing novel antibiotics, have announced today positive topline results from REVIVE-1, a global Phase 3 clinical trial of its investigational drug candidate iclaprim in patients with acute bacterial skin and skin structure infections (ABSSSI).

Iclaprim achieved the primary endpoint of non-inferiority (NI) (10% margin) compared to vancomycin at the early time point (ETP), 48 to 72 hours after the start of administration of the study drug, in the intent-to-treat (ITT) patient population. Iclaprim also achieved NI (10% margin) at the test of cure (TOC) endpoint, 7 to 14 days after study drug discontinuation, in the ITT patient population.

Keypoints:

• Iclaprim met the primary endpoint
• Iclaprim was well tolerated in the study
• Data from the second Phase 3 ABSSSI Trial, REVIVE-2, expected in the second half of 2017
• NDA submission expected in the first half of 2018

In an analysis of a pre-specified secondary endpoint, 60.4% of patients receiving iclaprim demonstrated resolution or near resolution at end of therapy (EOT), compared to 58.3% of patients receiving vancomycin (treatment difference: 2.07%, 95% CI: -5.80% to 9.94%). In another pre-specified secondary endpoint analysis, using a modified clinical cure TOC endpoint defined by a >90% reduction in lesion size at TOC, no increase in lesion size since ETP and no requirement for additional antibiotics, clinical cure was seen in 68.5% of patients receiving iclaprim and 73.0% of patients receiving vancomycin (treatment difference: -4.54%, 95% CI: -11.83% to 2.74%).

Graham Lumsden, Chief Executive Officer of Motif Bio commented: “The successful completion of REVIVE-1 is a significant achievement for Motif Bio. I would like to thank the patients and physicians that participated in this important study. 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. 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. It is estimated that up to 26% of the 3.6 million ABSSSI patients hospitalised annually in the U.S. have kidney disease.”

William D. O’Riordan M.D., FACEP, Chief Medical Officer, eStudySite commented: “Following the positive outcome in this clinical trial, the differentiated mechanism, potency, spectrum, safety and efficacy of iclaprim, if approved, could provide a valuable new antibiotic treatment option that is urgently needed to offset the rising problem of bacterial resistance.”

Data from REVIVE-2, the second Phase 3 trial, which uses an identical protocol to REVIVE-1 but has different trial centres, are expected in the second half of 2017 and submission of a New Drug Application (NDA) for iclaprim for the treatment of ABSSSI is anticipated in the first half of 2018.

Iclaprim has been designated as a Qualified Infectious Disease Product (QIDP) by the U.S. Food and Drug Administration (FDA) for the treatment of ABSSSI and hospital acquired bacterial pneumonia (HABP), which enables Priority Review following submission of a NDA. If approved, it is anticipated that iclaprim will be eligible to receive 10 years of market exclusivity in the U.S. from the date of approval. The FDA has also granted Fast Track designation for iclaprim.

REVIVE-1 Overview and Adverse Event (AE) Summary

REVIVE-1 is a 600-patient double-blinded, active-controlled, global, multicentre trial, in patients with ABSSSI that compares the safety and efficacy of an 80mg intravenous dose of iclaprim with a 15mg/kg intravenous dose of vancomycin. Treatments were administered every 12 hours for 5 to 14 days.

Iclaprim was well tolerated in the study, with most adverse events categorized as mild.

Motif Bio plans to present the full data from this study at an upcoming scientific forum.

Zeus Capital said:

Motif Bio Plc, a late clinical stage antibiotic development company, announced positive results this morning in the first of its two iclaprim phase III clinical trials, REVIVE-1, comparing iclaprim to vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSI). Iclaprim, a next-generation antibiotic targeting an under-utilised mechanism of action which causes rapid killing of bacteria, is being developed for the treatment of serious and life threatening bacterial infections. On the key primary endpoint in the study, early clinical response at 48-72 hours after drug treatment began, 80.9% of patients on iclaprim achieved a positive response compared to 81.0% of patients on vancomycin, well within the 10% non-inferiority margin required by the FDA. Iclaprim was also shown to be safe and well-tolerated compared to vancomycin. With these positive results from REVIVE-1 we have increased the probability of success for the iclaprim development program from 65% to 75% raising our risk-adjusted NPV for Motif Bio to almost £240m or 122p per share (previously £210m and 107p per share).

Primary endpoints met – A total of 598 patients were enrolled into Revive-1 and randomised 1:1 (the intent-to-treat population: iclaprim N=298, vancomycin N=300). Iclaprim was successfully demonstrated to be equally as effective as vancomycin in the treatment of ABSSSI as measured against the primary endpoint criteria of Early Clinical Response (ECR; defined as ≥20% reduction of lesion area at 48-72 hours after treatment start) with 241 of 298 iclaprim-treated patients (80.9%) achieving ECR compared to 243 of 300 (81.0%) in the vancomycin group. Similarly, against the later time point assessing the clinical cure (test-of-cure, TOC, at 7-14 days after study drug discontinuation) 84.2% (251/298) and 87.0% (261/300) achieved a positive outcome in the iclaprim and vancomycin arms, respectively. Importantly, for both endpoints, iclaprim was demonstrated to be within the pre-defined 10% margin of non-inferiority.

Other clinical measures – iclaprim was also shown to be efficacious according to other measures of clinical response including 2 pre-specified efficacy endpoints: resolution or near resolution at the end of therapy (iclaprim 60.4% vs vancomycin 58.3%), and modified clinical cure (iclaprim 68.5% vs vancomycin 73.0%). Iclaprim was shown to be safe and well-tolerated with drug-related adverse events (AEs) occurring in 19.5% of iclaprim-treated patients compared to 17.8% of vancomycin-treated patients. AEs leading to discontinuation of the study drug occurred in 2.7% of iclaprim-treated patients and 4.4% of vancomycin-treated patients. One death occurred in the study (in the vancomycin-treated group of patients).