Data from Pharmawand - Curated by EPG Health - Date added 12 June 2018
Motif Bio plc has announced that the pooled efficacy and safety data from its two Phase III trials (REVIVE-1 and REVIVE-2) in patients with acute bacterial skin and skin structure infections (ABSSSI) treated with its investigational drug candidate iclaprim were presented at the American Society of Microbiology (ASM) Microbe 2018 meeting in Atlanta, GA (An Analysis of Pooled Efficacy Data from Two Phase III Trials of Iclaprim Compared to Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections, #640 and A Pooled Analysis of Two Phase III, Randomized, Double-Blind, Multicenter Studies to Evaluate the Safety of Intravenous Iclaprim versus Vancomycin, #641).
The pooled data demonstrate that iclaprim was non-inferior to standard-of-care vancomycin and was well tolerated in this patient population. The posters are available on the Motif Bio website here. The pooled data have also been published in the peer-reviewed scientific journal, International Journal of Antimicrobial Agents (https://doi.org/10.1016/j.ijantimicag.2018.05.012).Both the REVIVE-1 and REVIVE-2 studies were global Phase III trials evaluating iclaprim in patients with ABSSSI. As previously reported, both studies met their primary endpoints of non-inferiority (NI) (10% margin) compared to vancomycin, the current standard of care, at the early timepoint (ETP), 48 to 72 hours after the start of administration of the study drug, in the intent-to-treat (ITT) patient population. The pooled data set included over 1,190 patients. Iclaprim was well tolerated in the two Phase III studies compared to vancomycin. In most patients, adverse events were mild to moderate, with severe adverse events reported in less than 5% of all patients in the pooled data set.
The most frequent adverse reactions in both iclaprim and vancomycin-treated patients were headache and nausea. No deaths occurred among patients treated with iclaprim, while three deaths occurred in the vancomycin group. Acute kidney injury or elevated serum creatinine was reported in seven patients treated with vancomycin, which is known to be nephrotoxic. In contrast, none of the patients treated with iclaprim experienced acute kidney injury or elevated serum creatinine.
The iclaprim fixed dose may, if approved, help reduce the resources required in hospitals since dosage adjustment by health care professionals is avoided and overall hospital treatment costs may be lower, especially in patients with renal impairment. Many standard of care Gram-positive antibiotics are not suitable for hospitalized ABSSSI patients with renal impairment due to efficacy and/or safety issues.
Comment: Iclaprim has a different and underutilised mechanism of action compared to most other antibiotics. Following positive results from two Phase III trials (REVIVE-1 and REVIVE-2), a rolling submission of a New Drug Application (NDA) with the FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSI) has been initiated and is expected to be completed in the second quarter of 2018.