LONDON—Motif Bio plc, a clinical-stage biopharmaceutical company specializing in developing novel antibiotics, has announced that iclaprim data are being presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)/American Society for Microbiology (ASM) Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance being held in Lisbon, Portugal, September 4-7, 2018.
The Safety of Iclaprim among Diabetic Patients for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Pooled REVIVE Studies
A post-hoc analysis was conducted on the pooled data from the REVIVE-1 and REVIVE-2 trials to evaluate the safety of iclaprim compared to vancomycin, the current standard of care, in treating ABSSSI patients with diabetes. Eleven percent (127/1198) of the REVIVE intent-to-treat (ITT) population had diabetes, and renal impairment was common among these patients, 39.2% (22/56) in the iclaprim group and 36.6% (26/71) in the vancomycin group.
Overall adverse events in diabetic patients treated with iclaprim (48.2%) were lower compared to vancomycin (52.9%) and there were fewer treatment-related adverse events (AEs) – iclaprim (8.9%) versus vancomycin (15.7%). No patients with diabetes who were treated with iclaprim developed acute kidney injury/increased blood creatinine levels, compared to three diabetic patients in the vancomycin arm. Discontinuation of study drug due to an AE was reported in 3.6% (2/56) of patients with diabetes treated with iclaprim versus 10.0% (7/70) treated with vancomycin.
“Diabetes is a risk factor for ABSSSI and for vancomycin-associated acute kidney injury. Patients with diabetes have worse outcomes with increased clinical failures and longer hospitalizations than patients who do not have diabetes,” said Thomas L. Holland, M.D., MSc-GH, Assistant Professor of Medicine, Duke University School of Medicine. “In the pooled REVIVE ITT population, about 11% of patients had diabetes, and more than a third of those with diabetes had renal impairment. These patients may be particularly vulnerable to vancomycin-related side effects, including kidney toxicity. If approved, iclaprim may be an important new option to treat this patient group.”
Data evaluating the activity of iclaprim in a variety of bacteria, including drug-susceptible versus drug-resistant strains were also presented at the conference. This included:
Iclaprim Activity Against Clinical Isolates Causing Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Phase 3 REVIVE-1 and REVIVE-2 Studies
An evaluation of the activity of iclaprim against clinical isolates causing ABSSSI in the REVIVE trials, demonstrating that iclaprim had potent in vitro activity against S. aureus, including MRSA.
Surveillance of Iclaprim Activity: In Vitro Susceptibility of Drug-Susceptible and Resistant Beta-hemolytic Streptococci Collected During 2012-2016 from Skin and Skin Structure Infections
An evaluation of iclaprim against both drug-susceptible and drug-resistant strains of S. pyogenes and S. agalactiae (samples from patients with ABSSSI collected worldwide during 2012-2016). Data showing iclaprim’s activity had previously been from samples collected prior to 2006. Iclaprim was shown to be active in vitro against these newer strains.
Surveillance of Iclaprim Activity: In Vitro Susceptibility of Gram-Positive Skin and Skin Structure Pathogens Collected During 2004-2016
An evaluation of iclaprim against Gram-positive clinical isolates, including S. aureus (MSSA and MRSA) and beta-hemolytic streptococci collected from patients with ABSSSI between 2004 and 2016. Iclaprim had consistent in vitro activity against these isolates and was shown to be more potent than trimethoprim alone and equally potent compared to trimethoprim-sulfamethoxazole. Iclaprim also had greater potency than standard of care Gram-positive antibiotics such as vancomycin, linezolid and daptomycin against MRSA.
David Huang, MD, Chief Medical Officer of Motif Bio, will also be giving a presentation on iclaprim as part of the State of the Art Lecture: New Antibacterial Agents. In his presentation, Huang will provide an overview of iclaprim data in ABSSSI. A New Drug Application for iclaprim in the treatment of ABSSSI is currently under review at the U.S. Food and Drug Administration with a target action date under the Prescription Drug User Fee Act of February 13, 2019.
“Given the worldwide crisis in antibiotic resistance, there remains a major need for new antibiotic treatments. We have shown comprehensive data indicating that iclaprim has potent activity against a wide variety of Gram-positive bacteria, including MRSA, that cause severe skin infections,” noted Huang. “With its targeted Gram-positive spectrum of activity, low propensity for resistance development, favorable tolerability profile and efficacy results, we think that, if approved, iclaprim could be an important new treatment option for patients with ABSSSI, Including patients with co-morbidities such as diabetes, renal impairment and obesity.”
The posters and presentation will be available in the Development Programs – Publications section of Motif Bio’s website.