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|Motif Bio REVIVE-1 Phase 3 Study Results with Iclaprim Published in Peer-reviewed Journal, Clinical Infectious Diseases|
In the intent-to-treat (ITT) patient population, 80.9% of patients treated with iclaprim and 81% of patients treated with vancomycin achieved the primary endpoint of early clinical response (ECR), defined as a greater than or equal to 20% reduction in lesion size compared with baseline, at the early time point (ETP), 48 to 72 hours after the start of administration of the study drug. Non-inferiority (NI) (10% margin) thus was confirmed for iclaprim compared to vancomycin. Secondary analyses in the study included response to treatment at end of therapy (EOT), at test of cure (TOC), 7-14 days after the last dose of study drug, and safety and tolerability.
The ITT study population included 598 randomized patients from clinical trial sites in the U.S.,
80% (16/20) of diabetic patients in the iclaprim group and 74% (26/35) of diabetic patients treated with vancomycin achieved ECR at ETP. 83% (5/6) of iclaprim-treated patients with moderate/severe renal impairment and 75% (9/12) of vancomycin-treated patients with moderate/severe renal impairment achieved ECR at ETP.
Iclaprim was well tolerated in the study. Treatment emergent adverse events (TEAEs) were generally mild, including headache (10.2% and 2.4%), nausea (9.9% and 5.7%), and fatigue (6.1% and 3.0%), reported in patients in the iclaprim group compared to the vancomycin group, respectively. TEAEs leading to discontinuation were 2.7% and 4.4% in patients in the iclaprim and vancomycin group, respectively. There were no study-drug related TEAEs related to nephrotoxicity in patients treated with iclaprim compared to three reported cases of acute kidney injury in patients treated with vancomycin.
No significant differences were seen between treatment groups in mean values or mean changes in other routine serum laboratory parameters, urinalysis results, vital signs or physical examinations during treatment.
William O’Riordan, MD, FACEP, Chief Medical Officer, eStudySite and principal investigator of the REVIVE-1 study, said: "ABSSSI is a serious infection for which patients are frequently hospitalised for several days. Many of these patients have co-morbidities, such as renal impairment and diabetes. For these patients in particular, there is an urgent need for safer, more effective treatment options. Iclaprim demonstrated strong efficacy and safety results, including no kidney toxicity, in REVIVE-1, the first of two positive Phase 3 trials in ABSSSI. With this profile and its fixed dosing, iclaprim, if approved, could be an important new treatment option for these very sick patients.”
Iclaprim has been designated as a Qualified Infectious Disease Product (QIDP) by the
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Notes to Editors
About Acute Bacterial Skin and Skin Structure Infections
Acute bacterial skin and skin structure infections (ABSSSI) are one of the most common bacterial infections. ABSSSI are potentially serious infections that may require hospitalisation, intravenous antibiotics and/or surgical intervention and 3.6 million patients are hospitalised annually in the U.S. for ABSSSI. An ABSSSI is defined as a bacterial infection of the skin with a lesion size area of at least 75 cm2 and includes cellulitis/erysipelas, wound infections, and major cutanenous abscesses. Approximately 85% of ABSSSI are caused by Gram-positive bacteria, usually Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and Streptococcus pyogenes.
Iclaprim is a novel investigational antibiotic that has a different and underutilised mechanism of action compared to other antibiotics. Iclaprim exhibits potent in vitro activity against Gram-positive clinical isolates of many genera of staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). Iclaprim is rapidly bactericidal, achieving 99.9% in vitro kill against MRSA within 4 to 6 hours of drug exposure versus 8 to 10 hours for vancomycin. To date, iclaprim has been studied in over 1,300 patients and healthy volunteers. In clinical studies iclaprim has been administered intravenously at a fixed dose with no dosage adjustment required in patients with renal impairment or in obese patients. 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.
About Motif Bio
Iclaprim has an underutilised mechanism of action compared to other antibiotics. Clinical and microbiology data indicate iclaprim has a targeted Gram-positive spectrum of activity, low propensity for resistance development, fixed dose administration and favourable tolerability profile. Additionally, data support that the inactive metabolites of iclaprim clear through the kidneys. The Company also plans to develop iclaprim for hospital acquired bacterial pneumonia (HABP), including ventilator associated bacterial pneumonia (VABP), as there is a high unmet need for new therapies in this indication. A Phase 2 trial was conducted to study iclaprim in patients with HABP. Iclaprim has been studied in an animal model of pulmonary MRSA infection which mimics the pathophysiology observed in patients with cystic fibrosis. Iclaprim has been granted orphan drug designation by the U.S.
Iclaprim has received Qualified Infectious Disease Product (QIDP) designation from the
This press release contains forward-looking statements. Words such as “expect,” “believe,” “intend,” “plan,” “continue,” “may,” “will,” “anticipate,” and similar expressions are intended to identify forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause Motif Bio’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.
1 Huang DB, O’Riordan W, Overcash JS, Heller B, Amin F, File TM Jr, Wilcox MH, Torres A, Dryden M, Holland TL, McLeroth P, Shukla R, and Corey GR. A Phase 3, Randomized, double-blind, multicenter study to EValuate the safety and efficacy of intravenous Iclaprim versus Vancomycin for the treatment of acute bacterial skin and skin structure infections suspected or confirmed to be due to Gram-positive pathogens: REVIVE-1. Clinical Infectious Diseases 2017. In Press.