New iclaprim data were presented at the American Society For Microbiology (ASM) Microbe 2019 meeting

Motif Bio plc reported that new iclaprim data were presented at the American Society For Microbiology (ASM) Microbe 2019 meeting held in San Francisco, CA, USA, June 20-24, 2019.David Huang, MD, PhD, Chief Medical Officer of Motif Bio, said:“The posters presented at ASM Microbe include additional data from the Phase III clinical trials with iclaprim in bacterial skin and skin structure infections, notably improvements in efficacy parameters and Cmax ( see below) with the fixed dosing regimen compared to the weight-based dose regimen, and analysis of subpopulations who had co-morbidities such as obesity, diabetes and renal impairment, or were elderly.”

1. Pharmacokinetic analysis shows improvement in efficacy parameters and Cmax with iclaprim fixed dose versus weight-based dose Data presented included an analysis of the pharmacokinetics of the iclaprim fixed dose used in the REVIVE Phase III trials in acute bacterial skin and skin structure infections (ABSSSI) compared to the weight-based dose used in the earlier ASSIST trials with iclaprim for complicated skin and skin structure infections (cSSSI) (Population Pharmacokinetic (PK) Analysis of the Fixed Dose of Iclaprim in the Phase III REVIVE Studies for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)). The analysis showed that two efficacy parameters (AUC/MIC and T>MIC2) were improved with the fixed two-hour 80mg dose by 54% and 67%, respectively. Cmax was improved by 7% with the fixed dose compared to the 30-minute weight-based dose. The fixed dose regimen may help reduce the resources required in hospitals, since dosage adjustment by clinicians is avoided, and overall treatment costs may be lower, especially in patients with obesity or renal impairment.

2. Iclaprim subpopulation analysis shows iclaprim used to treat patients with variety of co-morbidities in Phase III trials Motif Bio also presented an analysis of the patient populations treated with iclaprim in the REVIVE and earlier ASSIST Phase III trials (Iclaprim Use across Various Subpopulations Treated for Bacterial Skin and Skin Structure Infections). Overall, 1,093 patients with ABSSSI/cSSSI were exposed to iclaprim in these studies. Older patients and patients with co-morbidities such as obesity, diabetes, and renal impairment were well represented across the trials. In the REVIVE and ASSIST trials, respectively: 12% and 16% of patients treated with iclaprim were 65 years of age or older; 15% and 8% were obese (body mass index >35 kg/m2); 9% and 12% had diabetes; and 15% and 41% had renal impairment. The median treatment duration was seven days in the REVIVE studies and ten days in the ASSIST trials.

3. Iclaprim is active against various Gram-positive multi-drug resistant bacteria in updated surveillance analysis, including those resistant to other antibiotics. Iclaprim demonstrated potent activity against various Gram-positive multi-drug resistant streptococci that were collected from patients with ABSSSI between 2013 and 2017 in locations around the world (Surveillance of Iclaprim Activity against Multi-Drug Resistant Streptococci Collected from Patients with Skin and Skin Structure Infections from 2013-2017 from Locations Worldwide). This included isolates that had multi-drug resistance to azithromycin, clindamycin and tetracycline. Given the growing public health concern about antibiotic resistance, it is important to continue to monitor the activity of iclaprim against these bacteria.

Cmax: Maximum concentration that a drug achieves in a tested area after the drug has been administrated and prior to the administration of a second dose).

Comment: In February 2019 the company received a Complete Response Letter from the FDA regarding the New Drug Application for iclaprim for the treatment of acute bacterial skin and skin structure infections (ABSSSI).