The PDUFA action date has been set for February 13, 2019.
The US Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for Motif Bio’s iclaprim for the treatment of acute bacterial skin and skin structure infections (ABSSSIs).
Iclaprim has a targeted Gram-positive spectrum of activity, and unlike broad-spectrum agents, this approach seeks decrease the use of broad-spectrum antibiotics in order to avoid resistance build-up, and to reduce the impact on the microbiome.
The acceptance of the NDA was based on promising results yielded from 2 phase 3 trials (REVIVE-1 and REVIVE-2), which established the safety and effectiveness of iclaprim compared with vancomycin, the standard of care, for the treatment of patients with ABSSSI.
The pooled analyses of REVIVE-1 and REVIVE-2 included a total of 593 patients who were treated with iclaprim and 605 who were treated vancomycin. In both trials, the drug was administered intravenously at a fixed dose.
The primary endpoint of non-inferiority (10% margin) compared with vancomycin at 48 to 72 hours following administration of the drug in the intent-to-treat population were met in both trials. The drug also achieved noninferiority (10% margin) 7 to 14 days following the discontinuation of the study drug. Additionally, investigators noted an early clinical response in 79.6% of patients treated with iclaprim compared with only 78.8% of those treated with vancomycin.
Pooled safety data of 592 patients who were administered iclaprim and 599 who received vancomycin proved that iclaprim was well-tolerated. Additionally, the number of treatment-associated adverse events for iclaprim were comparable to vancomycin in prevalence (49.2% vs 43.6%), and the same held true for serious adverse events (4.2% vs 4.7%).
In a previous interview with Contagion®, William O’Riordan, MD, FACEP, chief medical officer of eStudySite, discussed the distinguishing features of the drug.
“It has a very unique mechanism of action where, in the future—and we can’t say conclusively, but it will look very difficult because of its 2 mechanisms—for resistance to occur. I think that is a unique feature of this antibiotic,” he explained. “It interferes with dihydrofolate reductase, which is intimately involved with the bacterial cell and the cell integrity and does away with the cell itself.”
The iclaprim fixed dose could potentially help reduce the number of resources required to treat a patient and reduce costs for treatment of patients, especially those with renal impairment,
according to Motif Bio.
There are also plans to develop iclaprim for hospital-acquired pneumonia including ventilator-associated bacterial pneumonia due to a high unmet need for new treatments. Favorable results have already been reported from a phase 2 trial assessing the use of iclaprim in HABP patients and, as such, a phase 3 trial is currently being planned.
Previously, iclaprim has also been granted an orphan drug designation by the FDA for the treatment of Staphylococcus aureus lung infections in patients with cystic fibrosis.
Iclaprim has also received Qualified Infectious Disease Product (QIDP) designation and fast track status for the treatment of ABSSSI. Under the Generating Antibiotic Incentives Now Act, if iclaprim is approved as a New Chemical Entity, the drug will be eligible for 10 years of market exclusivity in the United States from the date of first approval.
The FDA has set a target decision date under the Prescription Drug User Fee Act (PDUFA) of February 13, 2019.