The FDA has granted issued a Complete Response Letter to Motif Bio regarding the New Drug Approval for iclaprim.
The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Motif Bio for iclaprim. The FDA's decision to not approve iclaprim for the treatment of acute bacterial skin and skin structure infections (ABSSI) was based on the need for additional data, according to the letter.
Iclaprim has a targeted Gram-positive spectrum of activity, which can decrease the use of broad-spectrum antibiotics to avoid resistance build-up, and reduce the impact on the microbiome. According to the FDA, more data is needed to evaluate the risk for liver toxicity before the approval of the New Drug Application.
According to an announcement by Motif Bio, the company will request a meeting with the FDA to determine a possible course of action to address the FDA's concerns.
"We are disappointed for patients and providers seeking an alternative antibiotic to treat ABSSSI. We intend to request a meeting with the FDA, which typically should occur within approximately 30-45 days, to discuss the CRL. We look forward to working with the Agency to discuss options to advance iclaprim towards approval," Graham Lumsden, chief executive officer of Motif Bio, said in a statement.
Iclaprim was evaluated in 2 phase 3 studies, REVIVE-1 and REVIVE-2 clinical trials which 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.
In the REVIVE-1 and REVIVE-2 trials, iclaprim achieved the primary endpoint of non-inferiority (10% margin) when compared to vancomycin 48 to 72 hours after the start of administration of the study drug, in the intent-to-treat patient population.
In the pooled analysis, iclaprim was found to be well tolerated with most adverse events categorized as mild or moderate. According to the company, no patients in the iclaprim group had clinically significant creatinine increases compared to 7 cases reported in the vancomycin group.
“Iclaprim is an antibiotic from an underutilized mechanism of action (trimethoprim is the only US Food and Drug Administration (FDA)-approved dihydrofolate reductase inhibitor); is rapidly bactericidal against nonsusceptible Methicillin-resistant Staphylococcus aureus (MRSA) isolates/strains to vancomycin, linezolid, and daptomycin; suppresses bacterial exotoxin production; and is not nephrotoxic and thus does not require renal dose adjustment,” David Huang, MD, PhD, chief medical officer of Motif Bio said in a previous interview with Contagion®.
Iclaprim was granted Qualified Infectious Disease Product (QIDP) designation and fast track status for the treatment of ABSSSI. Under the Generating Antibiotic Incentives Now Act, if the drug is approved will be eligible for 10 years of market exclusivity in the United States from the date of first approval.