Exebacase's phase II missed its primary endpoint, but a patient subset had a statistically significant response, prompting the FDA meeting and an agreement on the key design features that include a day 14 primary efficacy endpoint for methicillin-resistant S. aureus (MRSA) bacteremia, including right-sided endocarditis. Roger Pomerantz, Contrafect's president, CEO and chairman, said positive results from the upcoming trial, dubbed DISRUPT, could support a BLA. He wasn't alone on that point.
"A superiority design differentiates DISRUPT from other antibiotic studies and the FDA agreed to a BLA filing on positive superiority data," Piper Jaffray analysts wrote Wednesday. "We presently anticipate data in 2021 and FDA approval in 2022."
Pomerantz said positive results from the trial would be history-making, as the first successful treatment post-World War II was vancomycin in 1958. The only advance since then was daptomycin in 2006, a drug that he said was not superior to vancomycin.
"Vanco captures less than 20% of the market because of that," Pomerantz said in Wednesday morning's conference call, adding that MRSA bacteremia is "not rare, but it is neglected."
The phase II's home run for MRSA bacteremia, Pomerantz said, was the clinical responder rate at day 14 in patients treated with exebacase, which was 43% higher than the clinical responder rate in patients treated with standard-of-care antibiotics alone (74% for patients treated with exebacase compared to 31% for patients treated with SOC antibiotics alone, p=0.010).
There is also money to be saved. The phase II data showed the median number of hospital days from study drug administration through discharge was six days in the exebacase-treated group vs. 10 in the standard-of-care group. The 30-day hospital readmission rates among MRSA patients discharged from the hospital were also lower among exebacase-treated patients.
Exebacase's phase III trial will be a single, randomized, double-blind, placebo-controlled study conducted in the U.S. to assess the efficacy and safety of exebacase in approximately 350 patients, an increase over the 121 participants enrolled in the phase II. The phase II had a different patient setting as it was conducted in the U.S., Europe, Latin America, Russia and Israel, with 79.3% of patients enrolled in the U.S. Keeping the trial in the U.S., Pomerantz said, takes away the "confounding, corrupting" variable of standard of care that is found around the world.
Patients entering the phase III study will be randomized 2-to-1 to either exebacase or placebo, with all patients receiving standard-of-care antibiotics. Secondary endpoints include clinical response at day 14 in the all-Staph aureus bacteremia patient group (MRSA and methicillin-sensitive S. aureus), 30-day all-cause mortality in MRSA patients, and clinical response at later timepoints. The phase III will exclude left-sided endocarditis patients "because it has become much more of a surgical disease and should most likely be studied in smaller trial with just left-sided patients," Pomerantz said in the call.
The interim futility analysis will be conducted at about 60% enrollment of the study population. Pomerantz did not want to predict when the top-line data would be available.
Exebacase, licensed from The Rockefeller University, is a recombinantly produced lysin (cell wall hydrolase enzyme) with bactericidal activity against S. aureus. By targeting a conserved region of the cell wall that is vital to bacteria, resistance is less likely to develop to exebacase.
Shares of Contrafect (NASDAQ:CFRX) closed at 36 cents Wednesday.