Melinta Therapeutics, a privately held company developing novel antibiotics to treat serious bacterial infections, today announced top-line results from the second phase III study (RX-3341-303 NCT01984684) of Baxdela (delafloxacin), an investigational anionic quinolone in development for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI).
Baxdela met the primary endpoints required by the FDA as well as the EMA in this confirmatory pivotal study. Baxdela, with its broad spectrum activity against Gram-positive and Gram-negative bacteria, including MRSA, was tested as an intravenous (IV)-to-oral monotherapy against standard of care, IV-only combination of vancomycin plus aztreonam.
In the intent-to-treat population (ITT), IV-to-oral Baxdela met the FDA’s primary endpoint of statistical non-inferiority (10% non-inferiority margin) at the early clinical response at 48-72 hours after initiation of therapy (83.7%) compared to IV vancomycin combination therapy with aztreonam (80.6%). The 95% confidence interval for the treatment difference had lower and upper bounds of -2.0% and 8.3%, respectively. Baxdela also met the EMA’s required endpoint of statistical non-inferiority (57.7%) compared to vancomycin plus aztreonam (59.7%) based on the investigator’s assessment of complete cure (resolution of all baseline signs and symptoms) at the follow-up visit in the ITT population. Lower and upper bounds of the 95% confidence interval for the treatment difference were -8.6% and 4.6%, respectively. In addition, Baxdela was comparable to vancomycin plus aztreonam in achieving treatment success at Follow-Up (cure or improved, with no further antibiotics needed) with success rate of 87.2% vs 84.8%, respectively. IV/oral Baxdela monotherapy successfully eradicated Gram-positive pathogens, including MRSA, and Gram-negative pathogens at rates comparable to IV vancomycin/aztreonam combination treatment.
Both intravenous (IV) and oral Baxdela were well-tolerated in the study participants.
Overall adverse event rates were similar between treatment arms. The most common treatment-emergent adverse events on Baxdela were diarrhea and nausea, which were generally mild and did not lead to treatment discontinuation. The oral formulation of Baxdela was well tolerated with no increase in GI events compared to the IV formulation. Only 1.2% of Baxdela-treated patients discontinued due to treatment-related adverse events.
In this study, obese patients (BMI= 30kg/m2) constituted 50% of the enrolled population and had a higher prevalence of co-morbidities such as diabetes and cardiovascular disease than non-obese patients. Co-morbidities present challenges to appropriate antibiotic selection due to factors such as pathogen coverage, underlying disease, concomitant medications, drug metabolism and other issues.
Dr. William O’Riordan, chief medical officer of eStudySite, said, “These are encouraging results, especially given Baxdela’s full spectrum of coverage of Gram-positive and Gram-negative bacteria including MRSA, which is unique among quinolones. In addition, it performed well in this study against infections in difficult-to-treat patients, such as obese and diabetic patients, an important achievement.”
“Baxdela’s breadth of activity against difficult pathogens and in difficult patients, together with the favorable safety profile observed to date, and IV-to-oral dosing flexibility, should prove to be a valuable addition to the dwindling arsenal of antibiotics for serious infections,” said Chief Executive Officer Eugene Sun, M.D. “We are grateful to our investigators, patients, and Melinta team for successfully completing our phase III program. We anticipate submitting a New Drug Application to the FDA in the second half of this year for the treatment of serious hospital-treated skin infections.”
John Temperato, president and chief operating officer, said, “We look forward to to building a focused commercial organization offering a new treatment option for the nearly 3 million patients per year who are largely treated with therapies that do not meet key needs of pathogen coverage and tolerability. Having IV and oral dosage forms provides the potential for seamless and earlier hospital discharge, an important clinical and economic benefit. We are also eager to continue the ongoing clinical programs in hospital-treated community-acquired bacterial pneumonia (CABP) and complicated urinary tract infections (cUTI) as well. We expect that this will be the first of several follow-on indications we will seek for Baxdela.”
The pivotal phase III study, the second of a phase III program, was a randomized, double-blind study of patients with ABSSSI conducted under FDA Special Protocol Assessment. Patients in the Baxdela arm received 300mg of IV Baxdela every 12 hours for 6 doses followed by 450mg oral Baxdela every 12 hours. The recommended vancomycin dose was 15mg/kg of IV vancomycin every 12 hours based on actual body weight plus 1-2g of IV aztreonam every 12 hours. Duration of treatment in either the Baxdela or active control arms was 5-14 days based on the physician’s judgment. All patients were asked to return for a follow-up visit on day 14 ± 1 and a Late Follow-Up visit on days 21 to 28.