Efficacy

BAXDELA™ Monotherapy Proven as Effective as Vancomycin Plus Aztreonam

Phase 3 Noninferiority Trials Design Evaluated in 2 randomized, double-blind, multicenter trials of 1510 patients

Assessment at Baseline: Lesion size ≥75 cm2

TRIAL 1: IV Only BAXDELA IV
(n=331)

TRIAL 2: IV to Oral BAXDELA IV to oral
(n=423)

BAXDELA 300 mg IV q12h

BAXDELA 300 mg IV q12h for 6 doses, then switched to 450 mg oral q12h

Vancomycin plus aztreonam
(n=329)

vancomycin
15 mg/kg plus aztreonam

Vancomycin plus aztreonam
(n=427)

vancomycin
15 mg/kg plus aztreonam

PRIMARY Endpoint: At 48-72 h, reduction in lesion size ≥20%

SECONDARY Endpoint: At day 14 (+/- 1) follow-up, investigator-assessed clinical success defined as complete or near-complete resolution of signs and symptoms with no further antibacterial therapy needed

Baseline Characterisitics: Pooled Data, Trials 1 and 2

Patient Population1510 patients across 2 trials

Patient population infographic for BAXDELA trial - males
63% Male 953 men
Patient population infographic for BAXDELA trial - females
37% Female 557 women
Average Age
Patient population infographic for BAXDELA trial - ages

Relevant Comorbidities

Patient comorbidities bar chart for BAXDELA trial

Baseline Infection Type

Baseline infection chart for BAXDELA trial

Systemic Signs of Infection

Systemic infections graph for BAXDELA trial

aWith the exception of one patient, all patients randomly assigned to treatment met the requirement for having at least 2 systemic signs of infection.

BAXDELA Monotherapy Demonstrated Efficacy in IV-Only and IV-to-Oral Trials

Primary Endpoint in Phase 3 Trials

Objective responsea at 48-72 hours in the ITT population

At least 20% reduction in lesion size.a

TREATMENT DIFFERENCE (2 sided, 95% CI)
TRIAL 1:
−2.6 (−8.8, 3.6)
TRIAL 2:
3.1 (−2.0, 8.3)

BAXDELA 300 mg IV q12h vs comparator

BAXDELA 300 mg Vancomycin 15 mg/kg + aztreonam
BAXDELA IV primary endpoint chart

BAXDELA 300 mg IV q12h for 6 doses, then a mandatory switch to oral BAXDELA 450 mg q12h vs comparator

BAXDELA 300 mg, then 450 mg oral Vancomycin 15 mg/kg + aztreonam
BAXDELA IV-to-oral primary endpoint chart

CI = confidence interval; ITT = intention-to-treat.
aDetermined by digital planimetry of the leading edge of erythema without other reasons for failure (use of another antibiotic or surgical procedure to treat for lack of efficacy). Missing patients were treated as failures in the ITT analysis set.

Secondary Endpoint in Phase 3 Trials

Investigator assessment of response at Follow-Up Visit (day 14 +/− 1) in the CE population

Success was defined as cure + improved where patients had complete or near-complete resolution of signs and symptoms, with no further antibiotic therapy needed.

TREATMENT DIFFERENCE (2 sided, 95% CI)
TRIAL 1:
−0.9 (−4.3, 2.4)
TRIAL 2:
-0.9 (−3.9, 2.0)

BAXDELA 300 mg IV q12h vs comparator

BAXDELA 300 mg IV Vancomycin 15 mg/kg + aztreonam
BAXDELA IV treatment difference chart

BAXDELA 300 mg IV q12h for 6 doses, then a mandatory switch to oral BAXDELA 450 mg q12h vs comparator

BAXDELA 300 mg IV, then 450 mg oral Vancomycin 15 mg/kg + aztreonam
BAXDELA IV-to-oral treatment difference chart

CI = confidence interval; CE = clinically evaluable consisted of all ITT patients who had a diagnosis of ABSSSI, received at least 80% of expected doses of the study drug, did not have any protocol deviations that would affect the assessment of efficacy, and had investigator assessment at the Follow-Up Visit.

BAXDELA Monotherapy Effective Against MRSA

MRSA INFECTION: ERADICATION AT FOLLOW-UP VISIT (DAY 14 +/− 1) Phase 3 studies

BAXDELA monotherapy was comparable to vancomycin plus aztreonam in the eradication of MRSA infection

Analysis set consisted of patients who were Microbiologically Evaluable at Follow-Up visit for Investigator-assessed response (MEFUI)

POOLED DATA TRIALS 1 AND 2

BAXDELA 300 mg IV (Trial 1); BAXDELA 300 mg IV, then 450 mg oral (Trial 2) Vancomycin 15 mg/kg + aztreonam

Microbiological Response at Follow‑up in Patients With MRSA Infections

BAXDELA treatment response chart of patients with MRSA

Data on file. Melinta Therapeutics, 2016.

In the Microbiological ITT (MITT) population, microbiological response was as follows: BAXDELA, 122/144 (84.7%); vancomycin plus aztreonam, 116/141 (82.3%)

Microbiological response for all groups was defined as eradicated or persisted. Each group included both documented and presumed results.

  • Documented: Baseline pathogen was or was not present in cultures of the original site of infection at follow-up visit.
  • Presumed: Baseline pathogen present, but no material available for culture/no culture done at follow-up visit; investigator assessed response.

BAXDELA Monotherapy Effective Against Susceptible Gram-Positive and Gram-Negative Pathogens

Outcomes By Baseline Pathogen (Day 14 +/− 1) Investigator-assessed success at follow-up visit / Pooled data from phase 3 trials

Analysis set: Microbiological ITT (MITT) consisted of all randomized patients who had a baseline pathogen identified that is known to cause ABSSSI

Success was defined as complete or near-complete resolution of signs and symptoms with no further antibacterial therapy needed at follow-up visit.

Gram-Positive Pathogens

Staphylococcus BAXDELA
n/N		 Comparator
n/N
S aureus 275/319 (86.2%) 269/324 (83.0%)
methicillin-susceptible (MSSA)a 154/177 (87.0%) 153/183 (83.6%)
methicillin-resistant (MRSA)a 122/144 (84.7%) 116/141 (82.3%)
S lugdunensis 10/11 (90.9%) 8/9 (88.9%)
S haemolyticus 13/15 (86.7%) 7/8 (87.5%)
aDiscrepancy in the total numbers is due to multiple subjects having both MRSA and MSSA isolates.
Enterococcus and Streptococcus Pathogens BAXDELA
n/N		 Comparator
n/N
E faecalis 9/11 (81.8%) 14/16 (87.5%)
S agalactiae 12/14 (85.7%) 11/12 (91.7%)
S anginosus group 54/64 (84.4%) 47/61 (77.0%)
S pyogenes 21/23 (91.3%) 16/18 (88.9%)

Gram-Negative Pathogens

Pathogens BAXDELA
n/N		 Comparator
n/N
Escherichia coli 12/14 (85.7%) 18/20 (90.0%)
Enterobacter cloacae 12/14 (85.7%) 10/11 (90.9%)
Klebsiella pneumoniae 20/22 (90.9%) 21/23 (91.3%)
Pseudomonas aeruginosa 11/11 (100%) 12/12 (100%)

Next: Safety & Tolerability

Melinta Therapeutics, Inc. - The Antibiotics Company

For additional information about BAXDELA, call Melinta Therapeutics at 1-844-MELINTA (1-844-635-4682) or contact the US Food and Drug Administration at 1-888-INFO-FDA (1-888-463-6332).

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