Efficacy

BAXDELA Clinical Trials

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 aztreonama

vancomycin plus aztreonam
(n=427)

vancomycin
15 mg/kg plus aztreonama

PRIMARY Endpoint: At least 20% reduction in lesion size at 48-72 hours

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

aVancomycin 15 mg/kg q12h was recommended. Monitoring was done on days 2 and 6 with target trough concentration of 15-20 µg/mL

Baseline Characterisitics: Pooled Data, Trials 1 and 2

Patient Population1510 patients across 2 trials

Patient population infographic for BAXDELA trial - males
62% Male
Patient population infographic for BAXDELA trial - females
38% Female
Average Age
Patient population infographic for BAXDELA trial - ages

Relevant Comorbidities

Patient comorbidities bar chart for BAXDELA trial

Baseline Infection Type1

Baseline infection chart for BAXDELA trial

Systemic Signs of Infection1

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.

Lesion Size1

Overall Mean (SD) Surface Area of Erythema
(measured by digital planimetry)

321 cm2 (311.57)

SD = standard deviation.
1. Data on file (included in BAXDELA New Drug Application). Melinta Therapeutics, Inc.; 2016.

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

Primary Endpoint in Phase 3 Trials

Objective clinical response at 48-72 hoursa 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) IN THE MEFUI POPULATION

BAXDELA monotherapy 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 (included in BAXDELA New Drug Application). Melinta Therapeutics, Inc.; 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 Pooled data from phase 3 trials

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

Gram-Positive Pathogens

BAXDELA Vancomycin + aztreonam

CLINICAL RESPONSE AT 48-72ha

% OF PATIENTS (n/N)

BAXDELA gram-positive pathogen Staphylococcus aureus clinical response chart BAXDELA gram-positive pathogen MSSA clinical response chart BAXDELA gram-positive pathogen MRSA clinical response chart BAXDELA gram-positive pathogen Staphylococcus haemolyticus clinical response chart BAXDELA gram-positive pathogen Staphylococcus lugdunensis clinical response chart BAXDELA gram-positive pathogen Enterococcus faecalis clinical response chart BAXDELA gram-positive pathogen Staphylococcus agalactiae clinical response chart BAXDELA gram-positive pathogen Staphylococcus anginosus group clinical response chart BAXDELA gram-positive pathogen Staphylococcus pyogenes clinical response chart

aObjective clinical response was defined as a 20% or greater decrease in lesion size as determined by digital planimetry of the leading edge of erythema at 48 to 72 hours after initiation of treatment.
bDiscrepancy in the total numbers is due to multiple subjects having both MRSA and MSSA isolates. MRSA = methicillin-resistant S aureus; MSSA = methicillin-susceptible S aureus

INVESTIGATOR-ASSESSED SUCCESS AT DAY 14 (+/- 1)a

% OF PATIENTS (n/N)

BAXDELA gram-positive pathogen Staphylococcus aureus investigator-assessed success chart BAXDELA gram-positive pathogen MSSA investigator-assessed success chart BAXDELA gram-positive pathogen MRSA investigator-assessed success chart BAXDELA gram-positive pathogen Staphylococcus haemolyticus investigator-assessed success chart BAXDELA gram-positive pathogen Staphylococcus lugdunensis investigator-assessed success chart BAXDELA gram-positive pathogen Enterococcus faecalis investigator-assessed success chart BAXDELA gram-positive pathogen Staphylococcus agalactiae investigator-assessed success chart BAXDELA gram-positive pathogen Staphylococcus anginosus group investigator-assessed success chart BAXDELA gram-positive pathogen Staphylococcus pyogenes investigator-assessed success chart

aSuccess was defined as complete or near-complete resolution of signs and symptoms with no further antibacterial therapy needed at follow-up visit (day 14 +/- 1).
bDiscrepancy in the total numbers is due to multiple subjects having both MRSA and MSSA isolates.

Gram-Negative Pathogens

BAXDELA Vancomycin + aztreonam

CLINICAL RESPONSE AT 48-72ha

% OF PATIENTS (n/N)

BAXDELA gram-negative pathogen Escherichia coli clincal response chart BAXDELA gram-negative pathogen Enterobacter cloacae clinical response chart BAXDELA gram-negative pathogen Klebsiella pneumoniae clinical response chart BAXDELA gram-negative pathogen Pseudomonas aeruginosa clinical response chart

aObjective clinical response was defined as a 20% or greater decrease in lesion size as determined by digital planimetry of the leading edge of erythema at 48 to 72 hours after initiation of treatment.

INVESTIGATOR-ASSESSED SUCCESS AT DAY 14 (+/- 1)a

% OF PATIENTS (n/N)

BAXDELA gram-negative pathogen Escherichia coli investigator-assessed success chart BAXDELA gram-negative pathogen Enterobacter cloacae investigator-assessed success chart BAXDELA gram-negative pathogen Klebsiella pneumoniae investigator-assessed success chart BAXDELA gram-negative pathogen Pseudomonas aeruginosa investigator-assessed success chart

aSuccess was defined as complete or near-complete resolution of signs and symptoms with no further antibacterial therapy needed at follow-up visit (day 14 +/- 1).

BAXDELA is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.