Date: 2011-04-18
Type of information: Initiation of preclinical development
phase: 2
Announcement: results
Company: Nabriva Therapeutics (Austria)
Product: BC-3781
Action
mechanism: antibioctic/pleuromulin derivative. BC-3781 is a pleuromutilin antibiotic with both oral and intravenous dose forms that is being developed for the treatment of bacterial diseases such as skin and skin structure infections and pneumonia.
Disease: acute bacterial skin and skin structure infections (ABSSSI)
Therapeutic area: Infectious diseases
Country: USA
Trial
details: The double blind randomized active controlled study was conducted at 23 centers in the USA and compared two doses of BC-3781 with Vancomycin. In 207 patients with ABSSSI who received 100mg or 150mg of BC-3781 or 1,000mg Vancomycin intravenously twice-daily. All patients had at least two signs of systemic infection (e.g. fever, raised level of white blood cells, C-reactive protein or lymphadenopathy). Approximately 50% of the patients had cellulitis and approximately 30% had abscesses with cellulitis. The average area of cellulitis was more than 160cm2. 60% of the ITT (intention to treat) population were microbiologically evaluable and of those 69% had documented MRSA infection.
Latest
news: Nabriva Therapeutics has announced the successful results of a Phase II clinical trial of BC-3781 in acute bacterial skin and skin structure infections (ABSSSI). In addition, following the recent FDA guidance, the early clinical response was assessed using a composite endpoint (cessation of spread of erythema with a lack of fever) at day 3: BC-3781 showed an excellent safety profile and was well tolerated. No drug related serious adverse events (SAE) were recorded for BC-3781 in any arm. BC-3781 at both doses showed lower incidences of drug related treatment emergent adverse events (TEAEs) compared to Vancomycin. BC-3781 is being developed for the treatment of serious skin infections and bacterial pneumonia caused by S. aureus, S. pneumoniae, H. influenza, Mycoplasma, Legionella and other bacteria, including drug resistant strains such as MRSA and Vancomycin resistant E. faecium. Nabriva Therapeutics will now move forward with plans to conduct phase III studies using both oral and intravenous administration in two indications: ABSSSI and hospital treated community-acquired pneumonia (HCAP).
BC-3781 had the same efficacy as Vancomycin, using both the traditional Test of Cure and newer early endpoints, and was safe and well tolerated. The results of this study provide the first proof of concept for the use of a pleuromutilin antibiotic systemically in man.
The results show that both doses of BC-3781 were comparable to Vancomycin in terms of clinical response at the primary end point, test-of-cure:
•90% of the patients (54/60) treated with 100mg of BC-3781,
•89% of the patients (48/54) treated with 150mg of BC-3781,
•92% of the patients (47/51) treated with 1000mg of Vancomycin.
•83% of patients achieving this endpoint with 150 mg BC-3781
•86% of patients achieving this endpoint with 100mg BC-3781
•80% of patients achieving this endpoint with Vancomycin
