Saturday, April 23, 2011

Nabriva announces positive results in a phase II ABSSSI trial

     Finally I have some good news to share.  On a personal note, I have been working with
Nabriva since 2005, well before they were spun out of Novartis’ Sandoz in Vienna in January 2006.  I feel like their products are partly my children.  Nabriva recently announced the completion of their phase II clinical trial in acute bacterial skin and skin structure infections (ABSSSI, as the FDA now says).  This is the first such trial to be completed using the FDA designated guidelines as a template.  Their data, when fully made public, will allow a comparison of the proposed FDA early endpoints to ultimate clinical outcome for the first time.  (Hint – it might not be so straightforward).  If you can’t tell – I am very proud of their achievement.

BC-3781 is the first pleuromutilin antibiotic to be efficacious in humans.  Pleuromutilins were discovered around 1950 at Columbia University in New York.  A pleuromutilin was approved for use in animals around 1979.  In spite of many years of effort within many pharmaceutical c0mpanies, no one was able to identify a pleuromutilin that could be used systemically in humans prior to Nabriva’s program. This, by itself, is a remarkable achievement.  BC-3781 is, in fact, the second pleuromutilin Nabriva has studied in clinical trials. BC-3205 was studied in a number of phase I trials in an oral formulation, but BC-3781 was taken all the way through phase II trials.

In their Phase II trial, Nabriva studied seriously ill patients with a variety of skin infections.  Patients with abscesses were required to have a large area of cellulitis around the abscess and even so, such abscesses were limited to 30% of the study population. 50% of the study population had cellulitis with an average area of over 160 sq cm.  Those with wound infection were also required to have cellulitis. All patients had at least two signs of systemic infection (e.g. fever, raised level of white blood cells, C-reactive protein or lymphadenopathy).  60% of treated patients had a pathogen isolated and almost 70% of those were MRSA.

     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:
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

     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.

     The safety profile of 3781 was excellent.  BC-3781 has a bacterial spectrum which would include a broad spectrum of respiratory pathogens including atypicals and Legionella.  Therefore, 3781 would make a good choice for empiric monotherapy for community-acquired respiratory infection as well as skin infections.  Nabriva has plans to pursue both indications in Phase III trials.

     So – I offer my congratulations to Nabriva and to those of us who desire new antibiotics for our arsenal against resistant infections.

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