Cempra Pharmaceuticals Presents New Data On TAKSTA™ (CEM-102, Sodium Fusidate) At The 50th Interscience Conference

Main Category: MRSA / Drug Resistance
Also Included In: Clinical Trials / Drug Trials;  Conferences;  Pharma Industry / Biotech Industry
Article Date: 10 Sep 2010 - 4:00 PDT


Cempra Pharmaceuticals announced abstracts to be presented on its oral anti-MRSA antibiotic, TAKSTA (sodium fusidate, formerly CEM-102), at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 12 to 15, 2010, in Boston. Data to be presented demonstrate that TAKSTA showed clinical success rates and tolerability comparable to oral linezolid. Presentations will also provide additional data that demonstrate the activity of TAKSTA against MRSA strains and the effectiveness of TAKSTA's against S. pyogenes.

Sodium fusidate has an established track record of efficacy and safety outside the U.S. for treating gram-positive skin infections, including MRSA. The novel proprietary oral dosing regimen under development by Cempra in the U.S. is based on extensive PK-PD modeling that was validated in preclinical and Phase 1 single- and multi-dose clinical trials. The PK-PD modeling employed defined drug loads chosen to optimize the efficacy and spectrum of activity while minimizing the selection of resistant organisms. In the U.S., TAKSTA is in clinical development for the treatment of aBSSSI, caused by gram positive bacteria, especially drug-resistant strains such as MRSA.

"Most of the antibiotics approved for use against MRSA are injectable agents that must be administered in the hospital," said Prabhavathi Fernandes, Ph.D., chief executive officer of Cempra. "New agents that effectively and safety treat complicated MRSA infections with oral therapy are needed so that there is an option for outpatient treatment rather than in-hospital intravenous antibiotic administration. We believe that the emerging profile of TAKSTA, including its loading dose regimen, suggests that it could become an important therapeutic option."

TAKSTA shows clinical success rates and tolerability comparable to oral linezolid in a Phase 2 study in aBSSSI patients (Moriarty et al., Abst. L1-1762)

The Phase 2 randomized, double-blind and multi-center study evaluated the efficacy and safety of oral TAKSTA. TAKSTA was administered 1,500 mg twice-daily on day one followed by 600 mg twice daily thereafter. Oral linezolid was dosed 600 mg twice daily. Both were dosed for 10 to 14 days, in 155 patients with either cellulitis (n=100) or wound infections (n=55). Primary endpoints were clinical success in the intent-to-treat (ITT) and clinically evaluable (CE) populations at the test of cure visit. Clinical success rates of both compounds were comparable. S. aureus were isolated in 72 percent of patients, 70 percent of which were MRSA. The rates of adverse events (AEs) were comparable in both treatment groups. The results of this study demonstrate that TAKSTA's clinical success rates and tolerability are comparable to linezolid.

TAKSTA continues to demonstrate potent activity against hospital- and community-acquired MRSA strains

MRSA continues to be a serious pathogen both in hospitals and in the community. TAKSTA has showed potent anti-MRSA activity against multiple strains of this pathogen from several geographic areas. Several presentations add to the understanding of its spectrum of activity.

Pillar et al. (Abst. E-1559) tested TAKSTA against a collection of hospital- and community-acquired MRSA strains many of which are also resistant to vancomycin, linezolid or daptomycin. TAKSTA demonstrated potent activity against most MRSA strains with the exception of one vancomycin intermediate sensitive strain, two daptomycin and one linezolid non-susceptible isolate.

Two studies investigated TAKSTA's in vitro anti-MRSA activity against several other anti-infectives (mostly administered only intravenously). Todd et al., (Abst. E-1558) tested 40 MRSA strains isolated from cystic fibrosis patients. TAKSTA was shown to be very potent against all 40 strains and it was the only agent tested in this study, with the exception of linezolid, which has an orally-administered dosage form.

Dubois and Fernandes (Abst. E-1561) compared the activity of TAKSTA against several antibiotics, including azithromycin, telithromycin, levofloxacin, linezolid and doxycycline against 272 MRSA strains. TAKSTA was the most potent against all MRSA strains with the exception of a ciprofloxacin-resistant MRSA strain, in which it showed activity comparable to telithromycin.

Development of resistance to fusidic acid has been viewed as a concern though, in reality, in Europe where fusidic acid has been used for a few decades, high-level resistance (fusA) is only found in about 3 percent of strains and low-level resistance (fusB, fusC and fusD) in no more than 7 percent of strains (Castanheira, M. et al., Antimicrob. Agents Chemother., 2010). Kosowska-Shick et al. (Abst. E-1557) tested the ability of TAKSTA and two comparators, linezolid and daptomycin, to select for resistance in eight MRSA strains and one MSSA strain. The study showed that resistance to TAKSTA is rare with serial passages at clinically relevant plasma concentrations.

Tsuji, et al. (Abst. A1-021) tested the pharmacokinetics-pharmacodynamics of TAKSTA against Streptococcus pyogenes in a hollow fiber in vitro infection model. S pyogenes are frequently found in skin infections either alone or with S. aureus. S. pyogenes has a higher MIC than S. aureus (4-8 ug/mL). However the authors demonstrated that a range of regimens, including one that mimics the loading dose regimen, were effective against S. pyogenes and that no resistance was observed.

About TAKSTA™

TAKSTA, (sodium fusidate) is a novel class of antibiotic with an established history of safety and efficacy outside the United States. TAKSTA is being developed as an NCE in the U.S. for aBSSSI. Clinical trials with TAKSTA employ a proprietary front-loading oral regimen designed to increase potency, increase coverage and minimize resistance development. Cempra believes that TAKSTA will be an important addition to anti-MRSA therapies based on the following:

-- Sodium fusidate is orally active against gram-positive bacteria, including all S. aureus strains such as HA-MRSA and CA-MRSA

-- TAKSTA employs a novel and proprietary PK-PD-based dosing regimen of sodium fusidate that optimizes efficacy and minimizes the risk of resistance development

-- Sodium fusidate is the only compound within the fusidane class and therefore is unlikely to select for cross-resistance to other classes of antibiotics

-- Sodium fusidate's safety has been well documented even when used for long periods of time (over one year) to treat osteomyelitis and other serious infections

-- Sodium fusidate has been used safely in children including neonates in countries where it is marketed

About 60 to 80 percent of the 13 million acute skin structure infections that occur in the U.S. each year are infected with MRSA. There is a growing need for an oral anti-MRSA drug that is safe, effective and is safe for long-term administration.

Source: Cempra Pharmaceuticals

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