New Antibiotic VIBATIV®▼ (telavancin) Targets Public Health Priority MRSA Infections for People with Hospital-Acquired Pneumonia Across Europe

BURTON-ON-TRENT, England, September 18, 2014 /PRNewswire/ --

Clinigen Group plc  (AIM: CLIN) today announced that the new first-in-class bactericidal, once-daily, injectable lipoglycopeptide antibiotic VIBATIV® (telavancin), is now available to prescribe in Europe for the treatment of adults with nosocomial pneumonia (also known as hospital acquired pneumonia - HAP), including ventilator associated pneumonia (VAP), known or suspected to be caused by methicillin-resistant Staphylococcus aureus (MRSA) when other alternatives are not suitable.

VIBATIV® is an innovative treatment for HAP in that it offers a dual mechanism of action to enable it to kill even drug resistant strains of Staphylococcus aureus.^[1] The first mechanism is similar to that of vancomycin; VIBATIV® binds to and prevents polymerisation of bacterial cell wall constituents, weakening the cell and causing cell death.  VIBATIV® also has a second mode of action where it interacts with the cell membrane, causing depolarisation; again leading to cell death. The drug's dual mechanism of action means that even a strain resistant to one of these mechanisms may be affected by the other mechanism, suggesting that VIBATIV® may be less prone to resistance than other antibiotics.  Rapidly bactericidal, VIBATIV® is a once daily IV administered antibiotic and does not require therapeutic drug level monitoring, unlike vancomycin.

30-70% of patients who acquire HAP currently die despite early and appropriate treatment, and the condition places a large burden on healthcare systems.^[2] A recent WHO surveillance report found that in some of the 36 European countries studied, prevalence of MRSA has been estimated at up to 60% of all studied S.aureus strains.^[3] The report notes that patients with infections caused by bacteria resistant to a specific antibacterial drug generally have an increased risk of worse clinical outcomes and death than those patients infected with the same bacteria not demonstrating a resistance pattern.3MRSA infections are recognised as a public health priority in the EU,and the extra in-hospital costs caused by MRSA across the EU are estimated to reach EUR 380 million every year.^[4] As a result of these high costs, both economic and human, there is increasing demand for new tools to combat infections caused by drug-resistant bacterial strains and the availability of new antibacterial agents is recognised as playing an important role in treating MRSA.

VIBATIV® is now available across Europe following the drug's Marketing Authorisation being reinstated by the European Commission earlier this year. The VIBATIV® approval was confirmed on the basis of data from clinical trials and compliance with GMP requirements.^[5]The Marketing Authorisation for VIBATIV® was suspended in 2012 as the previous single-source drug manufacturer did not meet the current Good Manufacturing Practice ("cGMP") requirements. It is important to note that no safety or efficacy concerns were raised over the product itself.

VIBATIV® successfully achieved the primary endpoint of clinical response versus vancomycin in Phase III non-inferiority studies of over 1,500 patients with hospital acquired pneumonia. VIBATIV®achieved higher clinical cure rates versus vancomycin in patients with pneumonia due to a monomicrobial Staphylococcus aureus infection.^[6] Higher cure rates were also observed for VIBATIV® in patients with strains of Staphylococcus aureus that displayed decreased susceptibility to vancomycin ([MIC ≥1μg/ml] [87% vs 74% p = 0.03 ]),^[6] suggesting that VIBATIV® may have the potential to treat infections caused by bacteria less or non-susceptible to antibiotics other than just methicillin. The efficacy data supporting VIBATIV® was confirmed in a post-hoc analysis of the Phase III studies (excluding patients with severe renal insufficiency at baseline) and showed that higher survival rates were observed in patients treated with VIBATIV® compared to vancomycin.^[7] In July 2014, NICE issued an Evidence Summary reviewing the role of VIBATIV® in treating HAP and VAP, summarising these data.^[8] NICE Evidence Summaries are quality-assured summaries of the best available evidence for new medicines, or existing medicines with new indications or a new formulation, considered to be of significance to the NHS.

The overall incidence of adverse events was similar for both vancomycin and VIBATIV®; the most common treatment-emergent adverse events in both treatment groups were taste disturbance, nausea, vomiting, diarrhoea, constipation, fungal infections, sleeplessness, headache, dizziness, raised blood levels of liver enzymes, itching, rash, tiredness, chills and kidney problems.^[5,6] In combination, the safety and efficacy data from the Phase III studies have shown that VIBATIV® has comparable tolerability with an overall non-inferiority to vancomycin in terms of clinical response, allied to higher cure rates in certain important groups of patients.

"HAP caused by MRSA is often more serious and difficult to treat than similar infections with more drug susceptible strains," said Professor Matteo Bassetti, Professor of Infectious Diseases, School of Medicine and Postgraduate School of Infectious Diseases, University of Udine, Italy. "We are increasingly seeing bacteria acquire resistance to antibiotics previously considered last resort treatments; we need more options to treat these extremely serious infections. The widespread availability of a new and effective antibiotic such as VIBATIV® is therefore very good news for Europe."

HAP is the most common cause of death among infections acquired in a hospital setting, and is the primary cause of death in Intensive Care Units (ICUs). Staphylococcus aureus is the leading cause of Gram-positive bacterial infection in European ICUs, and MRSA is thought to account for ≥ 25% of all Staphylococcus aureus strains in Europe although rates have been shown to vary considerably from country to country^[5]. There is a limited choice of licensed antibiotic therapies able to treat HAP/VAP caused by MRSA and other serious Gram-positive bacterial infections, with only vancomycin, linezolid and teicoplanin currently available in Europe and recommended for this use.^[6] The incidence of infections with S.aureus strains that are not responsive to treatment with vancomycin is increasing,^[9] and the first reported outbreak of infection due to linezolid- and methicillin-resistant S.aureus (LRSA) was reported in an intensive care unit in Spain.^[10] The growing problem of resistance makes it all the more important that new, effective agents are developed.

"The emergence of so-called 'super bugs' and increasing resistance among microbes to existing antibiotics has been recognised internationally as a major clinical challenge," said Peter George, Group Chief Executive Officer at Clinigen Group plc. "We are therefore extremely proud to be making this potentially life-saving medicine available across Europe for people who may have no other suitable option to fight a life-threatening infection."

Accessing VIBATIV®

For more information including prescribing information and how to order VIBATIV®, please visit http://www.vibativ.eu.  Clinigen is committed to delivering VIBATIV® to hospitals across mainland Europe within 48 hours

About VIBATIV® (telavancin)  

VIBATIV® is a bactericidal, once-daily, injectable lipoglycopeptide antibiotic with a dual mechanism of action whereby VIBATIV® both inhibits bacterial cell wall synthesis and disrupts bacterial cell membrane function. VIBATIV® is approved in the United States (US) for the treatment of adult patients with (i) complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains, and (ii) hospital-acquired and ventilator-associated bacterial pneumonia (HAP/VAP) caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. In September 2011, the European Commission granted Marketing Authorization for VIBATIV® for the treatment of nosocomial pneumonia (hospital-acquired), including ventilator-associated pneumonia, known or suspected to be caused by MRSA when other alternatives are not suitable. VIBATIV® was discovered and developed by Theravance, Inc., and transferred to Theravance Biopharma, Inc. in connection with the separation of the two companies in June 2014.

In May 2012, the European Commission suspended Marketing Authorization for VIBATIV® because the previous single-source drug product supplier did not meet the current Good Manufacturing Practice ("cGMP") requirements for the manufacture of VIBATIV®. In March this year the European Commission reinstated the marketing authorisation for VIBATIV® as consistent product supply was re-established in accordance with European Commission requirements. Theravance Biopharma Antibiotics, Inc. has granted Clinigen exclusive commercialization rights to VIBATIV® in the EU and certain other European countries (including Switzerland and Norway).

For further information, including prescribing information please visit http://www.vibativ.eu

About Clinigen 

The Clinigen Group is a specialty global pharmaceutical company headquartered in the UK, with offices in the US and Japan. The Group has three operating businesses; Specialty Pharmaceuticals (Clinigen SP), Clinical Trials Supply (Clinigen CTS), and Global Access Programs (Clinigen GAP).

Clinigen GAP develops and implements global access programs for biotechnology and pharmaceutical companies and has provided access to unlicensed, licensed and end-of-lifecycle products to thousands of patients. Clinigen has experience in the implementation of more than 30 access programs worldwide.

Clinigen SP is focused on acquiring its own intellectual property in licensed, niche, hospital-only critical care medicines, increasing the value of these medicines by developing new formulations and indications, then registering and marketing them in defined global markets.

For more information, please visit http://www.clinigengroup.com or http://www.vibativ.eu

References 

1. Sahm DF, Benton BM, Jones ME et al. Telavancin demonstrates a low potential for in vitro selection of resistance among key target Gram-positive species. Poster C1-0681, Program and Abstracts of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 27–30 (2006)

2. Scott LJ. Telavancin: A review of its use in patients with nosocomial pneumonia. Drugs. 2013:73;1829-1839

3. WHO. Antimicrobial resistance: global report on surveillance 2014. Available from: http://who.int/drugresistance/documents/surveillancereport/en/ [accessed August 2014]

4. Kock R, Becker K, Cookson B et al. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Eurosurveillance. 2010;15(41)

5. VIBATIV® EU Summary of Product Characteristics. Last updated March 2014. Available online from the European Medicines Agency at http://www.ema.europa.eu/  

6. Rubinstein E, Lalani T, Corey GR et al. Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens. Clinical Infectious Diseases. 2011;52(1):31–40

7. Torres A, Rubinstein E, Corey GR et al. Analysis of Phase 3 telavancin  nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure. Journal of Antimicrobial Chemotherapy. 2014; 69(4): 1119–1126

8. NICE Evidence Summary: Hospital-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus: telavancin. Available from: http://publications.nice.org.uk/hospital-acquired-pneumonia-caused-by-methicillin-resistant-staphylococcus-aureus-telavancin-esnm44 [accessed August 2014]

9. Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by Methicillin-Resistant Staphylococcus aureus. Clinical Infectious Diseases. 2008; 46:S378–85

10. Sanchez Garcia M, De la Torre MA, Morales G et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. The Journal of the American Medical Association. 2010; 9;303(22):2260-4. doi: 10.1001/jama.2010.757