REINACH and BASEL, Switzerland, March 29, 2007 /PRNewswire-FirstCall/ -- Arpida Ltd. today announced promising results of "first-in-man" studies with AR-709. These radiolabelled Human Microdose studies included a total of 19 healthy male volunteers.
This groundbreaking study is the first ever using Microdosing for the determination of drug concentrations in lung compartments. The results showed that AR-709 achieves high concentrations in bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM), the three key compartments of the lungs where pathogens can reside and replicate. Moreover, the results of the studies show that AR-709 exhibited a large volume of distribution and a long half life in man. Oral bioavailability was potentially low but this could be due to the low dose, poor absorption or extensive metabolism.
The studies were conducted at Hammersmith Medicines Research Ltd (London, UK) under MHRA regulatory authorisation and were coordinated by Xceleron Ltd (York, UK), the exploratory clinical development specialist and world leader in the field of Human Microdosing.
Dr Sergio Lociuro, Head of Research of Arpida Ltd. commented "I am very pleased with the results of this first human trial with AR-709. They clearly show that the compound distributes well throughout the body and more importantly in the lungs. In a substantial number of cases, community-acquired respiratory tract infections, caused by S. pneumoniae, require hospitalisation and intravenous therapy. AR-709 appears to have the necessary characteristics to eradicate the microorganisms that can result in serious infections. For cases not requiring hospitalisation and/or to accelerate patient discharge from the hospital, targeted delivery, e.g. via inhalation, could provide a valid and promising alternative to administration via the oral route. Altho ugh the oral route is not excluded as an option, targeted delivery, which could be developed with appropriate players in this field, could have the added benefit of avoiding unnecessary systemic exposure."
AR-709 is a novel DHFR inhibitor with an outstanding microbiological activity against streptococci in general and, importantly, against multi-drug resistant Streptococcus pneumoniae, the most relevant pathogen in community-acquired pneumonia. Moreover the compound has been shown to be highly effective in preclinical pneumonia models of infection both intravenously and by the oral route.
Arpida is completing the appropriate studies in order to initiate tolerability studies in humans.
About Streptococcus pneumoniae and pneumonia
Streptococcus pneumoniae is the most feared bacterium that causes pneumonia in the community setting. Since the first reports of Streptococcus pneumoniae resistance to penicillin in 1967, the number of multiple antibiotic resistant organisms has rapidly increased world-wide, reaching peaks of 80% in regions of some countries in 1998. In the USA, up to 40% of the bacterial strains causing these infections are resistant to at least one drug, and 15% are resistant to three or more commonly used drugs. Streptococci cause 500,000 cases of pneumonia each year, and 7 million cases of ear infections and sinusitis in the USA alone. Recently, epidemics of diseases caused by Streptococcus pneumoniae have reappeared in settings such as chronic care facilities, military camps and day care centers, a situation not seen since the pre-antibiotic era.
This increasing number of antibiotic-resistant pathogens is of specific concern to physicians in the area of respiratory tract infection. In the community setting, 67% of antibiotic use in adults and 87% in children is for the treatment of RTIs. The antibacterial market in the community settings is estimated at USD18 billion with pneumonia acquired in the community setting acc ounting for approximately 4.5 million medical visits per year in the USA alone and resulting in annualised treatment costs in excess of USD8 billion.
About inhaled antibiotics
Inhaled antibiotics have so far been primarily used in the setting of Cystic Fibrosis or in the prophylaxis of Pneumocystis jiroveci. However, because they deliver high drug concentrations at the site of infection with negligible systemic absorption, they are the logical complements to standard intravenous therapy for severe nosocomial pneumonias and in the treatment of severe healthcare-associated pneumonia caused by multiresistant organisms.
About Human Microdosing
Human Microdosing involves the administration of sub-pharmacological doses of candidate drugs to human subjects without extensive animal testing. The Microdosing / "first-in-man" approach was pioneered by Xceleron and is now accepted as a valuable tool in drug screening. Use of the innovative "first-in-man" / Human Microdose concept allows companies to gain key information 12-18 months faster than using the conventional drug development paradigm.
About Arpida Ltd.
Arpida is a biopharmaceutical company with research facilities near Basel, Switzerland and in the USA. It focuses on the discovery and development of novel antibiotic drugs that seek to overcome the growing problem of bacterial resistance.
Arpida's leading product candidate is intravenous iclaprim, a broad-spectrum antibiotic that targets severe infections requiring hospital treatment, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). In November 2006, intravenous iclaprim has successfully completed its first Phase III trial in the treatment of cSSSI (complicated skin and skin structure infections). In March 2007, patient enrolment into the Phase III programme was completed. The US Food and Drug Administration has granted fast track status to intravenous iclaprim for the treatment of cSSSI.
An oral formulation of iclaprim has successfully completed three Phase I trials: a radiolabelled ADME study (absorption, distribution, metabolism and excretion), a Phase I bioavailability trial with a solution and one with a capsule formulation. Arpida believes that the availability of an oral formulation could potentially fulfil an important clinical medical need for the treatment of serious bacterial infections, particularly those caused by MRSA. Iclaprim could be offered not only as an intravenous therapy for hospital use in acute situations, but also as an oral formulation, allowing early patient discharge and outpatient treatment. This switch should be a valuable instrument in reducing healthcare costs and enhancing patient comfort.
Arpida's third most advanced programme, AR-709, targets upper and lower respiratory tract infections acquired in the community setting. AR-709 exhibited potent activity against 611 pneumococcal clinical isolates from Europe, the USA and Asia irrespective of the mechanisms of resistance to currently used drugs. Arpida received authorisation to enter first-in-man studies with AR-709 in the UK in the second half of 2006.
An additional compound, AR-2474, has achieved in vivo proof of concept. AR-2474 has been shown to be highly effective in eradicating MRSA in preclinical models of skin infection and nasal carriage.
Moreover, the company has several other leads in optimisation and additional discovery programmes derived from its own discovery platform at various research stages.
This press release contains specific forward-looking statements, e.g. statements including terms like believe, assume, expect or similar expressions. Such forward-looking statements are subject to known and unknown risks, uncertainties and other factors which may result in a substantial divergence between the actual results, financial situation, development or performance of the company and those explicitly or implicitly presumed i n these statements. Against the background of these uncertainties readers should not place undue reliance on forward-looking statements. The company assumes no responsibility to update forward-looking statements or to adapt them to future events or developments.
For further information please contact: Arpida Dr Khalid Islam, President and CEO Tel: +41-61-417-96-60 Harry Welten, MBA, CFO and Senior Vice President Tel: +41-61-417-96-65 Paul Verbraeken, Head of Corporate Communications Tel: +41-61-417-96-83
CONTACT: For further information please contact: Arpida, Dr Khalid Islam,President and CEO, Tel: +41-61-417-96-60, Harry Welten, MBA, CFO and SeniorVice President, Tel: +41-61-417-96-65, Paul Verbraeken, Head of CorporateCommunications, Tel: +41-61-417-96-83
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