Arpida Reports Positive Results of Second Pivotal Phase Iii Trial with Intravenous Iclaprim in CSSSI
Phase Iii Programme with Intravenous Iclaprim in Its First Indication Completed Regulatory Filing Expected Before Year-end 2007
* Iclaprim achieves pre-specified primary efficacy endpoint in
its second Phase III trial
* Safety profile confirmed
REINACH / BASEL, Switzerland, July 15, 2007- Arpida Ltd. (SWX: ARPN) today announced results from the second pivotal Phase III trial with intravenous iclaprim in patients with complicated skin and skin structure infections (cSSSI). In this trial, called ASSIST-2 (Arpida's Skin and Skin Structure Infection STudies), iclaprim was compared to linezolid, marketed by Pfizer as Zyvox®. The pre-specified primary efficacy endpoint of statistical non-inferiority in the clinical cure rate at the Test-Of-Cure (TOC) visit was achieved, confirming the outcome of ASSIST-1. Moreover, iclaprim's safety profile demonstrated in ASSIST-1 was confirmed in ASSIST-2.
Professor John G. Bartlett, MD, Division of Infectious Diseases
at the Johns Hopkins University School of Medicine, former
President of Infectious Diseases Society of America (IDSA) and
currently Chair of the Antimicrobial Availability Task Force of
IDSA, said: "MRSA is a raging epidemic in the hospital and in the
community throughout much of the world. We need more and better
antibiotics. Iclaprim is a novel member of the diaminopyrimidine
class of antibiotics, a class that we are familiar with and have
successfully used for treating patients for decades. The outcome of
ASSIST-1 and ASSIST-2 holds substantial promise for use of iclaprim
in serious hospital infections based on both safety and efficacy."
Dr Paul Hadvary, Head of Development of Arpida Ltd., commented "I
am delighted with the outcome of the ASSIST-2 trial and the fact
that both pivotal Phase III trials, ASSIST-1 and ASSIST-2, have
achieved their pre-specified primary endpoint. These exciting
results obtained with iclaprim will be shared with the medical and
scientific community via platforms such as the ICAAC conference in
September and the IDSA conference in October this year."
Dr Khalid Islam, President and CEO of Arpida Ltd. added "I would like to take this occasion to thank the patients, investigators and their staff, third party vendors and the Arpida staff for their contributions to the successful outcome of the trial and our shareholders for their confidence and support. We look to discuss the data with the regulatory authorities to define the path forward for the filing of a New Drug Application (NDA) which we expect to take place in the course of this year."
Both ASSIST-1 and ASSIST-2 have met their pre-specified efficacy endpoints at the Test-of-Cure. Of the total of 494 patients that were enrolled and treated in the Intent-To-Treat population (ITT, all patients that were randomised and received at least one dose of the study drugs; 251 in the iclaprim arm and 243 in the linezolid arm) in ASSIST-2, the vast majority had extensive cellulitis, abscesses, ulcers, burns or wounds. The overall clinical cure rates for the ITT population of 494 patients, were 84.9% and 87.2% for iclaprim and linezolid, respectively. Staphylococcus aureus was the most common baseline pathogen (about 60%) and up to 50% of the isolates were methicillin-resistant strains (MRSA). The microbiological eradication rates for MSSA were 83.5% and 84.7% for iclaprim and linezolid respectively and for MRSA 77.0% and 80.0%, respectively.
The results are very similar to those observed in ASSIST-1. For the Modified ITT population (MITT, patients with an infecting Gram-positive baseline pathogen), the clinical cure rates were 83.3% and 85.9% for iclaprim and linezolid, respectively. In a preliminary analysis of the clinically evaluable population (CE) the cure rates were 89.6% and 96.4% for iclaprim and linezolid respectively. The patient population in the two arms was well-balanced for patient characteristics, e.g., race, gender, age etc.
However, there was an imbalance in the number of patients who received prohibited antibiotic co-medication which was substantially higher in the linezolid arm leading to exclusion from the CE population. Additionally, the larger sizes of infection appeared to be more frequent in the iclaprim arm when compared with the linezolid arm. Further analyses will be undertaken.
As in the previous study, the proportion of patients reporting adverse events, that were judged by the investigator to be possibly/probably related to treatment, was lower in the iclaprim arm than in the linezolid arm (27.9% of the ITT population for iclaprim versus 34.6% for linezolid). In the iclaprim arm, one possibly/probably treatment related serious adverse event was reported. The most frequent adverse events related to treatment were diarrhoea (4.4% for iclaprim versus 6.6% for linezolid) nausea (2.4% for iclaprim versus 6.6% for linezolid), headaches (3.6% for iclaprim versus 4.5% for linezolid) and pruritis (2.8% for iclaprim versus 2.9% for linezolid). A 6 ms QT change from pre-treatment values was observed for iclaprim, after correcting for comparator control (7.8 ms for iclaprim versus 1.8 ms for linezolid).In two patients in the iclaprim arm a QTc increase relative to pre-treatment of more than 60ms was observed. No cardiac events were attributable to QTc prolongation in the iclaprim arm, while in the linezolid arm, one patient was withdrawn due to treatment emergent cardiovascular abnormalities. ASSIST-2 Study Design The international, blinded, comparator controlled, multicenter, ASSIST-2 trial enrolled 494 patients in 59 centres in 9 countries (USA, Canada, 6 EU countries and South Africa) in the Intent-To-Treat (ITT) population.
The primary endpoint of the study was the clinical cure rate at the Test-Of-Cure visit, based on criteria set forth in the protocol previously reviewed by the US and European regulatory authorities. The trials were designed to compare the efficacy and safety of intravenous iclaprim with that of the market leader linezolid (marketed by Pfizer as Zyvox®). - ends -
Conference Call Arpida will host a conference call to discuss
these trial results on Monday 16 July 2007, at 3 pm CET. The
dial-in numbers are: +41 (0) 91 610 56 00 (Europe) +44 (0) 207 107
0611 (UK) + 1 (1) 866 291 4166 (USA) The conference call (Call ID
397, followed by the #) will be available for play-back for 48
hours after the call by dialling: +41 (0) 91 612 43 30 (Europe) +44
(0) 207 108 6233 (UK) + 1 (1) 866 416 2558 (USA) Arpida contacts:
Dr Khalid Islam, President and CEO Tel: + 41 61 417 96 60 Harry
Welten, MBA, CFO and Senior Vice Tel: + 41 61 417 96 65 President
Paul Verbraeken, Head of Corporate Tel: + 41 61 417 96 83
About Arpida Ltd.
Arpida (SWX: ARPN) is a biopharmaceutical company with research facilities near Basel, Switzerland and in the USA. It focuses on the discovery and development of novel drugs that seek to overcome the growing problem of microbial 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). The US Food and Drug Administration has granted fast track status to intravenous iclaprim. In July 2007, Arpida reported the completion of the Phase III programme in complicated skin and skin structure infections. An NDA filing is expected to take place in the second half of 2007. In June 2007, Arpida announced that it has received approval from the US FDA to initiate Phase II trials with intravenous iclaprim in the treatment of patients with hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or healthcare associated pneumonia (HCAP). An oral formulation of iclaprim has successfully completed three Phase I trials: an ADME study (absorption, distribution, metabolism and excretion) with radiolabelled compound, a Phase I bioavailability trial with a solution and one with a capsule formulation. 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 followed by outpatient treatment. This switch should be a valuable instrument in reducing healthcare costs and enhancing patient comfort. Arpida's fourth most advanced programme, AR-709, targets upper and lower respiratory tract infections acquired in the community setting. AR-709 exhibited potent activity against a large panel of pneumococcal clinical isolates including those resistant to currently used drugs. Promising results of "first-in-man" studies with AR-709 were published in March 2007. An additional compound, AR-2474, has achieved in vivo proof of concept. AR-2474 has been shown to be highly effective in eradicating pathogens 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 in 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. The views, expressed by Prof Bartlett do not constitute or imply endorsement by the Johns Hopkins University or the Johns Hopkins Hospital and Health System.
Posted: July 2007