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."
Results ASSIST-2
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
Communications
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
