Monitoring Issues Cause Drug Delay

FDA issues Complete Response Letter for ceftobiprole

Basel, Switzerland, November 26, 2008
Basilea Pharmaceutica Ltd. announces that the U.S. Food and Drug Administration (FDA) issued to the sponsor, Johnson & Johnson Pharmaceutical Research and Development, L.L.C. (J&JPRD), a Complete Response Letter for ceftobiprole for the treatment of complicated skin and skin structure infections including diabetic foot infections.

Ceftobiprole showed in two large multinational, double-blind, randomized phase III clinical studies, that it was effective, as demonstrated by meeting the primary endpoint using a 10% non-inferiority margin. A safety profile consistent with the cephalosporin class of antibiotics was demonstrated. Ceftobiprole has been approved or recommended for approval in a number of territories including the European Union.

The FDA indicated in a Complete Response Letter to J&JPRD that further resolution of specific deficiencies of study conduct is necessary. As a result of FDA audits at investigator sites and of the sponsor J&JPRD, the Agency suggested that J&JPRD have additional clinical site audits performed.

The FDA indicated from their sponsor/monitor inspection that there was a failure to ensure proper monitoring of the studies. The Agency has requested information on J&JPRD's clinical quality assurance programs and also asked for a new audit plan that also addresses deficiencies in contract research organization monitoring. The FDA indicated to J&JPRD that they are unable to review the clinical data included in the submitted complete response until issues of data integrity have been resolved. The FDA has indicated to J&JPRD the need to fully respond to this action letter within one year.

"Ceftobiprole is a novel antibiotic addressing the very serious medical need related to resistant bacterial infections including MRSA. The drug met its primary clinical endpoint and was approved or recommended for approval in a number of countries including the EU based on two large independent and well designed trials. We are deeply disappointed with the further delay in the review of the U.S. NDA application. We will be working with J&JPRD and the FDA to address these outstanding issues as soon as possible. These events have not altered in any way our confidence in the efficacy and safety profile of ceftobiprole and its potential to satisfy a high medical need", said Dr. Anthony Man, Basilea's CEO.

The NDA submission of ceftobiprole for the treatment of complicated skin and skin structure infections includes the data from two pivotal phase III trials (STRAUSS 1 and STRAUSS 2). These trials comprise data from over 1600 patients including those with diabetic foot infections caused by Gram-negative and Gram-positive pathogens and with methicillin-resistant Staphylococcus aureus (MRSA) infections. In both of these large, multinational, double-blind, randomized phase III clinical studies, ceftobiprole was effective as demonstrated by achievement of the non-inferiority endpoint to single drug or two-drug combination comparators, respectively.

The New Drug Application (NDA) was submitted to the FDA by Johnson & Johnson Pharmaceutical Research and Development, L.L.C. The FDA issued an Approvable Letter in March, 2008. The questions in the Approvable Letter were addressed in a complete response package that was filed and accepted by the FDA for review in September 2008.

Ceftobiprole is marketed in Canada and approved in Switzerland. Ceftobiprole received a positive opinion from the CHMP in the European Union in November 2008 and is under review in a number of other countries.