FDA Issues Complete Response Letter To Johnson & Johnson PRD For Ceftobiprole

Basilea Pharmaceutica has reported that the FDA has issued to the sponsor, Johnson & Johnson Pharmaceutical Research and Development (Johnson & Johnson PRD), a Complete Response Letter on Ceftobiprole for the treatment of complicated skin and skin structure infections (cSSSI).

The FDA has indicated in its letter that it has completed the review of the application and has determined that it cannot approve the application in its present form.

The Agency determined that data from studies BAP00154 and BAP00414 cannot be relied upon because inspections and audits of approximately one-third of the clinical trial sites for these studies found the data from a large proportion of these sites to be unreliable or unverifiable, raising concerns regarding the overall data integrity for both studies.

In addition, the FDA’s Division of Scientific Investigations (DSI) determined that Johnson & Johnson PRD failed to adequately monitor the clinical investigators’ conduct of these studies, as outlined in its Warning Letter issued earlier this year.

The FDA also requested further information related to the justification of the non-inferiority margin for two patient subsets with abscess following primary incision and drainage or diabetic foot infections.

In order to address the deficiencies, the Agency recommends that two new, adequate, and well-controlled studies to evaluate the safety and efficacy of ceftobiprole for the treatment of cSSSI should be conducted.

Additionally, the Agency recommends a meeting of the sponsor Johnson & Johnson PRD with the Division of Anti-Infective and Ophthalmology Products to discuss the design of the efficacy and safety parameters of these trials, including an evaluation of any seizure or hyponatremia events. Although not a deficiency, the Agency requests a clinical pharmacology study for patients with a creatinine clearance less than 10ml/min.

Anthony Man, CEO of Basilea, said: “There is a huge medical need to fight potentially deadly resistant bacterial infections. We are clearly disappointed with this further delay due to study conduct issues outlined by the FDA. We are committed to make Ceftobiprole more widely available to patients as quickly as possible.”

The regulatory review of Ceftobiprole for the treatment of complicated skin and soft tissue infections (cSSTI) in the EU is on-going. An opinion by the EU Committee for Medicinal Products for Human Use (CHMP) is anticipated in Q1 2010. Basilea anticipates an arbitration decision prior to the end of 2010.