SOURCE: Basilea Pharmaceutica AG

December 30, 2009 01:34 ET

FDA issues ceftobiprole Complete Response Letter

BASEL, SWITZERLAND--(Marketwire - December 30, 2009) -

Basilea Pharmaceutica AG / FDA issues ceftobiprole Complete Response Letter processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement.

Basel, Switzerland, December 30, 2009 - 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. (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 Complete Response Letter to Johnson & Johnson PRD 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.

The FDA in its Complete Response Letter noted that, 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 to Johnson & Johnson PRD.

The FDA stated that given the number of clinical sites from which data are considered unreliable and/or unverifiable (10 of 49 clinical investigator sites audited by FDA or the third party auditor) and the types of monitoring inadequacies, including those that affect key safety and/or primary efficacy findings identified in the third party auditor reports, a favorable conclusion regarding data reliability at remaining clinical investigator sites cannot be reached.

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.

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 10 mL/min.

The Agency has indicated that it has not reviewed an amendment related to drug product specifications.

"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," said Dr. Anthony Man, CEO of Basilea Pharmaceutica.

Basilea is reviewing all strategic options to protect the interests of the company and its shareholders.

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.

Due to the deficiencies identified by the FDA in Johnson & Johnson PRD's conduct of the clinical investigations and Basilea's claimed breaches of the License Agreement, the company submitted a Request for Arbitration under the License Agreement for ceftobiprole in February 2009. Basilea's claims under arbitration include that Johnson & Johnson PRD breached the License Agreement by, among other things, causing the delay in the approval of ceftobiprole in the U.S. and EU. Basilea's initial significant damage claims, including milestone payments and additional damages, in the arbitration will increase as a result of this further delay.

In August 2009, the FDA issued to Johnson & Johnson PRD a Warning Letter on its role as a sponsor of clinical trials. The Agency noted that under the terms of the agreement between Basilea and Cilag GmbH International, a Johnson & Johnson company, all rights and responsibilities for ceftobiprole clinical trials were transferred to Johnson & Johnson PRD and the FDA concluded that Johnson & Johnson PRD did not adhere to the applicable statutory requirements or FDA regulations governing the conduct of clinical investigations. The FDA found numerous objectionable conditions during its investigation into Johnson & Johnson PRD's role as a sponsor of the two phase III trials of ceftobiprole for the treatment of cSSSI.

Basilea anticipates an arbitration decision prior to the end of 2010.

In February 2005, Cilag GmbH International, a Johnson & Johnson company, was granted an exclusive worldwide license to ceftobiprole. The NDA for ceftobiprole for the treatment of cSSSI was submitted to the FDA by Johnson & Johnson PRD in May 2007.

The FDA issued an Approvable Letter in March 2008. Thereafter, the Agency conducted additional inspections of the investigator sites and an inspection of the sponsor Johnson & Johnson PRD and issued a Form FDA 483 informing the company about the Agency's observations on Johnson & Johnson PRD's failure to ensure proper monitoring of the studies as well as deficiencies in study conduct.

In November 2008, the FDA indicated in its Complete Response Letter to Johnson & Johnson PRD the existence of data integrity issues and that further resolution of specific deficiencies of study conduct was necessary. The Agency also requested information on Johnson & Johnson PRD's clinical quality assurance programs.

Following a review of Johnson & Johnson PRD's response to the Form FDA 483, the FDA issued a Warning Letter to Johnson & Johnson PRD in August 2009.

In August 2009, the FDA accepted for review the Complete Response submission by Johnson & Johnson PRD to the ceftobiprole NDA for cSSSI. The Complete Response submission addresses the FDA Complete Response Letter issued in November 2008.

Ceftobiprole is an anti-MRSA broad-spectrum cephalosporin antibiotic. Ceftobiprole is marketed in Canada (ZEFTERA™) for the treatment of cSSSI, including non-limb threatening diabetic foot infections without concomitant osteomyelitis and in Switzerland (Zevtera™) for the treatment of cSSTI including diabetic foot infections without concomitant osteomyelitis. It is also approved in Russia, Azerbaijan, Ukraine and Hong Kong. Marketing applications for ceftobiprole are submitted in the EU and several other countries.

Conference call

Basilea Pharmaceutica Ltd. invites you to participate in a conference call on Wednesday, December 30, 2009, 2 p.m. (CET), during which the company will discuss today's press release.

Dial-in numbers are:
+41 (0) 91 610 56 00 (Europe and ROW)
+1 (1) 866 291 4166 (USA)
+44 (0) 207 107 0611(UK)

A playback will be available 1 hour after the conference call until Monday,
January 4, 2010, 6 p.m. (CET). Participants requesting a digital playback
may dial:
+41 (0) 91 612 4330(Europe)
+1 (1) 866 416 2558(USA)
+44 (0) 207 108 6233(UK)
and will be asked to enter the ID 11068 followed by the # sign.

About Basilea

Basilea Pharmaceutica Ltd. is headquartered in Basel, Switzerland, and listed on the SIX Swiss Exchange (SWISS: BSLN). Basilea's integrated research and development operations are currently focused on new antibacterial, antifungal and oncology agents to fight drug resistance and on the development of dermatology drugs. Basilea's products are targeted to satisfy high medical and patient needs in the hospital and specialty care setting.

The company owns a diversified portfolio including two commercialized drugs (Toctino®, ZEFTERA™/ Zevtera™ and one investigational drug (isavuconazole) in phase III clinical development. Toctino® (alitretinoin) is marketed in Denmark, France, Germany and the United Kingdom and is approved in Austria, Belgium, Canada, Finland, Luxemburg, the Netherlands, Spain and Switzerland. Toctino® has been recommended for approval in 16 European countries. Furthermore, a phase III clinical trial on alitretinoin for the treatment of severe chronic hand eczema is ongoing in the U.S.

Ceftobiprole is marketed in Canada under the brand name ZEFTERA™ and in Switzerland under Zevtera™. It is also approved in Russia, Azerbaijan, Ukraine and Hong Kong. Ceftobiprole is under regulatory review in the EU and several other countries. Basilea has set up commercial organizations in Canada, France, Germany, the Nordics and the United Kingdom, while it is building sales and marketing organizations in other countries to commercialize alitretinoin and to co-promote ceftobiprole, subject to approval.

Disclaimer

This communication expressly or implicitly contains certain forward-looking statements concerning Basilea Pharmaceutica Ltd. and its business. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd. is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.

For further information, please contact:
+---------------------------------+-------------------------------------+
|Media Relations                  |Investor Relations                   |
+---------------------------------+-------------------------------------+
|Adesh Kaul                       |Barbara Zink, Ph.D., MBA             |
|Head Public Relations &          |Head Corporate Development           |
|Corporate Communications         |                                     |
|+41 61 606 1460                  |+41 61 606 1233                      |
|media_relations@basilea.com      |investor_relations@basilea.com       |
+---------------------------------+-------------------------------------+

This press release can be downloaded from www.basilea.com

Press release (PDF): http://hugin.info/134390/R/1368719/334790.pdf

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