Protalix BioTherapeutics, Inc., announced that the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the company's New Drug Application (NDA) for taliglucerase alfa for the treatment of Gaucher disease.  Taliglucerase alfa is a plant-cell expressed form of glucocerebrosidase (GCD).  

A CRL is issued by the FDA's Center for Drug Evaluation and Research when the review of a file is completed and questions remain that preclude the approval of the NDA in its current form.

The main questions raised by the FDA regarding the NDA relate to clinical and chemistry, manufacturing and controls (CMC).  In the clinical section, the FDA requested additional data from the company's switchover trial and long-term extension trial.  At the time the NDA was submitted, full data from these trials was not available.  In the CMC section, the FDA requested information regarding testing specifications and assay validation.

"While we are disappointed by the receipt of the Complete Response Letter, we appreciate the FDA's efforts to complete the review of our NDA.  We noted that the FDA did not request additional clinical studies.  Moreover, the FDA inspected our manufacturing facilities finding them acceptable.  FDA also did not identify any issues in its audit of our clinical sites," said Dr. David Aviezer, the company's president and chief executive officer.  "Protalix will work with the FDA to determine next steps."

On November 30, 2009, Pfizer and Protalix BioTherapeutics, Inc. entered into an agreement to develop and commercialize taliglucerase alfa.

"Pfizer remains dedicated to the Gaucher community worldwide," said David Simmons, president and general manager, Emerging Markets and Established Products Business Units, Pfizer Inc.  "We will work closely with Protalix to address the requests from the FDA in a timely manner by providing technical, analytical and regulatory expertise."

Protalix will request a meeting with the FDA as soon as possible to clarify the path to regulatory approval.

Patient enrollment remains open in Protalix's multi-center, double-blind pediatric trial of taliglucerase alfa. Patients currently enrolled in the switchover study and extension study will continue to receive the drug.  In addition, taliglucerase alfa is currently being provided to Gaucher patients in the US under an Expanded Access protocol, under special access agreements such as in France and Brazil, as well as to patients in the rest of the world under Named Patient provisions.  

Protalix is a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell based expression system, ProCellEx.