The FDA appointed advisory committee on whether to recommend approval for Dendreon’s Provenge (sipuleucel-T) met in Washington, D. C. on March 29th. After voting unanimously to recommend Provenge as “reasonably safe,” the 17-member panel fell short of unanimity on whether the drug is effective. The first 4 votes were against. Following intervention by an FDA official, 13 members voted in favor. Accounts vary as to how and why the FDA official intervened during the vote.

Dendreon’s Provenge vaccine now awaits the F. D. A.’s decision following the advisory panel hearing in Washington D. C. March 29.

Provenge is intended as the first treatment of its kind to stimulate a patient’s own immune system against prostate cancer. If it’s approved, analysts say it could generate up to $1 billion in annual sales.

Provenge is made for each individual patient. Scientists take the patient’s own white blood cells, mix them with a genetically engineered protein and reintroduce them into the patient. Specifically, blood is drawn from the patient and dendritic cells are extracted from the blood and loaded in the laboratory with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor (GMCSF). This product is infused into the source patient at repeatable intervals; during trials, patients received uo to 3 infusions of vaccine.

In two studies, as we reported March 28 in covering F. D. A.’s questions to its advisory panel, the company failed to demonstrate the product could slow the

Erythropoietins (Epo agents) widely sold and prescribed as anemia-fighting drugs that can help cancer patients avoid blood transfusions may worsen the health of some cancer patients and even hasten death.

FDA announced that Amgen Inc. and Johnson & Johnson (J&J) would add strong new “black box” warnings to their anemia drugs Procrit, Epogen, and Aranesp after several recent studies showed a higher risk of death and life-threatening side effects in some patients.

F.D.A. is re-evaluating the validity of claims in the labels and in advertisements that the drugs can raise energy levels or otherwise improve a patient’s quality of life.patients.

Tom Lamb at drugwatch.com says FDA has cancelled plans that they announced in 2005 to establish a new web site, to be called Drug Watch, that would alert doctors and patients about emerging drug safety issues. “One could think of it as the FDA’s early-warning system for serious side effects that might be linked to FDA-approved prescription drugs,” Lamb says.
This new Drug Watch web site, Lamb says, was supposed to be “a key part of the FDA’s effort to improve its performance in fulfilling its drug safety monitoring role, which was roundly criticized following the September 2004 Vioxx recall.”

Trovax vaccine is designed to deliver a proprietary tumor associated antigen, 5T4, to a broad range of solid tumors. The vaccine is designed to use a pox virus vector, modified vaccinia virus Ankara (MVA).

In today’s deal, Sanofi-Aventis agrees to pay British biotech company Oxford BioMedica $690 million licensing fees for TroVax. Sanofi pays $39 million up front and $25 million installments. Sanofi will pay more if Trovax is approved to treat multiple cancers.

Clinical trials of Trovax vaccine include a small Phase II trial for prostate cancer, which began in Texas in 2006. This trial was designed for:

* Hormone-refractory prostate cancer
* TroVax administered either as a single agent or in combination with GM-CSF
* Recruitment was completed in July 2006
* To date 85% of patients treated with TroVax mounted an immune response

This Phase II trial in prostate cancer ran at the Methodist Hospital in Houston with Dr Robert Amato as principal investigator. The trial was designed to enroll 24 men with hormone-refractory prostate cancer who had previously received chemotherapy or had refused chemotherapy and had progressive disease. The trial was open label with two arms (12 patients each) to assess the activity of TroVax alone versus TroVax alongside an approved treatment for prostate cancer, granulocyte macrophage-colony stimulating factor (GM-CSF).

Sanofi-aventis and Oxford BioMedica Enter Global Licensing Agreement to Develop and Commercialise TroVax For Cancer

PARIS, March 28, 2007 – Sanofi-aventis and Oxford BioMedica announced today that they have entered into an exclusive global license agreement to develop and commercialise TroVax® for the treatment and prevention of cancers.

TroVax® is Oxford BioMedica’s lead cancer immunotherapy. This therapeutic vaccine has been evaluated in clinical trials involving more than 180 patients with various forms of cancer. A Phase III trial – called TRIST – in renal cancer is ongoing.

Federal drug regulators on Tuesday released briefing documents that pose questions about the effectiveness of Provenge (sipuleucel-T), Seattle-based Dendreon Corp.’s experimental prostate cancer vaccine. On Thursday March 29 the Cell Tissue and Gene Therapy Committee (CTGT) will accept submissions from interested parties. The committee will then review the drug and recommend to the FDA that it be approved – or not be approved.

Prostate cancer advocates, acutely aware of the paucity of treatments available for men with hormone refractory prostate cancer, plan to attend the meeting to lobby for acceptance of Provenge.

The FDA committee’s questions pinpoint drug stability, efficacy and safety. A slightly higher rate of adverse events including explained and “unexplained” death (see below) occurred in men who took the vaccine.

FDA’s decision will be based on results of randomized trials, which tested Provenge against placebo (for which a dummy vaccination procedure was used). However, a subset of patients received Taxotere when their cancer progressed — either after Provenge, or after placebo or after placebo followed by a course of frozen-stored vaccine.