Exanta's risk/benefit conundrum revealed

Two studies in the Journal of the American Medical Association place ximelagatran (Exanta; AstraZeneca) in the spotlight again for the first time since the FDA rejected approval of the thrombin inhibitor. The studies report the two Phase III trials, which showed that Exanta was as effective as warfarin and low-molecular-weight heparin for deep vein thrombosis and stroke prevention in atrial fibrillation. However, both studies raised questions about liver toxicity, and one trial raised suspicion of increased coronary events. A third article in the journal shows that Exanta is cost-effective only for patients with a high risk of intracranial haemorrhage or a low quality of life while taking warfarin. In an editorial accompanying the papers, Victor Gurewich from the Beth Israel Deaconess Hospital Medical Center, Boston, says the benefits of Exanta over warfarin, a drug that is notoriously difficult to manage and has adverse reactions with a number of other treatments, need to be considered. Gurewich suggests that the definition of these risks can be achieved only through post-marketing surveillance, not in a clinical trial. http://jama.ama-assn.org/

Crawford nominated for permanent FDA commissioner post

The FDA's Acting Commissioner, Lester Crawford, has been nominated for the full-time post by President Bush. Although many are relieved that a permanent commissioner has been nominated, critics are disappointed that an outsider wasn't chosen, particularly in light of recent controversies about drug safety and the agency's relationship with drug companies. The FDA announced that it was creating a new independent Drug Safety Oversight Board to monitor approved medicines once on the market and to update physicians and patients with new information on risks and benefits. Full details were not released at the time of going to press, but Crawford said that the board would be made up of scientists throughout the federal government that will advise the FDA, although it will not have the independent power to force the withdrawal of drugs.

Pfizer to cut sales jobs?

A Lehman Brothers analyst has written in a research-note estimate that Pfizer could lay off up to 30% of its 38,000-member sales and marketing staff. A large-scale redundancy of as many as 11,000 sales reps would lower Pfizer's costs by US$1.5 billion to $1.7 billion a year and increase annual earnings by an estimated 17 cents a share, says C. Anthony Butler. Pfizer confirmed that it is looking at measures to streamline its business, but will provide details of the plan at a meeting with analysts in early April. Pfizer shares rose 2.6% to US$25.55 in response to the suggestions of job cuts.

HIV generic approved amongst a new climate of fear

South Africa's largest pharmaceutical company, Aspen Pharmacare, has become the first to receive approval from the FDA for the manufacture of a generic antiretroviral regimen containing lamivudine/ zidovudine and nevirapine for the treatment of HIV/AIDS. Patents for lamivudine/zidovudine and nevirapine still belong to the original innovator companies, and the approval of this regimen is 'tentative', meaning that it cannot be marketed in the US, but it does meet the agency's standards for safety and bio-equivalence. The treatment will be available for use under the President's Emergency Plan for AIDS Relief, a 5-year global strategy. Meanwhile, New York City health officials announced that a man in New York has been infected with a highly virulent form of the HIV virus that is resistant to three of the four classes of anti-HIV drugs. Analysis by two independent labs confirmed that this form of the virus infects cells through CX4 cellular receptors, which are typically found only in those infected with HIV for a long time and in advanced stages of AIDS.

Adderall risks create difference in opinion

Health Canada have suspended sales of Adderall XR (Shire) for attention deficit hyperactivity disorder (ADHD) in light of reports that since 1994 the drug has been linked to 20 sudden deaths and 12 strokes. The FDA, however, said it had evaluated the same reports as Health Canada, yet believed that the data warranted an additional warning stating that Adderall XR should not be prescribed for people with structural cardiovascular abnormalities. Health Canada said it is asking manufacturers of related treatments for ADHD to provide a thorough review of their worldwide safety data.

Agreement reached over cancer vaccines

GlaxoSmithKline has said it will receive an upfront payment and unspecified royalties from Merck after settling a patent dispute with Merck concerning both of its cervical cancer vaccines. The agreement allows both companies to introduce their potential blockbuster human papillomavirus vaccines during the next couple of years, but GSK will get a share of Merck's revenues, estimated to be between 5–7% of global sales. Merck plans to file its vaccine for regulatory approval with the FDA in the second half of 2005, and GSK expects to file its vaccine for approval in Europe in 2006.