Merck & Co (trading in Europe as MSD) has agreed to pay almost a billion dollars to settle criminal and civil claims relating to its US promotion of the arthritis drug Vioxx.

The total of $950m covers all outstanding cases in the US relating to the drug’s off-label marketing and alleged false statements regarding its safety.

Ironically, Merck’s anti-inflammatory drug has perhaps inflamed more legal trouble than any drug in recent history.

Launched in 1999, Vioxx (rofecoxib) was used worldwide for treatment of rheumatoid arthritis. Merck withdrew it from the global market in 2004, responding to evidence that it increased the risk of blood clotting and other serious cardiovascular events.

However, as early as September 2001, the FDA had sent Merck a Warning Letter directing the company to cease publishing marketing materials which it judged to be “false, lacking in fair balance, or otherwise misleading”.

The criminal charges against Merck in the USA relate to its promotion of Vioxx as a treatment for rheumatoid arthritis for three years without FDA approval. The drug was finally approved by them in that indication in 2002.

The civil charges in the USA have taken the form of thousands of private lawsuits by patients or their relatives, claiming that Merck marketed the drug in an off-label indication and/or that it made false statements to Medicaid regarding the drug’s risks.

Class actions on behalf of thousands of patients have been launched in the UK and Australia.

Merck made approximately $11bn in global revenue from Vioxx, but stands to lose most of that. The company has already paid $4.85bn to settle individual lawsuits and almost $2bn in legal costs.

Under the terms of a plea agreement with the US Department of Justice, Merck will plead guilty to a single misdemeanour for its promotion of Vioxx in the US between 199 and 2002, paying a $322m fine.

The company will settle all US civil claims with a $628m payment that covers both the off-label marketing and the claims of misleading statements. Of this payment, two-thirds will be recovered by the US Government and the rest by Medicaid.

Merck & Co commented that the civil settlement did not constitute any admission of liability or wrongdoing at the corporate level: “As part of the plea agreement, the US acknowledged that there was no basis for a finding of high-level management participation in the violation.”

The case reflects the issues facing global pharma companies concerning potential breaches of regulations by executives at lower levels.

The most dramatic allegation regarding Vioxx has come from Australia, where a court heard in 2009 that doctors had received a bogus ‘clinical research journal’ containing pro-Vioxx articles credited to non-existent doctors and written by Merck’s marketing team.

The FDA has again extended the indication for Erbitux (cetuximab) and approved the treatment for patients with advanced head and neck cancers in combination with chemotherapy.

The extension is based on the EXTREME study of 442 patients previously untreated with chemotherapy that demonstrated those treated with Erbitux lived 10.1 months on average, compared with 7.4 months on those treated with chemotherapy alone.

Richard Pazdur, Head of Oncology, FDA, says the medication is an “important tool” for doctors and patients.

Erbitux is now approved for five separate indications across two tumour types and becomes the first regimen in 30 years with extended overall survival in patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck to be approved.

CorMatrix Cardiovascular, developer of extracellular matrix (ECM) biomaterial devices, has received FDA approval for its CorMatrix ECM device.

The indication for use in the US relates to the vascular reconstruction and repair of the carotid artery, including patch closure following endarterectomy and suture line buttressing.

David Camp, Chairman & CEO of CorMatrix, said: “We believe the unique properties of our CorMatrix material provide a new and vital alternative to current approaches in carotid artery repair.”

The device utilises CorMatrix’s ECM technology to provide a natural bio-scaffold to enable adjacent tissues to deliver cells and nutrients to the matrix, which then differentiate into tissue-specific cells, ending in the repopulation and repair of damaged tissue.

The company currently has US and European approval for its ECM technology as an implant for pericardial closure and for use in cardiac tissue repair.

Based in Atlanta, Georgia, CorMatrix Cardiovascular both develops and delivers cardiovascular devices that harness the body’s ability to repair damaged tissue.

Eli Lilly has received a positive opinion from the CHMP for Alimta as continuation maintenance therapy of advanced nonsquamous non-small cell lung cancer (NSCLC).

The recommendation is for the pemetrexed injection to be used as part of maintenance therapy, a relatively new concept in lung cancer treatment to commence immediately after patients have completed first-line treatment, in an effort to sustain disease control.

Dr Allen Melemed, Senior Medical Director of Alimta at Lilly Oncology, said: “Lung cancer is one of the most difficult cancers to treat and new therapy options are much needed.”

The CHMP’s recommendation will be reviewed by the European Commission, which will decide whether to approve the treatment for indication in Europe.

Dr Melemed commented: “If approved, Alimta would be the first tailored treatment option based on efficacy that can potentially extend lives beginning in first-line treatment and continuing through maintenance in advanced nonsquamous non-small cell lung cancer.”

No chemotherapy is currently approved as ‘continuation maintenance’ treatment. Currently approved lung cancer maintenance therapies use different medicines in the first-line and maintenance phases of treatment.

The CHMP's opinion was based on clinical research results from Paramount, a randomised, double-blind Phase III study involving patients with advanced nonsquamous NSCLC. Participants received initial therapy with four cycles of Alimta plus cisplatin. Patients whose disease did not progress continued to the maintenance phase, where survival was assessed in patients who received Alimta plus best supportive care (BSC), compared with those who received a placebo plus BSC.

Alimta is already approved in the first-line, maintenance and second-line settings in the EU and US for the indication. The treatment was originally recommended by NICE in September 2009 to treat the cancer on the NHS in the UK, but reversed its decision in December 2009, citing data uncertainties. NICE came to a final recommendation in June 2010.

Lung cancer is the most common form of cancer in the world, causing 1.3 million cancer deaths each year. NSCLC contributes to 85-90% of all lung cancers.

Roche has pitched a “middle-ground proposal” to the FDA in the hope of salvaging the use of Avastin only with paclitaxel for the treatment of breast cancer.

The compromise comes weeks after the FDA advisory committee voted in favour of pulling the indication after citing that clinical studies that did not indicate results of prolonged survival or slowing disease progression.

The new proposal includes revised labelling, which would recommend the medicine to those showing “aggressive disease” have few other treatment options available.

Roche also suggests a Risk Evaluation and Mitigation Strategy (REMS) and a Medication Guide to accompany the medicine.

The Swiss-based company is estimated to lose $1bn in annual sales if the FDA removes Avastin’s indication.

Despite the FDA’s opinion, The National Cancer Comprehensive Network has maintained its endorsement of the drug, with Medicare also likely to continue its use in the US.