Glaxo faces storm over Seroxat

CLINICAL auditors from Britain's medicines control agency are expected to descend on Glaxo-SmithKline this week amid concerns that the pharmaceuticals group may have suppressed a series of negative studies on its key antidepressant drug Seroxat, known as Paxil in the US.

In a highly unusual move, a team from the Good Clinical Practice unit of the Medicines and Healthcare Products Regulatory Agency (MHRA) will demand access to all of GSK's files and studies on Seroxat.

The decision to take this dramatic step was taken following the delivery to the MHRA of nine studies of Seroxat that confirm the antidepressant can lead to suicidal tendencies and other medical damage when administered to people under the age of 18.

There has been extensive media coverage of the potential harmful effects on young people of Seroxat, one of GSK's leading compounds. But until now the company has declined to acknowledge any serious problems.

This week, however, it will be asked by the MHRA to contact general practitioners, letting them know of the potential dangers to people under 18.

Sources at GSK confirmed that an amendment to the instructions carried with Seroxat was under discussion with the authorities and an announcement would be made shortly. There was no knowledge of the impending clinical audit.

Disclosure of the regulatory concerns about Seroxat, which contributes £1.5bn-£2bn of annual turnover to GSK, is likely to lead to nervous selling on the stock market when it opens for business today. Glaxo shares have recovered to 1258p this year after falling below £10 in 2002.

Concerns that clinical practices may have slipped at Britain's flagship pharmaceuticals group will put additional pressure on the company's chief executive Jean-Pierre Garnier, who is already under fire over his possible £22m severance package.

A senior source at the MHRA told the Daily Mail that the decision to conduct an audit at GSK was 'very, very unusual'. 'Normally we have a good relationship with these guys and work closely together,' the source said.

If it were found that critical studies had not been available to regulators then GSK could eventually face criminal charges under the Medicines Act.

Previous Good Clinical Practice audits have been carried out at second-line pharmaceutical groups where research practices are sometimes less rigorous.

Members of the Committee on the Safety of Medicines, the licensing arm of the MHRA, were disturbed when they saw the parallel Seroxat and placebo studies recently submitted by GSK. They revealed a predilection to suicide, aggressive behaviour and other psychosis in Seroxat users under 18, which were not present in the placebo studies.

The belief is that a deep volume of research work showing 'contraindications in children' could not have been carried out overnight and the appropriate regulatory authorities should have been alerted much earlier - so appropriate amendments could be made.

The big worry for GSK now is that the disclosure of the disquiet at the MHRA and its offshoots could attract the attention of the Food & Drugs Administration in the US, which works closely with the British regulators.

That could seriously damage GSK's reputation in the US, where it does much of its business and where Garnier has his headquarters.

A spokesman for GSK said: 'We can confirm we are in discussion with the MHRA regarding proposed updates of the product characteristics of Seroxat. However, it is not appropriate to discuss this dialogue further until the outcome of this review.

'Seroxat is an important medication for treatment of anxiety and depression, and has been for more than 10 years. It has benefited the lives of millions of people suffering with these serious conditions.'

A decision on the safety of Seroxat/Paxil, and other widely prescribed anti-depressants like Eli Lilly & Co's Prozac, will be announced tomorrow, according to the UK Medicines Control Agency. 'We will be making an announcement about Seroxat tomorrow but we're not saying anything in advance,' spokeswoman Alison Langley said.

Glaxo refused to comment on whether a clinical audit was being carried out, but confirmed it is in talks with the MHRA. 'We can confirm we are in discussion with the MHRA regarding proposed updates of the product characteristics of Seroxat,' Glaxo's Martin Sutton said.

SEROXAT is one of the biggest selling antidepressants in the world. It treats depression, panic, obsessive compulsive disorder, post-traumatic stress disorder, social anxiety disorder and general anxiety disorder. Last year 400,000 people were prescribed the treatment, also known as the 'anti-shyness pill', in Britain alone.