Learning to Swallow a Bitter Pill - The Guardian (London) - August 22, 2001

Learning to Swallow a Bitter Pill: Baycol Fiasco Imperils Future of Drugs Group
By: Andrew Clark
The Guardian (London)
August 22, 2001

Bayer's chairman, Manfred Schneider, was enjoying some sun on the German holiday island of Sylt on August 6 when the pharmaceuticals company began the worst week in its history. The youthful 62-year-old, who has a passion for tennis, had retreated to the island for a break. Famous for its rolling sand dunes and its tolerance of nudism, Sylt is the German equivalent of the US resort Martha's Vineyard, with a big following among political and business leaders.

As events unfolded, Mr. Schneider admitted that he had allowed himself to be seduced by the island's charms: 'It would have been better if I had come back earlier.'

The mood was darkening 300 miles south at Bayer's Leverkusen head office. Regulators had become concerned about a spate of mysterious deaths in the US among patients taking Baycol (known as Lipobay in Britain), the anti-cholesterol drug which was considered the dynamo behind Bayer's earnings with expected sales of 1bn (pounds 633m) this year.

Late on the evening of August 7, Bayer executives contacted the Medicines Control Agency in London, which was handling Baycol's registration throughout the European Union. The message, delivered to the MCA's duty officer, was brief and direct: Bayer intended to withdraw the drug from the market the following morning.

Mr. Schneider, in touch with fellow directors by telephone, was sufficiently unconcerned to remain at his beachside retreat. On August 8, Bayer issued a brief statement recalling the drug, taken by 7m people worldwide, in the interests of 'patient safety'. The company was shocked by the savage reaction of the market: its shares plunged 18%, wiping 7bn off the firm's market capitalization.

Bayer executives complained that the financial markets were overreacting, pointing out that drugs were just one of four 'pillars', alongside chemicals, polymers and agriculture. The firm appeared rattled and wrong-footed by analysts' claims that the firm's pharmaceuticals business was too small to survive the blow.

Brilliant future At a hastily arranged press conference last week, a tanned Mr. Schneider faced his critics. The line from Bayer had changed: he described the withdrawal of Baycol as a disaster, admitting: 'Everything is certainly not all right in the Bayer world.'

Mr Schneider conceded that Bayer would consider giving up management control of its drugs business through a merger or joint venture. But he insisted Baycol's failure was mere bad luck. 'We simply assumed that we had an excellent blockbuster with a brilliant future. And the market was not telling us anything that could have caused us any doubts.'

Bayer has been sparing with its information, but it is gradually becoming clear how a single drug delivered such a shattering blow to one of Europe's biggest pharmaceuticals firms.

Launched in 1997, Baycol was marketed as a cut-price version of the cholesterol-lowering drugs which have come into vogue over the past 10 years. In Britain Baycol costs pounds 17.35 for a packet of 28 tablets at an average dose rate, compared to pounds 30 for Pfizer's Lipitor and pounds 29 for Pravachol, from Bristol-Myers Squibb.

Called statins, these drugs inhibit an enzyme in the liver which generates the kind of cholesterol that can clog up blood vessels. They are a crucial weapon in the battle against high blood pressure and heart disease, the biggest killer in most industrialized nations.

Doctors were initially reluctant to prescribe the new drug, on the basis that others had a longer track record of safety. But some complain that cost-conscious health authorities put pressure on them to use it, mindful of government targets to reduce heart disease. Graham Jackson, a cardiology specialist at Guy's and St Thomas's Hospital in London, says: 'Health authorities forced cerivastatin (Baycol) on to the market. Doctors didn't want it because there wasn't as much evidence that it was safe. The prescribing policy in certain areas was that 'this is the cheapest - you will prescribe cerivastatin'.'

Clinical trials of Baycol had thrown up a list of common complaints among people with high blood pressure such as flatulence, diarrhea, constipation and leg pains. But the incidence of these twinges was not significantly higher than among patients given a placebo.

It is common knowledge among doctors, however, that in very high doses statins can attack the muscles. In rare cases, this results in rhabdomyolysis, a serious condition in which muscle tissue breaks down into the blood, causing the failure of internal organs. Bayer advised doctors not to prescribe Baycol with another statin, gemfibrozil, to try to limit this risk.

The first death from rhabdomyolysis among Baycol patients was in the year of the drug's launch. But, as the drug was able to reduce hardening of the arteries by 80%, the risk-benefit ratio was considered sound. Bayer spokesman Gunter Forneck says: 'There are always risks in taking drugs - whenever you go under an anesthetic to have surgery, you have a risk of between 1% and 3% of death.'

A routine update on the number of side effects reported by doctors arrived at Bayer on June 15. This revealed that by the end of October 2000 doctors had reported 482 cases of rhabdomyolysis among Baycol users worldwide. In half of these cases, doctors had co-prescribed Baycol and gemfibrozil, sometimes because patients were diabetics, who needed more powerful cholesterol-lowering treatment. Dr. Jackson says: 'There is a benefit in co-prescribing the drug to diabetics. Diabetics are so hugely at risk of disease, it's amazing.'

When informed about the June update, the Medicines Control Agency wrote to doctors, reminding them not to prescribe Baycol with gemfibrozil, saying this combination increased the risk of serious side effects from 'between 1 in 1,000 and one in 10,000' to 'between 1 in 10 and 1 in 100 patients treated'.

The MCA appeared content to leave it at that, but the US food and drug administration was not. It demanded further talks with Baycol, citing 31 deaths in the US from the drug. Its concern has surprised some commentators: side effects from anti-impotence drug Viagra have killed 900 worldwide, compared with Baycol's running total of 52.

Industry sources suggest the FDA was prickly because the drug was co-promoted in America by GlaxoSmithKline, which had just been censured for failing to warn doctors adequately of the side effects of its diabetes drug Avandia.

Bayer maintains that no new information came to light between June and August, and its scientific experts spent this period sifting data and negotiating with the FDA.

The German firm insists that rhabdomyolysis is only a risk when the drug is prescribed to new patients is at its highest dose of 0.8mg, or when it is used with gemfibrozil. Lawyers representing patients in the US dispute this. Chicago lawyer Kenneth Moll has signed up several hundred alleged victims of side effects but says: 'I'm yet to find anyone who began on 0.8mg, or who took Baycol in conjunction with gemfibrozil.' He is suspicious of the delay between the June update and August decision to withdraw the drug: 'They knew about the deaths well before the recall and they delayed the recall.'

Dr Jackson is similarly sceptical: 'There is a feeling that there may be other trouble with the drug which we haven't heard about.'

Once one of the world's biggest drugs players, Bayer has slipped out of the top 10. The firm's pharmaceuticals arm is being stalked by larger rivals. The German firm, which discovered Aspirin, is in a critical condition. It has cancelled a Wall Street listing planned for next month. A 'strategic review' is under way, but Mr Schneider will need all his diplomatic skills to persuade investors that Bayer has an independent future in pharmaceuticals.