Baycol Journey and Downfall of Baycol

BAYCOL’S JOURNEY AND DOWNFALL OF BAYER:

BAYER’s Transition

In 1863, a German company “Bayer” founded by Friedrich Bayer and Johann Friedrich Weskottr. Since then, it has faced various up and down (Themistocleous 2000). During 1980’s, Bayer’s pharma ranked 2nd in the world, which has been pushed down to 16th place in 1999 due to impact by Baycol withdrawal. Bayer’s stubbornness & low shares market value let the company sink despite an extreme need of merger.

War of the Statins

Statins are the anticholesterol drug which lowers the bad LDL cholesterol. Anticholesterol that includes statins has been considered as one of the fastest growing and profitable drug category. After the arrival of first statin (lovastatin) by Merck & Co’s Mevacor, the pharmaceutical market was bombarded with various brands of statin drug by different pharma ventures.

Lovastatin in 1987, Merck & Co’s Mevacor[pic 1]

Simvastatin (Zocor) in 1988 Merck & Co’s Mevacor

[pic 2]

Pravastatin (Pravachol) in 1991 by Bristol-Myers Squibb’s

[pic 3]

Fluvastatin (Lescol) in 1994 by Novartis Pharmaceuticals.[pic 4]

Lipitor in February, 1997 developed by Warner-Lambert and Pfizer.[pic 5]

Cerivastatin (Baycol) in April, 1997 by Bayer Pharmaceuticals.

[pic 6]

A Dent in Statins Success

It has been established that statins produce the adverse effect rhabdomyolysis, a condition of muscle weakness (myopathy) with creatinine kinase (CK) level more than 10 times of upper limit of normal (CK>10X ULN) and compromised renal function. Rhabdomyolysis is related to the dose of statins and generally higher doses increase the risk, also the use of statins in combination with certain drugs especially the fibrate gemfibrozil (Chong, Seeger, & Franklin, 2001; Rosenson, 2004). However, there were few reports of incidence of rhabdomyolysis due to statins during the clinical trial (up to 0.5%) before “Baycol’s” introduction. Also, the inclusion criteria were restrictive during trials of statins to detect serious adverse effects. So the statin-associated rhabdomyolysis appears after marketing.

BAYCOL Drug Development and Issues:

Baycol (Statin) was a potent anticholesterol drug, therefore the toxicologist during a meeting in 1991 for IND (Investigational New Drug Application) insist that 0.4 mg is the highest possible dose for Baycol as the dose-response curve is steeper, and there are high chances of dose associated adverse effects.

Bayol’s initial maximum approved dose was ≤0.3 mg with no increment in CK level, and possess dual elimination mechanism, so considered safe as per stipulation of a toxicologist. However, the Baycol’s possess limited LDL cholesterol efficacy, which is lower as compared to Lipitor. Bayer’s later decides to undergo clinical trial for 0.4 mg, 0.8 mg and 1.6 mg to compete with Lipitor.  Other Pharma industries like Merck, also get involved in this high drug selling competition. After the launch of Baycol, the post-marketing reports started to show rhabdomyolysis cases, alike other statins which are tried to rectify by Bayer by filing contraindication label for concurrent use of Baycol and gemfibrozil in the US.

A Beginning of BAYCOL’S Crisis:

In 1999, Baycol’s 0.4 mg get approval and quickly became the US most prescribed drug. Soon after that, the clinical trials for 1.6 mg revealed a high rate of enhanced CK level, whose results were not published. The issue with Baycol was again discussed in the internal meeting that suggests the risk of rhabdomyolysis due to Baycol, which is 10 times higher than other statins. In another hand, the reports of rhabdomyolysis continue to appear due to concomitant use with gemfibrozil, So the solution suggested to be inserted patient package which was suspended until July 2000 to not further delay the approval of 0.8 mg Baycol.

In 2000, 0.8 mg Baycol get FDA approval despite concerns due to increased CK levels that are highest 2.1 percent as compared to 0.9 percent of Lipitor (80mg). Soon after that, the Bayer submitted an application in the US for approval of patient package insert to avoid concomitant use of gemfibrozil and Baycol. However, the EU prescribing information have merely carried the original general precautions and warning, and the company avoided the changes as it may delay the 0.8 mg Baycol introduction in other countries.

In June 2000, a report published by Bayer about Baycol’s association with myopathy. A similar clinical study could have been performed earlier, but was not conducted because of partial confidence on Baycol’s efficacy and lack of interest by stakeholders. Nonetheless, the Baycol’s safety assurance matter soon becomes uninteresting (Angelmar, 2007).

Bayer does not possess any crisis management policy, also they possess some data that linked Baycol use with gemfibrozil might cause a fatality but they did not follow up with further testing due to lack of enthusiasm ("Bayer Corp. Restructuring assists recovery," 2010). An extensive test of Baycol should be conducted rather than the assumption that drug effectiveness may outweigh the risks. A lack of ability to take action resulted in Bayer’s downfall.

Moreover, after acquiring the information related to Baycol’s adverse effects the company did not inform the patients first, instead stockholders were well informed. The prioritization of investors over patients downgraded the image of the company further, so the FDA stepped forward and expressed the dissatisfaction (Angelmar, 2007).

Between 2000 to 2001, 18 fatality cases reported due to Baycol in the U.S. A meeting among drug safety stakeholders analyzed that most of the fatalities were due to the use of 0.8 mg Baycol alone, and only 1 case was associated with concomitant use of gemfibrozil. As per FDA instructions, Baycol’s prescribing information updated and 0.4 mg preferred as starting dose in the US. However, the act to lower the dosages in the United States appears responsible, but they should have postponed the release of 0.8 mg dosage in the UK and other countries, or at least perform scrutiny on Baycol to prevent issues in the international market (Alperowicz, 2003). This lack of research and initiation of action soon resulted in disaster. Finally, after the voices regarding rhabdomyolysis associated fatalities due to Baycol in different countries, Bayer withdraw Baycol from all market in 2001.