Baycol Timeline -- Key Events in the History of the Recalled Cholesterol Drug Baycol.
CORPUS CHRISTI, TX -- (INTERNET WIRE) -- 03/13/2003 -- Emails, memos and other documents made public in a Corpus Christi, Texas, courtroom give a dramatic behind-the-scenes look at Bayer Corporation's response to reports of injuries and deaths related to its cholesterol drug Baycol. The following timeline, taken from news accounts and some of the trial exhibits, lists some of the key events and facts leading up to the drug's recall.
June 26, 1997: The U.S. Food and Drug Administration (FDA) approves a 0.3-milligram (mg) dose of Baycol.
June 27, 1997: In a letter from Jerry Karabalas, executive vice president for pharmaceuticals at SmithKline Beecham, Bayer's marketing partner for Baycol, to David Ebsworth, president of Bayer's North American pharmaceutical operations, Karabalas expresses serious concerns in regard to Baycol. He states that Baycol, although costing less than its competitors, shows problems with drug interactions that are magnified at higher doses. "Simple and safe no longer appears to be a viable promotional platform," he says.
Feb. 3, 1998: An amendment to a co-promotion agreement between Bayer and SmithKline Beecham Corporation sets out two $4 million "milestone" payments from SmithKline to Bayer. The first would be paid following initiation of a study on Baycol 0.8 mg and the second after 1,000 patients had received Baycol 0.8 mg for six months.
May 28, 1998: A post-marketing report by Bayer shows that four cases of rhabdomyolysis ("rhabdo") have been reported from patients receiving the 0.3 mg dose.
May 31, 1998: A document sent to David Ebsworth, president of Bayer, says the company needs to do everything it can to maximize the sale of Baycol because it must carry the company for the short and long haul.
April 1, 1999: A Bayer document reports that the company has received 29 adverse event reports as of March 1999. This is before the Baycol 0.4 mg dose goes on the market.
April 23, 1999: An email from Roger Celesk, a Bayer Corp. executive (Deposition Exhibit 140) states that Bayer's safety department has received 31 U.S. reports and 21 non U.S. reports of rhabdo associated with Baycol. An additional seven cases were identified in the FDA's report listing.
May 5, 1999: In an email regarding Baycol safety labeling it is recommended that Baycol not submit certain negative information to labeling at this time unless they hear otherwise from another Bayer Corp. official. This comes just prior to Bayer receiving permission from the FDA to approve a 0.4 mg dose of Baycol, which would trigger a $5 million payment to Baycol from SmithKline.
May 24, 1999: The FDA approves a 0.4 mg dose of Baycol.
Oct. 1, 1999: An interoffice memo in regard to Dr. Evan Stein, a clinical investigator and consultant for Bayer, states: "Dr. Stein has been quite vocal about the lack of candor in presenting our safety level."
Oct. 19, 1999: Roger Celesk in an email to Franz Hulla
(Deposition Exhibit 139) reports that a physician in
Texas reported rhabdomyolysis cases in two patients
who were switched from fluvastatin to cerivastatin (the
generic name for Baycol). The patients, who were hospitalized,
developed rhabdo within a month. Celesk reports that
follow-up research on his part uncovered a third case
in California. All three cases involved the use of 0.4
mg cerivastatin plus gemfibrozil, another drug marketed
under the name of Lopid.
Oct. 25, 1999: An FDA warning letter is sent to Bayer stating that its promotional material is "false, lacking in fair balance, or otherwise misleading" for overstating its efficacy and for understating the risk of rhabdomyolysis.
December 1999: Bayer adds a warning to its label stating that Baycol should not be prescribed with Lopid (gemfibrozil).
Dec. 30, 1999: In a memorandum from an unknown Bayer executive to E. Paul MacCarthy and Lawrence Posner, senior vice president for pharmaceutical development, it is reported that 60 cases of rhabdo had been received in the company's safety assurance department. "The steadily increasing numbers of spontaneous reports of rhabdomyolysis associated with Baycol, along with the additional telephone activity, has overwhelmed the available Safety Assurance resources in terms of processing SAEs," the memo states.
March 10, 2000: An email from Steve Niemcryk, an epidemiologist and a member of Bayer's drug safety surveillance group, to Richard Goodstein, vice president for scientific relations at Bayer, discusses the relationship between Baycol 0.8 mg dose and rhabdo and compared the frequency to other statin drugs. Using an FDA database, Niemcryk states that Baycol caused patients to come down with rhabdo five times more often than Mevacor, 10 times more often than Lipitor and Lescol, 20 times more often than Zocor and 67 times more often than Lipostat.
May 13, 2000: In an email (Exhibit 428), Dr. Richard Goodstein, vice president for scientific relations at Bayer, tells a colleague: "I see a false comfort factor in place across the company for obvious reasons. It appears the strategy is to get by that July hurdle (a meeting with the FDA to obtain approval of 0.8 mg dose) and continue to be silent. We are a minority of one and have been told to stay away upon severe penalties. We may face some tough personal decisions as this progresses."
June 27, 2000: An email (Exhibit 528) summarizes a teleconference among Bayer executives to discuss Baycol problems with rhabdo. The email states: "Patient information leaflet should be prepared before 12 July 2000 when a meeting is scheduled with the FDA to discuss labeling for 0.8 mg tablet. Paul mentioned that this leaflet should not be distributed prior to 0.8 mg Baycol approval, otherwise it will most likely delay the approval."
June 30, 2000: A Bayer Corp. document from Roger Celesk from a Bayer Corp. executive states that there have been 53 rhabdo deaths worldwide associated with the Baycol 0.8 mg dose.
July 7, 2000: An email to Ernst Weidman states: "Overall, it looks like there is a continuing problem which is dose related. If FDA is already tuned in to this, you may have some resistance about the higher dose. Also, what further efforts are you prepared to take to inform providers and patients?"
July 10, 2000: A hand-written note at the bottom of a memo outlining a telephone discussion involving several Bayer executives (Exhibit 99) indicates a "very strong signal" involving Baycol. A signal is a term used to denote the fact that negative information has been received about a drug.
Aug. 1, 2000: In a letter to doctors announcing a new Baycol 0.8 mg dose (Exhibit 528), Dr. Richard Goodstein and Dr. Neil Shusterman state: "A proven safety profile? Recommended starting dose is Baycol 0.4 mg once daily in the evening, but when you need even more power, reach for Baycol 0.8 mg -- premium cholesterol reduction power, at a price your patients can appreciate."
Aug. 11, 2000: In an urgent email from a Japanese doctor involved in Baycol tests (Exhibit 1656), Dr. Sasaki strongly recommends that Bayer "stop the drug administration in all treated patients due to high frequency of CPK increase and the occurrence of rhabdomyolysis during the clinical trial." The email also states: "Dr. Yamamoto recommended that Bayer immediately discontinue the development of cerivastatin (Baycol) at higher doses." (Emphasis in the original)
Dec. 20, 2000: A company email discussing Japanese concerns about rhabdo (Exhibit 1666) states: "Our colleagues were very upset at Bayer's lack of response to Takeda in this matter." World Health Organization data shows the frequency of rhabdo in Baycol patients was 2.1 percent compared with 0.2 percent to 0.5 percent in other statins.
March 26, 2001: A Bayer memo (Deposition Exhibit 43) outlining recent telephone discussions among Bayer drug safety officials says the Baycol label is not good enough to discourage people from starting on the 0.8 mg dose. The memo states: "It was agreed that current dosage labeling was inadequate to discourage a starting dosage of 0.8 mg. Spontaneous reports of death in the U.S. (12 since the beginning of the year) were overwhelmingly associated with use of the 0.8 mg dose. Only one of these cases noted concomitant use of gemfibrozil."
Jan. 25, 2001: A Bayer email (Exhibit 1706) states: "Ralph, this does not reflect well on Bayer. ? The issue of Medical ethics and integrity (or lack thereof) is disturbing." Another email states: "Ed, Bayer has been a real pain on the study we are doing with respect to rhabdomyolysis, and their product. They are insisting on intellectual property rights which we have never relinquished in other contracts. To relinquish or compromise our ability to publicly communicate this type of problem could potentially open us up to medical-legal liability issues."
Feb. 26, 2001: Bayer projects Baycol sales in excess of $1 billion in 2003. (Exhibit 351)
Aug. 8, 2001: Baycol is recalled in the United States.
Scott Williams is a freelance journalist based in Corpus
Christi, Texas. He wrote this article for the Baycol
Legal Alliance. www.baycol-lawsuit-news.com/timeline.htm.
Copyright Calliope Media, Inc. © 2011 --- All Rights Reserved.