Did Chelsea Laboratories Steal Glaxo Secrets?

Glaxo Wellcome (Research Triangle Park, NC) claims in a lawsuit that former Burroughs Wellcome employees passed along the secret recipe for Glaxo's antidepressant drug, Wellbutrin (bupropion), to generic drug maker Chelsea Laboratories (Monroe, NC). Glaxo is asking a North Carolina U.S. District Court for an injunction preventing Chelsea from using any of allegedly stolen information to make a competing generic drug. In its lawsuit filed March 30, Glaxo claims former Burroughs Wellcome employees gave Chelsea the recipe, a trade secret belonging to Burroughs Wellcome before it was taken over by Glaxo Inc. in 1995.

"The information was not generally known, nor is it readily ascertainable through independent development or reverse engineering," the lawsuit charged. Ramona Jones, a Glaxo spokeswoman, said on April 21 that Glaxo hopes to resolve the dispute out of court.

Chelsea Denies Wrongdoing
Chelsea Laboratories recently was sold by Hoechst Marion Roussel USA to Watson Pharmaceuticals Inc., a generic drug maker in Corona, CA. Allen Chao, chief executive officer of Watson Pharmaceuticals, said, "We cannot really comment, but I can tell you categorically that Chelsea did not do anything wrong."

Burroughs Wellcome first marketed Wellbutrin as an immediate-release "atypical" antidepressant 1989, to compete against selective serotonin release inhibitors (SSRIs), a new class of antidepressant to which Prozac (Eli Lilly and Co.), Paxil (SmithKline Beecham), and Zoloft (Pfizer, Inc.) belong. The patent on bupropion expired in 1994 but thus far no generic versions of the drug have appeared. Since patent expiration Wellbutrin has been introduced as a sustained release formulation (Wellbutrin SR). It was then repackaged, at a smaller dosage, as Zyban, for smoking cessation therapy.

Sales of Wellbutrin IR and SR totaled $240 million in 1997, up from $120 million in 1996. Sales have been bolstered by introduction of the SR version and through a marketing campaign touting the drug's lower incidence of adverse sexual side effects (mostly impotence in men). Zyban sales in the U.S. were $52 million in 1997, representing 85% of new prescriptions in the smoking-cessation market. Taken together, the SR and IR formulations of Wellbutrin represent Glaxo Wellcome's fourth largest-selling drug, but only amount to about 4% of the antidepressant market and just about 10% of the sales of Prozac, the antidepressant market leader.

Reverse Engineering, or Corporate Espionage?
One would think that, armed with the active's chemical structure, a list of tablet ingredients, and a sample of the drug in question, an experienced pharmaceutical scientist could reverse engineer almost any drug in any formulation. Not so, says Ramona Jones of Glaxo Wellcome. "Wellbutrin tablets are not easy to reverse engineer," Jones told Pharmaceutical Online. The process for producing the tablets is not easily deduced without information that we consider to be trade secrets. It took Burroughs Wellcome years to perfect this process. After examining Chelsea's manufacturing technique we doubt they could have arrived at a process so similar to ours without having inappropriate knowledge. Our complaint is simply aimed at preventing them from using this knowledge, not at preventing them from formulating a generic bupropion."

So what, specifically, is so special about Wellbutrin, that it took "years" to formulate the drug in the first place, and that - given the full disclosure regarding its ingredients - prevents its recipe from being reproduced in a matter of days or weeks? Jones would not or could not divulge "technically what is complicated about this process [the formulation] or its similarity to our process which has aroused suspicion in our technical people."

Tabletting and formulation are by no means trivial activities, but traditionally they do not carry the same uncertainty as drug discovery or clinical testing. So it is difficult to fathom how it could have taken "years" for Burroughs Wellcome to create Wellbutrin tablets or why, under the circumstances, it should take very long to duplicate the feat. Glaxo's Jones could not answer this question adequately, and Chelsea Laboratories' telephone went unanswered on Thursday, April 23. Given the legal climate and the stakes for Chelsea, this is not necessarily an indictment of the company.

The answer may soon become available. In their suit, Glaxo Wellcome has asked for "accelerated discovery," which would provide Glaxo with Chelsea's notes and other documents almost immediately, to determine if Chelsea circumvented normal reverse engineering protocols. If granted, accelerated discovery could resolve this dispute on the spot. More likely, it will raise more questions than it answers.

By Angelo DePalma

For more information: Ramona Jones, Public Affairs, Glaxo Wellcome, 5 Moore Dr., Research Triangle Park, NC 27709. Tel: 919-483-2839. Fax: 919-549-7459.