‘Mr. Botox’ Case Raises Some Brows

They call him “Mr. Botox” for good reason.

Arnold W. Klein, dermatologist to the stars, claims to have pumped the anti-wrinkle drug into more faces than inhabit the entire city of Newport Beach. He has talked up the purified toxin at small charity events in expensive restaurants and at international conferences in glittering halls.

Along the way, he has received hundreds of thousands of dollars in fees from Botox manufacturer Allergan Inc., which pays him for acting as a “media spokesman” for the drug and lending a hand with other consulting chores.

Such arrangements typically are secret, but Klein’s contract surfaced in a medical malpractice case filed by Hollywood wife Irena Medavoy against the Irvine-based drug company and the Beverly Hills doctor.

The injury-by-Botox lawsuit, set for trial this month in Los Angeles Superior Court, provides a rare look at the relationships between drug companies and the physicians who consult for them. Klein, along with dozens of others, has lined up behind Allergan’s biggest drug to serve as both advisor and cheerleader.

Klein not only served as a mouthpiece, but he also agreed to review advertising plans and offer advice on clinical trials, according to a copy of his contract in the court record. His duties included teaching other doctors to inject the anti-wrinkle drug.

And he wasn’t alone. Forty doctors were groomed by Allergan’s public relations experts to act as media spokesmen for Botox, and the company had 300 doctor’s offices and medical clinics in its official network of Botox training centers, court documents show.

Jerome Kassirer, a former editor of the New England Journal of Medicine, said Allergan, in asking more from some physicians than medical advice, was “turning doctors into sales reps.”

As for Klein, Kassirer said: “It is clear he is being paid to promote the drug.”

Medavoy’s suit against Klein and Allergan made headlines when it was filed last year, and not only because she was the wife of movie producer Mike Medavoy, the studio chief behind “Rocky” and “Annie Hall.” Klein, 59, was a clinical professor at UCLA’s David Geffen School of Medicine, an unpaid position, and well known in Hollywood, where his celebrity patients included Elizabeth Taylor and Michael Jackson. Last month, UCLA announced that some of Klein’s friends had anonymously pledged at least $1 million to endow a dermatology chair in his name.

Medavoy, 45, claims in her suit that Botox shots administered by Klein made her ill and that Klein and Allergan misled her about the drug’s safety. He and the company have denied the allegations.

Klein’s contract with Allergan, as outlined by Allergan’s director of aesthetic marketing in court documents, provided Klein with quarterly payments of $25,000 for all his consulting duties. If Klein attended meetings at the request of Allergan, he received an additional $10,000 a day, plus travel expenses. When local sales reps scheduled an appearance for him, Klein collected $2,000 to $4,000.

He or his company, Minimally Invasive Aesthetics, received a total of $499,000 from Allergan between September 2000 and December 2003, court records show. Kassirer, the former medical journal editor, now a professor at Tufts University School of Medicine, called the amount “huge -- far in excess of anything I have heard anywhere.”

Allergan general counsel Douglas S. Ingram would not discuss Klein’s contract. However, Ingram said that consulting deals were common in the drug business and that none of the company’s contracts was unusual. He said consultants provided the company with medical insights and advice and were not recruited to promote drugs.

Providing Guidance

The industry relies on guidance from consultants “to develop and make available better products to the medical community and patients,” Ingram said, adding: “Dr. Klein is an expert in the use of Botox and has been benefiting patients with Botox for many years.”

Neither Medavoy nor Klein would comment for this story. Medavoy’s lawyer, Arthur Leeds, didn’t return calls. Klein’s lawyer, Howard Weitzman, said he didn’t want to discuss the case before its Aug. 31 trial date.

Although consulting contracts between academics and drug companies are widespread, some high-profile deals recently have come under scrutiny. The National Institutes of Health, the nation’s premier medical research organization, was criticized last year for allowing its top scientists to advise drug companies. The NIH is revising its ethics policy to prevent conflicts of interest.

Ingram said Klein wasn’t acting on behalf of Allergan in his medical practice. “Nothing could be further from the truth,” he said.

There’s no question that Klein has been an enthusiastic booster of Botox. Klein lectures extensively on Botox in the United States and around the world, according to his own website. South Koreans call him “Mr. Botox,” Klein once said. Last year, the British style magazine Harpers & Queen named him Hollywood’s top Botox doctor.

Klein “likes to get out and speak and help train other people,” Tom Albright, vice president of Botox global marketing, said in a deposition. “He will actually go out to a dinner meeting, if it doesn’t interfere with patient practice, and lecture a group of doctors” about Botox.

In an interview with Los Angeles magazine two years ago, Klein said he had injected 90,000 patients. “Collagen solved the biggest problem of a woman’s face, the lower third, and Botox was a home run to the forehead,” he told the magazine.

Botox is a purified form of a deadly poison called botulinum toxin, which blocks nerve impulses to muscles. When tiny amounts of Botox are injected into muscles, they relax. The effect lasts three to four months.

Until 2002, Botox was an approved treatment for only a handful of medical conditions -- crossed eyes and muscle spasms affecting either the neck or eyelids. In the mid-1990s, Klein and other dermatologists began experimenting with it as an anti-wrinkle treatment. Two years ago, the Food and Drug Administration approved Botox as a cosmetic treatment but only for glabellar lines -- wrinkles between the eyebrows.

Allergan’s successful promotion of Botox drove sales of the drug to $564 million in 2003, 32% of the company’s total revenue of $1.75 billion. Last year, the Society for Aesthetic Plastic Surgery said Botox injection had become America’s fastest-growing cosmetic procedure.

Twice in the last two years, the FDA has warned Allergan about ads that, in the agency’s view, minimized side effects and implied Botox was approved “for use in all tough wrinkles.” The agency required Allergan to change the ads. The FDA doesn’t regulate doctors.

Off-Label Uses

Since 1999, Klein has written more than two dozen articles about Botox, many of them in publications aimed at dermatologists. Klein coauthored a 2002 article in the Archives of Dermatology that provided how-to advice; it was accompanied by diagrams that showed where Botox should -- and shouldn’t -- be injected for wrinkles around the eyes, chin and lips and on the forehead. Klein also has written about unapproved uses outside the field of dermatology, such as injecting Botox to prevent migraine headaches.

Allergan doesn’t use its consultants to promote so-called off-label treatments on its behalf, Ingram said. “We don’t promote off-label uses, and consultants do not have [that] marketing function,” he said.

Klein’s writings about unapproved treatments nonetheless are beneficial to Allergan, said Kassirer, who has written a book on the relationships between doctors and drug companies.

“Doctors will listen to him because he is an avowed Hollywood expert,” Kassirer said. “That’s what makes him so valuable” to Allergan.

The contract between Klein and Allergan figures into Medavoy’s lawsuit. She said that Klein should have told her about his financial arrangement with Allergan and that she would not have consented to treatment had she known about it. She claims that keeping the contract secret was an unfair business practice.

One legal expert said that aspect of Medavoy’s suit might resonate with a jury.

“She may not be using these exact words, but what she is saying is that there was a conflict of interest,” said Marjorie Shultz, a professor at UC Berkeley’s Boalt Hall School of Law.

Eric Rakowski, also a Boalt Hall professor, said the consulting contract was irrelevant.

“If doctors had to disclose any time they got money from a drug company, then a large number of academic physicians would be guilty of malpractice,” he said. “It is not typical to disclose such relationships.”

The plotline of Medavoy’s suit is widely known. Seven days after she received Botox injections in March 2002, Medavoy said, she became ill. Klein had given her shots to smooth creases in her forehead and near her eyes. Klein also had injected Botox into each side of her head and her neck to treat her migraine headaches.

Medavoy blamed Botox for her symptoms, including an unrelenting headache that kept her sidelined for months.

“I missed the Vanity Fair Oscar party, missed going to the Oscars,” she told Vanity Fair magazine last year. “We were going to spend the month of June in Europe, going to Paris and then on a boat in the South of France. I missed that. People had invited me to Aspen for August. I missed that.”

Medavoy said that neither Klein nor Allergan fully warned her about Botox’s side effects and that Klein never told her that Botox was not an approved headache remedy. The company and the doctor used her as a “guinea pig,” she claimed.

Her suit seeks unspecified damages and an order that Botox doctors tell their migraine patients whether they have received money from Allergan.

Klein and Allergan said in court documents that Botox didn’t make Medavoy ill and that they did nothing wrong. Allergan said it listed the side effects associated with Botox, including headache, on the product’s package insert, as required by the FDA. The company said it had no control over what doctors tell their patients or how doctors use the drug.

Allergan lawyer Ingram said the company was looking forward to the trial so it could address any doubts about the safety of Botox.

“We are confident in our belief that her complaints are not related to Botox,” he said.