Off-label marketing: How testosterone replacement got big

McClatchy NewspapersJune 13, 2011 

20110613 TESTOSTERONE

Dreams of what might be

LEE HULTENG / MCT

WASHINGTON — The question for doctors was simple: "When a patient comes in and asks for Viagra, will you first screen for low T?" meaning testosterone.

The pitch by Solvay Pharmaceuticals Inc. was part of its effort to make its testosterone replacement drug AndroGel "ride (the) coat tails of Viagra."

But unlike Viagra, AndroGel wasn't approved by the Food and Drug Administration to treat erectile dysfunction.

Instead, it was approved to treat a relatively specific condition of the sex glands called hypogonadism. According to a significant whistleblower lawsuit, Solvay wanted to boost AndroGel's sales with an aggressive strategy to push "off-label" — or unapproved — uses of the drug.

"I can't underscore enough how important off-label sales were," said John King, a former sales manager for Solvay who's involved in the suit. "You can do the math: If we had truly stuck to the FDA approved indication, AndroGel would never have had anywhere the sales it had."

While they're a big part of any drug makers' bottom line, such off-label uses also can run afoul of federal drug-marketing laws. It's legal for physicians to prescribe drugs off-label, often based on their assessment of the latest medical research, but it's illegal for drug makers to promote such uses.

The FDA's regulations on prescription medicine are based on researchers proving the safety and effectiveness of individual drugs for treating specific illnesses. Prescribing drugs to combat illnesses they were never approved to treat can be ineffective and risky to patients.

While off-label marketing long has been commonplace, federal prosecutors in recent years have cracked down on the practice, bringing more than a dozen cases against drug makers for off-label marketing, and winning billions of dollars in criminal and civil settlements. The cases have revealed how companies and their on-the-ground sales reps ignored drug-marketing laws to convince doctors to prescribe drugs for unapproved conditions. Private whistleblower suits have been a part of that crackdown.

The current whistleblower lawsuit actually involves three of Solvay's drugs — AndroGel, a blood pressure drug, and a mental health drug — and provides an inside look at the world of corporate drug marketing. Although filed several years ago, details in the lawsuits were only recently unsealed at the U.S. federal courthouse in Houston. Dozens of internal company memos, emails and sales presentations were filed in the case, documenting how the company and its sales representatives sweet-talked, cajoled and even paid fees to the doctors in their territories.

AndroGel, a clear gel that men rub on their shoulders, upper arms and abdomen, has been through three corporate owners in the past dozen years: Unimed Pharmaceuticals Inc., which was bought by Solvay Pharmaceuticals Inc., which was in turn bought by Abbott Laboratories. According to Abbott, it has annual U.S. sales of more than $600 million.

The attorneys handling the case said that neither they nor Solvay would respond to McClatchy's questions, other than to note that federal and state governments, which sometimes join similar cases, have declined to do so in this case.

The drug's current owner, Abbott, said through a spokesman that the case was filed in 2003, nearly seven years before Abbott's acquisition of Solvay and that, "No specific concerns have been raised in this case about Abbott's sales and marketing of these products." Spokesman Scott Stoffel added that AndroGel is approved for the treatment of men with no or low testosterone and Abbott markets AndroGel according to the medication's label.

Hypogonadism, the condition that AndroGel got the FDA okay to treat, is defined by low levels of the male hormone testosterone, often because of damage — from injury, chemotherapy, or other trauma — to the testes. It can result in low sex drive, low energy levels, muscle loss and depression.

How many men suffer from this condition? Those numbers are all over the map.

In 1999, when Unimed asked the government to approve the drug, it announced that hypogonadism was estimated to affect more than "one million American men."

In 2000, when the FDA approved the drug, the company announced that the market was "four to five million American men."

But by 2003, when drug was being pushed by its corporate managers, the number drifted to "up to 20 million men," according to information in the lawsuit.

From the start, Solvay — which then owned the drug — wanted to expand the market. In one document, the company noted it needed to expand the testosterone market by 36.5 percent, particularly by pushing the drug to primary care physicians. It sought to convince doctors that low levels of testosterone were widely under-diagnosed, and that conditions associated with normal aging could be because of those low testosterone levels.

It's clear from internal memos that Solvay considered some doctors — including those in primary care — to be relatively easy marks.

A New Orleans district sales memo described primary care doctors as "easily influenced."

A 2004 memo on AndroGel sales strategies said the sales force was putting extra emphasis on rural areas, since "rural doctors are typically very accessible, give us plenty of time to teach them the right way to diagnose and treat, and they have the patients."

Treating low testosterone is tricky, in part because experts still struggle to determine what a normal testosterone value should be. A blood testosterone value of more than 300 is considered normal, said Neil Goodman, a Miami endocrinologist and chairman of the reproductive medicine committee of the American Association of Clinical Endocrinologists. A value below 150 or 200 is low. But the meaning of levels between 200 and 300 can be ambiguous, and dependent on a man's age as well as any other underlying medical conditions.

Beyond that, there are problems with the testosterone test itself. "If you sent the same sample to three different labs, you might get three different results," Goodman said; federal officials and medical experts are working to standardize testing.

One of Solvay's strategies was to get doctors to rethink the idea that the cutoff between normal and low was 300. Instead, company sales documents discussed what was called "andropause," a condition akin to menopause.

The FDA had addressed the andropause issue before. In 2000, when reviewing the drug's advertisements, the FDA told the AndroGel's maker that "claims and representation that suggest that AndroGel is indicated for men with 'age-associated' hypogonadism or 'andropause' are misleading." The drug, the FDA said, was only approved for men with hypogonadism.

In a 2001 sales memo from the company's Mid-Atlantic region, however, a company official suggested that might be too restrictive, the lawsuit says. If a patient's testosterone had dropped over time — even if it still was in the normal range — then he might need AndroGel, documents show.

"We can help write a new paradigm. One that captures both the andropausal male, as well as the hypogonadal male," a sales document said, according to the lawsuit. Sales reps were told to ask doctors to examine how far a man was "from the top of the normal range, rather than how close he is to the bottom of it."

Beyond the message itself, Solvay used a range of tactics to connect with and convince doctors to prescribe the three drugs in the lawsuit.

According to court records, Solvay paid doctors between $150 and $1,000 for "preceptorships," which allowed drug sales representatives to shadow them for a day; held "Lunch-N-Learn" programs, where sales representatives brought food into physicians' offices and would proceed to give them pitches for their drugs; and held "Dine-N-Dash" programs that allowed doctors to pick up a fancy dinner as long as they listened to a short pitch.

In a memo to people on his sales team, King — the former sales rep involved in the lawsuit — laid out the rationale for such "peer influence programs."

"Here is the bottom line with these programs: THEY WORK. They have worked in a big way in the Houston district and the recent feedback from Raleigh is extremely positive. Think about it.....the doctor is away from the office, not stressed, and he is getting to do something nice for himself and his family."

If successful, King and another plaintiff could get a cut of any drug-company payout.

In a recent court reply, attorneys representing the drug maker scoffed at the allegations of a "decade-plus, multi-drug, nationwide scheme of False Claims Act violations... Despite page after page of narrative about these purported 'schemes,' (the lawsuit) offers no particularized allegation of false claims that (Solvay) 'caused' anyone to submit by improperly promoting a drug off-label, paying a kickback, or 'manipulating' a diagnosis code."

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