With Pfizer's first-in-class HIV drug set to launch next month, the company looks to be sitting pretty in the novel entry-inhibitor niche. Maraviroc, which blocks the most common pathway HIV uses to infect cells, will offer patients with resistant virus a potent treatment option. And forecasters predict that the drug, which will be branded Celsentri, will put a cool $500 million in Pfizer's pocket come 2011--not bad, since the HIV market is valued at about $8 billion.

And thanks to Pfizer's worldwide expanded-access program (EAP), people with HIV are already clamoring for the drug. EAPs, which offer free drugs in exchange for patient data, are fast becoming necessary marketing tools, especially in patient groups with life-threatening diseases and limited healthcare resources. Merck recently set up an EAP for its integrase inhibitor Isentress (raltegravir), and Tibotec launched an EAP prior to the 2006 approval of Prezista (darunavir). "EAPs are quite important in getting the word out about these new drugs," said Datamonitor infectious-disease analyst Mansi Shah.

That's especially true in Pfizer's case. Both GlaxoSmithKline and Schering-Plough had CCR5 inhibitors in their pipelines, which may have sent the juggernaut into a panic. Pfizer ex-VP-turned-whistleblower-blogger Peter Rost claims that  the company slipped to the illegal side by using its sales force to recruit new subjects and access sites. But neither FDA nor the mainstream media has shown any interest in the charge from the oft-charging Rost. Meanwhile, Schering-Plough's entry inhibitor vicriviroc has not yet entered Phase III testing--though it'll do so shortly--and no one's seen hide nor hair of Glaxo's CCR5 inhibitor since the company halted its Phase III trial of aplaviroc in late 2005. This currently leaves maraviroc the sole hope for some HIV patients--and the sole beneficiary of the CCR5-antagonist market.

A notoriously mutable virus, HIV sooner or later renders virtually all 27 HIV available drugs powerless. "There will always be a need for new HIV drugs," Shah said. "So many patients now are resistant to all the other drugs out there, there's a constant need that has to be met." These experimental drugs might take several years to complete Phase III trials, but with EAPs, she added, more patients can receive drugs that might work.

In addition, the conventional consumer-push strategy falls short for serious diseases requiring complex--often combination--treatment. "With oncology drugs and HIV drugs, you get a lot less direct-to-consumer advertising," said Elgar Peerschke, global healthcare head  of Bain & Co. "You don't want to put false hopes out there for everyone." He added that HIV has strong patient advocacy groups, and that companies are often better served by reaching out to these groups and educating them--though with five classes of competing drugs, just stating the facts isn't enough. "Now, you need to have a posture, a message," Peerschke said.

But while EAPs can be a godsend to patients, they can pose a significant risk to companies. While AIDS advocates argue that the strict medical criteria of EAPs unfairly exclude patients who need the drug, Peerschke noted that too many subjects can make the study go bust.

"You need to have control of the study," Peerschke said.  "The more people you take in, the more diverse the conditions, the harder it is to interpret the results."

Balance, then, is the key. But besides stabilizing the subject pool while being sensitive to patients' needs, companies also have to keep their sales reps cutting-edge smart, and with HIV research and drug development evolving almost as quickly as the virus, that can be tough.

"Companies are finding it increasingly difficult to keep their sales force up-to-date," Peerschke said. "But with most physicians in the field being investigators, that's something they have to do."

This story has been corrected to remove an error.

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Maraviroc's promise shows the value of expanded-access programs

Global Access for Pfizer's New HIV Drug

Last week brought bad news for Sanofi-Aventis's weight-loss drug Acomplia, which, in turn, was good news for the launch of GlaxoSmithKline's over-the-counter competitor, Alli. FDA's advisory committee unanimously voted against approval for Zimulti last Wednesday, but GSK's celebration may be cut short if the same curse that hangs over Acomplia--hard-to-market side effects--turns around and bites Alli in the butt.

The two drugs couldn't be more different. GSK's Alli (orlistat) inhibits the body's ability to absorb fat, while Sanofi-Aventis' Acomplia (rimonabant) checks the mind's urges toward excess eating. Both are vying for a big, fat piece of the $46 billion diet pie.

Approved for OTC use earlier this year, GSK's new golden child is really just a half-dose of Roche's Xenical, which showed only modest weight-loss benefits to begin with. Not that customers were unduly worried: On Thursday, its first day of national sales, shoppers were snatching up the $60 packs of Alli as fast as they could. Most buyers of the antiobesity pill were women--"and they're not fat," one pharmacist told the 

The Sanofi diet drug--renamed Zimulti after FDA nixed Acomplia as too close to accomplish--was the first in its class, though, blocking the same brain receptors marijuana chemical THC acts on. With its novel mechanism of action and solid efficacy data, this anti-munchies med was the talk of the industry, generating enormous media and consumer interest. 

And that was music to the struggling French drug maker's ears. "Sanofi needs a new blockbuster to boost its future, and Zimulti was going to be it," said Hoover's Finance and Health Care Editor Nell Newton. In Europe, Acomplia sales topped $41 million last year, but the US market, with its high rate of obesity, promised to deliver that and more.

"The buzz was so positive that it was hard to believe," said University of the Sciences in Philadelphia professor Dr. Daniel Hussar. "This was going to be a miracle--it had to be too good to be true."

Meanwhile, Sanofi's supposed savior has been sitting on FDA's to-do list for a year and a half now--the agency must make a decision by July 26--and the future looks grim. Some panelists are even calling for a deadline extension until 2010. Sanofi shares plunged following the FDA committee's announcement.

All the hullabaloo stems from data that indicate suicidal thoughts, depression, and other mental problems were twice as prevalent in subjects on Zimulti. The FDA report also notes a risk of adverse neurological events like seizures, which is triggering a second look at the drug by the European Medicines Agency. Sanofi officials, not surprisingly, are offering a more positive take on the results, pointing out that there's no proof of a causal relationship between Zimulti and psychological malfunction. Still, they say they'll now give each subject in current studies a suicidality questionnaire at every checkup.

Newton isn't surprised by Zimulti's failure. "But I am still rather appalled by the stubbornness with which Sanofi is defending its product," she said, though she does understand the company's need for a cash cow to replace its blockbuster Plavix, which faces generics threats.

Even if Zimulti is eventually approved, a host of marketing issues lie in wait. There are already jokes about the difficulty of advertising a drug that makes you lose weight--and your mind.

While less serious, Alli's side effect is so unpleasant that Sanofi may be set to enjoy a tasty dish of schadenfreude. Because Alli prevents fat absorption, undigested fat passes through the body in some unappetizing ways. Glaxo has put $150 million toward marketing Alli, giving customers a flurry of recipes, online tools to record eating and lifestyle habits, and a blog (www.alliconnect.com)--not to mention some creative ways to soften the blow of the product's downside. The "bowel movement changes" that can result from eating too many French fries are not side effects, says the company; they're "treatment effects." GSK marketers, ever optimistic, are informing consumers that this is a sign they should be cutting back on the amount of fat in their diets.

Though the product is flying off shelves right now, Glaxo might need another $150 million round of advertising to coax dieters back. Even now, they're advising Alli takers to wear dark clothing and carry a spare pair of underwear--not necessarily a lifestyle change that dieters may want to make.

"Face it," Newton said, "anything that causes folks to have greasy skidmarks in their underpants is likely to bring with it some marketing headaches."

FDA fears may prevent a showdown between two weight-loss heavyweights.

Pharmaceutical Executive-06-20-2007

Global Access for Pfizer's New HIV Drug

Allez, Alli, But Acomplia, We Hardly Knew Ye