Molecules and Marketing

Yet as a relative latecomer to the HIV field—albeit armed with "one great molecule and one brilliant insight," in Sanford C. Bernstein biotech analyst Geoffrey Porges's words—Gilead has always depended on the power of marketing. Its one great molecule, Viread (tenofovir), was a 2001 entry into the crowded class of nukes (nucleoside/nucleotide reverse transcriptase inhibitors) that added value because it was the first once-daily HIV pill. For patients who were used to gulping down a handful of pills, Viread helped meet the critical goal of improving adherence—and, therefore, averting viral resistance and treatment failure.

After swiftly buying a second nuke, Emtriva (emtricitabine), Gilead set into motion its make-or-break plan to wrest the market from GSK's grasp. The biotech bundled Viread and Emtriva into a single pill and in 2004 launched it as Truvada—against the reigning double-nuke fixed-dose, GSK's Combivir, which had become the go-to base for building HIV cocktails. Once-daily Truvada was not only a simpler regimen than twice-daily Combivir—it also proved to be a little more potent and a lot more tolerable.

This may all be par for the course in pharma marketing, except that in HIV treatment, switching patients from one combination to another is a very risky business. Still, as Jim Edwards wrote in reporting the story on his BNet pharma blog in 2009, after the plaintiffs dropped the lawsuit following the Department of Justice refusal to intervene, "One must also assume that the case was not that strong or was otherwise flawed—in other words, it's wise to give Gilead all the benefits of the doubt."

When asked about the suit, Gregg Alton, Gilead's head of corporate and medical affairs, says, "I was involved in that launch and we did everything in the most ethical way possible. No one is more honest than Kevin Young. But when money exchanges hands between doctors and pharmaceutical companies, the lines can get fuzzy."

A doctor who was witness to the Truvada marketing campaign and who asked not to be named says, "The suit should have gone forward."

HIV Profits, Patents, and Products

In the last quarter of 2009, Atripla (up an annual 51 percent to $2.4 billion) outpaced Truvada (up an annual 18 percent to $2.5 billion) as the best-selling product. Even Viread, one of many single compounds long surpassed by the fixed-dose standard, eked out a growth spurt (up 7 percent to an annual $667.5 million)—only slightly below the market average of 10 percent. But between patent expirations (Viread's ends in 2017) and pricing pressures, the HIV market is expected to begin to decline between 2015 and 2019, according to Datamonitor.

Early ripples are already issuing. Gilead recently had to lower its 2010 total-sales projections by 10 percent to $7 billion, a result of federal cost containment. To the generous price concessions of 15 percent that Gilead already offers ADAP patients, including discounts and freezes through 2013, the government will tag on another 8 percent. As for patent erosion, with BMS's Sustiva losing exclusivity in 2013, Atripla faces a stormy future from generics. This prospect sparked Gilead to license Tibotec's experimental non-nuke rilpivirine for a new fixed-dose formulation with Truvada. A marketing effort to switch Atripla patients to the new combo could limit the damage to Gilead's bottom line.

But the Quad is Gilead's extravaganza—a once-daily pill containing Truvada plus two in-house experimental compounds, the integrase inhibitor elvitegravir and the PK booster Cobicistat. "We're likely to see the Quad take away from some sales of Atripla," says Kevin Young. "Atripla was a fundamental step change in HIV, and over half of all people with HIV are taking it. Now the Quad will offer a fundamental step change over Atripla." So eager is Gilead to do so that it has even bankrolled a head-to-head trial showing that the Quad and Atripla have comparable efficacy. But the Quad will also vie with combinations containing Merck's first-in-class integrase inhibitor, Isentress. "It's too early to tell how elvitegravir compares with Isentress," says Datamonitor healthcare analyst Nele Jensen. "Gilead may have decided to coformulate it with Truvada because it's not as effective. We don't expect elvitegravir to do well as a standalone because a third integrase from Glaxo showing impressive data is expected in 2016."

Gilead has won the praise of activists for developing Cobicistat, a welcome alternative to Norvir, whose side effects are legion. Says ATAC's Jeff Taylor: "Gilead should be congratulated not only for taking on this niche but for committing to marketing it as a single agent. They refuse to play the Abbott game of bundling it with only its own drug so as not to make it available for use with other combinations." If Cobicistat lives up to its expectations, HIV doctors can be expected to dump the Abbott booster with a vengeance.

Gilead also gets high marks for its pricing and access practices in the developing world. In 2006, it started offering licenses to 13 generic drugmakers in India to produce copycat Viread and Truvada for sale in the developing world (excluding key emerging nations). "The bigger pharmas may not have liked what we did—giving away patents—but that's Gilead's way of doing things differently," says Young. By the end of 2009, only three of the Indian knockoff firms had received approval for Gilead drugs, although the number of people in the developing world on Viread-based drugs had risen to 700,000, split about equally between brands and generics. Eager for more progress, Gilead began talking up UNITAID's proposal of a patent pool among other HIV drugmakers, and at July's International AIDS conference in Vienna it was reported that Gilead, Tibotec, and BMS were warming to the once-radical notion of giving their patents away for free to help stop the still-exploding global epidemic.

Yet the great unmet medical need in HIV is among people who have burned through all their options. With viral suppression a lifelong necessity, drug failure is almost inevitable—and a growing number of patients are at the end of their treatment hope. "What Gilead is coming out with is great, but it would be greater if they had produced a drug with a unique resistance profile," says Taylor. "That's why the GSK integrase inhibitor is so important to the HIV community."

The GSK integrase inhibitor that has tongues wagging is the centerpiece of the pipeline at ViiV Healthcare, a joint venture between Pfizer and GSK, which has 85 percent control. With $2.4 billion sales expected in 2010, ViiV isn't an immediate threat to Gilead, but it has five compounds in Phase II, including the anti-integrase agent promising high potency, low toxicity—and a unique resistance profile. With sufficient backing, ViiV could enable GSK to win back some of the turf it ceded to Gilead.