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Gilead's Much-Awaited Quad Gets Timely FDA Nod in HIV

By Jennifer Boggs
Managing Editor

Gilead Sciences Inc.'s four-drug, single-tablet HIV drug Quad got its much-anticipated approval Monday, and the drug is expected to shore up the firm's top-selling HIV franchise, which brought in $7.05 billion in revenue in 2011 but faces patent expiries starting in 2018.

The FDA nod for Quad, branded Stribild, which combines the ingredients of Truvada (emtricitabine/tenofovir disoproxil fumarate) plus elvitegravir and boosting agent cobicistat, came after market close but was largely expected. The drug got a 13-1 vote in its favor during a May Antiviral Drugs Advisory Committee meeting and, in an unusual move by the International AIDS Society-USA, was included, ahead of its approval, in the IAS-USA guidelines released during the AIDS 2012 meeting in Washington last month. (See BioWorld Today, May 14, 2012.)

While consensus estimates are projecting a modest launch for Quad, which Gilead has said it is ready to roll out for treatment-naïve HIV-1-infected patients as soon as approved, the Foster City, Calif.-based firm's track record for strong HIV launches means the drug could hit blockbuster status in just a few years. After all, Gilead's Atripla, which combines Truvada plus Bristol-Myers Squibb Co.'s Sustiva (efavirenz) topped $1 billion its second year on the market, and Quad is expected to be priced at a premium to Atripla's $21,000-per-year cost.

The company could not be reached as of press time, but pricing has proved the most contentious issue for Quad. Even before Gilead had disclosed the drug's cost, objections were being raised. In a letter to the company's chairman and CEO, John Martin, 13 House members last week claimed that an anticipated price tag in the range of $26,000 to $34,000 per patient per year could cause a funding crisis for state-run AIDS Drug Assistance Programs. (See BioWorld Today, Aug. 16, 2012.)

Deutsche Bank analyst Robyn Karnauskas, who last week predicted a price range of $26,000 to $29,000 based on comments from Gilead management, has modeled Quad sales of $85 million in 2012 and $746 million in 2013, well above consensus projections of $45 million and $400 million, respectively.

All told, analysts have predicted that Quad could end up generating as much as $4 billion per year, though more conservative estimates have pegged the drug's potential to be limited by the fact that it showed only noninferiority to Atripla – rather than superiority – which could put it at a disadvantage when generic Atripla hits the market in 2018.

Quad follows on the heels of Gilead's other single-tablet regimens – Atripla and Complera, which combines Truvada plus Johnson & Johnson's Edurant (rilpivirine) – but is the first single-tablet drug co-formulated with an integrase inhibitor.

The Magic of Integrase Inhibitors

Designed to block the action of viral enzyme integrase, which inserts the viral genome into the DNA of a host cell, integrase inhibitors work by stopping that integration in the retroviral replication process, thereby preventing the spread of the virus. Merck & Co. Inc.'s Isentress (raltegravir) has become a staple in HIV therapy since its approval in 2007. It recorded $1.4 billion in sales for 2011. But that drug has never been co-formulated into a single-drug regimen.

In addition to its Quad application, Gilead also is seeking approval of elvitegravir as a drug in its own right. A separate new drug application (NDA) also is under review for the cobicistat boosting agent, which will compete with marketed boosting agent ritonavir.

The Quad NDA is based on 48-week data from two Phase III noninferiority studies, one pitting Quad against Gilead's own Atripla and one testing the drug against atazanvir/ritonavir plus Truvada in HIV-1-infected antiretroviral-naïve adults. In the first study, 88 percent of Quad patients achieved viral load reduction vs. 84 percent of patients on Atripla. The second study had Quad demonstrating an impressive 90 percent viral load reduction, compared to 87 percent in the atazanvir/ritonavir/Truvada arm. (See BioWorld Today, Aug. 16, 2011, and Sept. 21, 2011.)

Its more convenient dosing should allow Quad to steal a portion of the Isentress market. Deutsche Bank's Karnauskas has pointed out that there are roughly 20,000 patients taking Isentress as a first-line therapy, "which is low-hanging fruit for Quad," she wrote in a research note.

There's also potential competition from GSK572 (dolutegravir), a next-generation integrase inhibitor from GlaxoSmithKline plc and Shionogi & Co. Ltd. That drug demonstrated superiority to Atripla last month, with statistical significance driven primarily by discontinuations in the Atripla arm due to adverse event. Full efficacy and safety data from that study have yet to be released, though analysts have pointed to potential cardiovascular risks based on data that cropped up in an earlier dolutegravir study. (See BioWorld Today, July 12, 2012.)

Gilead also expects a first quarter 2013 approval for Quad in the European Union.

While Quad is the next big value driver for Gilead, the firm's hepatitis C virus (HCV) pipeline has been earning its share of headlines. In addition to promising data from its all-oral, interferon-free regimen, Gilead has benefited from disappointing news from competing programs at BMS and Idenix Pharmaceuticals Inc.

BMS scrapped development of BMS-986094 on safety concerns, and the heart and lung toxicity seen with that drug was sufficient to prompt an FDA hold for similar HCV drugs from Idenix. (See BioWorld Today, Aug. 17, 2012, and Aug. 27, 2012.)

Gilead has had less success in expanding its portfolio into the cardiovascular space, most recently terminating a Phase II trial of cicletanin for pulmonary arterial hypertension after a missed endpoint.

Shares of Gilead (NASDAQ:GILD) closed Monday at $57.19, down 10 cents, with the stock bumping up only slightly in after-hours trading.