Viiv Healthcare Ltd., a joint venture formed in 2009 by Glaxosmithkline plc (GSK), of London, and New York-based Pfizer Inc. to focus on HIV medicines, garnered its first win with the FDA's approval of dolutegravir.

Branded Tivicay, the next-generation integrase inhibitor in HIV-1 was developed in partnership with Shionogi & Co. Ltd., of Osaka, Japan, which joined Viiv as a 10 percent shareholder in October 2012.

The FDA granted a broad label based on data from four adult Phase III studies and one study in children 12 and older, approving Tivicay for use in both treatment-naïve patients and previously treated HIV-infected adults, including those treated with other integrase strand transfer inhibitors. The drug was approved for children 12 years and older weighing at least 40 kg (approximately 88 pounds) who are either treatment-naïve or previously treated but without integrase strand transfer inhibitors.

Approved ahead of its Aug. 17 PDUFA date, Tivicay is an integrase strand transfer inhibitor that interferes with one of the enzymes necessary for HIV to multiply. The drug represents the first legitimate competitor to the formidable HIV franchise crafted by Gilead Sciences Inc., including four-drug, single-tablet Stribild, which combines the ingredients of Truvada (emtricitabine/tenofovir disoproxil fumarate) plus elvitegravir and boosting agent cobicistat. Approved by the FDA in August 2012, Stribild has nearly a year of commercial sales under its belt, generating $99 million in second-quarter revenues for Foster City, Calif.-based Gilead. (See BioWorld Today, Aug. 28, 2012, Aug. 29, 2012, and July 29, 2013.)

Formulated as a 50-mg tablet that does not require a boosting agent, Tivicay is designed for daily use in combination with other antiretroviral drugs and can be taken with or without food, at any time of the day. The drug, which will be manufactured by GSK, is expected to be available in pharmacies within two weeks.

Bill Collier, the head of North America for Middlesex, UK-based Viiv, said the company's focus on HIV has enabled it "to really understand the unmet needs in HIV, be it from a physician, a patient or a payer point of view. We strongly believe that new options still are needed."

He cited data suggesting that one-third of individuals with HIV in the U.S. are dissatisfied with side effects they experience from current medications.

"We're very confident that we're providing physicians with a broad set of data to be able to help patients who are living with HIV in the United States – and beyond, ultimately," Collier added.

Viiv priced Tivicay at $1,175 per month – a slight premium to the boosted elvitegravir component of Stribild, observed Wells Fargo Securities LLC analyst Brian Abrahams. "Although insurers rarely intervene over drug choices in HIV, this still would limit any potential cost advantages of using Truvada+dolutegravir instead of Stribild," he wrote in a comment.

"We've priced the product, we think, very fairly," Collier told BioWorld Today, with Tivicay positioned higher than Isentress (raltegravir, Merck & Co. Inc.) but "a lot less than boosted protease regimen," enabling competitive pricing for a typical HIV regimen that would include GSK's Epzicom or another backbone drug.

'Greater Potency' and 'Cleaner Safety'

In a research note, Jefferies (Japan) Ltd. analyst Naomi Kumagai predicted sales of Tivicay could explode, topping $2 billion in 2017 and reaching $2.7 billion in 2018. Shionogi is set to receive a flat, high double-digit royalty on sales.

Abrahams was less bullish but conceded that "the agent's favorable properties make it worth watching as a potential competitive threat over the much longer term."

Collier declined to offer Viiv's sales projections for the drug.

The race is now on to see how quickly Tivicay can gain traction against Stribild, Truvada and Gilead's other single-tablet HIV regimens, which also include Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate), Viread (tenofovir disoproxil fumarate) and Complera/Eviplera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate).

Inroads against Atripla – which so far remains the market-leading therapy in Gilead's HIV arsenal – or the company's other HIV drugs would certainly dent revenues. Atripla accounted for $938 million in Gilead's second quarter sales. Investors apparently were not alarmed; Gilead's shares (NASDAQ:GILD) gained 3 cents Tuesday to close at $58.93 in light volume.

Last year, dolutegravir (formerly GSK572) demonstrated superiority to Atripla. In the double-blind, double-dummy Phase III (SINGLE) study of dolutegravir vs. Atripla in treatment-naive adults with HIV-1 infection, 88 percent of patients receiving dolutegravir with Kivexa/Epzicom (abacavir/lamivudine) were virologically suppressed, compared to 81 percent on Atripla. The study enrolled 833 participants, with 414 receiving dolutegravir plus Kivexa/Epzicom and 419 receiving Atripla. (See BioWorld Today, July 12, 2012.)

Undetectable HIV-1 RNA (< 50 c/mL) at 48 weeks was the goal and primary endpoint of the study. Discontinuation rates were 2 percent in the dolutegravir arm and 10 percent in the Atripla arm.

In all, the four Phase III trials evaluating dolutegravir in adults enrolled 2,557 participants, who were randomly assigned to Tivicay or Isentress, each in combination with other antiretroviral drugs, or Atripla. In addition to SINGLE, the Phase III program included a second trial (SPRING-2) in treatment-naïve patients plus the SAILING study in treatment-experienced patients who were failing on current therapy but had not been treated with an integrase inhibitor and VIKING-3 in patients resistant to multiple classes of HIV drugs, including integrase inhibitors.

In short, the studies showed dolutegravir offered "greater potency vs. other integrase inhibitors and cleaner safety," Abrahams wrote in a research note, "without the need for boosting."

A fifth trial established the pharmacokinetics, safety and activity of Tivicay as part of regimens for HIV-infected children. Viiv continues to collect data that could potentially expand the medication's use in the pediatric population.

Along with its new drug application to the FDA, Viiv simultaneously submitted regulatory filings to the European Medicines Agency and to Health Canada in December 2012, and applications are being considered in other countries.

Viiv also plans to submit regulatory filings this year to support a fixed-dose combination of Tivicay and Kivexa/Epzicom, according to Collier.