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ViiV Healthcare, a collaborative HIV focused venture established by GlaxoSmithKline (NYSE:GSK), Pfizer (NYSE:PFE) and Shionogi & Co (OTC:SGIOF), is seeking approval from the FDA and the European Union for dolutegravir, an integrase inhibitor used for the treatment of HIV. Integrase inhibitors act by preventing the reverse transcribed viral DNA from integrating into the human T cell DNA.

According to The Street, the FDA is slated to make a decision on August 17th, after having fast-tracked the approval process. In this article, I will look at the recent trials supporting dolutegavir and briefly discuss the market potential of this new therapeutic.

Clinical Trials

A number of phase 3 studies have been conducted with dolutegravir, all of which have demonstrated excellent results.

In the SPRING-2 phase 3 study, dolutegravir was compared with an FDA-approved integrase inhibitor, raltegravir, as an addition to the background medication. This study was designed as a non-inferiority study, essentially trying to determine if dolutegravir was at least as effective as raltegravir. The results showed that dolutegravir was at least as effective and safe as raltegravir.

In the SINGLE phase 3 study, dolutegravir (with a background regimen of abacavir and lamivudine) was compared to market leader Atripla, a combination treatment of tenofovir, emtricitabine, and efavirenz, in treatment-naïve adults. Remarkably, the 48-week results showed that the dolutegravir treatment was effective for 88% of patients while Atripla was only effective for 81%. Though not a major difference, the finding is statistically significant. Interestingly, the dolutegravir treatment seemed to suppress HIV RNA much quicker than Atripla (median time to suppression: 28 days vs 84 days), though it is not clear that this leads to any difference in clinical outcomes. Also, the dolutegravir combination was better tolerated than Atripla. ViiV Healthcare is currently conducting a trial testing dolutegravir in a fixed-dose single medication along with abacavir and lamivudine.

In the SAILING phase 3 study comparing once-daily dolutegravir to twice-daily raltegravir in patients resistant to two classes of antiretrovirals, the 24-week interim results suggested dolutegravir may be more effective than raltegravir in this setting.

In all of these studies, dolutegravir has demonstrated fairly remarkable efficacy and safety. The evidence supporting dolutegravir is extremely comprehensive. Although the science is firm, the FDA still has to analyze the documentation and validation of manufacturing processes. Gilead Sciences Inc. (NASDAQ:GILD) was shocked when the FDA rejected elvitegravir as a single treatment for use as part of HIV treatment regimens for those reasons. Once approved though, the big question then becomes, will physicians prescribe it?

Market Competition

One important aspect of HIV care is patient compliance with medications. There has been a major push to develop once-a-day treatments using combination drugs to suppress HIV viral loads and increase compliance. Atripla, the market leading once-a-day combination treatment, generated $3.22 billion in sales for Gilead in 2011. Gilead is far and above the market leader for HIV treatments, having acquired a nearly 40% market share, largely lead by Atripla. Although ViiV Healthcare is investigating dolutegravir in a fixed-dose combination treatment, this data will not be available during this FDA filing. Though, based on the SINGLE trial, it is unlikely there will be any scientific problems getting this treatment approved.

Once approved, dolutegravir will be the third integrase inhibitor on the market. Raltegravir, developed by Merck & Co, was the first integrase inhibitor to receive FDA approval back in 2007. In 2009, its indication was expanded from treatment resistant patients to all patients. It has since been approved for pediatric use and even comes in chewable pill form for young children. In 2011, Merck reported worldwide sales of $1.4 billion on raltegravir.

Elvitegravir, another integrase inhibitor, this one being developed by Gilead Sciences which licensed it from Japan Tobacco, was approved by the FDA in 2012. Elvitegravir is marketed as a fixed dose combination pill along with cobicistat, emtricitabine and tenofovir. This combination is called Stribild. In the first quarter of 2013, after being approved in the US in late 2012, Stribild sales reached $92 million. Analysts estimate that Stribild sales could surpass $2 billion by 2015.

This late entry to market may end up being a significant disadvantage for dolutegravir. Dolutegravir has a convincing argument given its strong supporting data. However, physicians will likely be reluctant to change a patient's treatment if they are achieving viral suppression and tolerating the drugs. With so many other highly effective treatments beating dolutegravir to the market, it may have trouble finding its niche.

ViiV Healthcare currently has a portfolio of 10 approved medications for HIV treatment that generates nearly $2 billion in sales annually. GSK owns a 76.5% stake in ViiV Healthcare, while Pfizer claims 13.5% and Shionogi takes 10%. If dolutegravir, particularly as a combination treatment, is able to break into the billion dollar blockbuster range, this will help provide stability in GSK's sales for years to come. However, even if dolutegravir becomes a blockbuster drug, it is unlikely that dolutegravir alone will be able to reverse the trend of declining revenues (a drop of nearly 7%) which has plagued GSK over the past three years. Though with 8 approvals in U.S. or EU and 6 more filings since the start of 2012, and 14 new drugs anticipating completion of phase III trials in 2013 and 2014, GSK may be poised for resurgence.

Source: ViiV Healthcare Partnership Anticipates New HIV Treatment Approval