Event – US approval could put Glaxo’s dolutegravir at the top of the class

With priority review status, solid clinical data, and having been hailed by some analysts as the best drug in its class, expectations for GlaxoSmithKline’s dolutegravir are blockbuster high. The FDA’s decision on whether to approve it, expected mid-month, means that Glaxo is poised to leap up the rankings in HIV, knocking lumps out of Merck & Co and perhaps Gilead Sciences on the way.

As ever, much depends on the label. Bernstein analysts have been concerned that dolutegravir, also called GSK1349572, may be directed for use in patients who have already failed on other HIV integrase inhibitors, namely Merck’s Isentress. But antivirals are not like antibiotics, and with HIV still one of the most alarming diagnoses a patient can receive, the agency will be under pressure to allow doctors to use their most powerful weapons first.

Company  GlaxoSmithKline Shionogi
Product  Dolutegravir 
Market cap  $128bn $7.4bn
Product NPV  $2.4bn $801m
% of market cap  2% 11%
Event type  PDUFA 
Date  August 16, 2013

Half the market

Dolutegravir’s showing in the clinic has been impressive, proving itself a better virus suppressor than Isentress in patients who had not been treated with an integrase inhibitor (Dolutegravir sailing toward key regulatory dates, March 7, 2013).

This led analysts from Bernstein to state that they believed it to be the best-in-class integrase inhibitor, though they pointed out that despite its success in integrase inhibitor-naïve patients it might come to be used primarily in Isentress failures.

Analysts from Leerink Swann predict rapid declines in Isentress’s market share after launch of dolutegravir – unsurprising given that Isentress is the only integrase inhibitor on the US market at the moment, commanding therefore a share of 100%.

EvaluatePharma’s consensus data suggests that US approval of dolutegravir, and to a lesser extent Gilead’s elvitegravir, will cut Isentress’s share to just 34% in the next five years, though as the market overall will grow 19%, Isentress sales will remain healthy (see table). Dolutegravir itself is predicted to scoop just over half the integrase inhibitor market, with sales increasing by a CAGR of 87% between 2013 and 2018.

Dolutegravir is not solely a Glaxo project. Developed under the auspices of Viiv, Glaxo’s HIV-focused joint-venture with Pfizer and Shionogi, the latter company – dolutegravir’s originator – will get royalties in the high teens on sales of the drug.

Dolutegravir’s reach could be extended further after its approval: Viiv is already trialling it along with its fixed-dose combination of abacavir and lamivudine, branded Epzicom in the US. The combination of all three drugs is currently referred to as 572-Trii or dolutegravir-Trii. Results from the dolutegravir/Epzicom trial are expected this year.

In short, with a safety record as good as or better than Isentress and apparently better efficacy, US approval of dolutegravir looks more or less assured. Approval in Europe is also expected in short order too, and will help propel the drug to blockbuster status.

HIV integrase inhibitors annual US sales ($m)
Product Generic Name Company Current phase  2011 2012 2013 2014 2015 2016 2017 2018 CAGR 2011-2018 2018 market share
Dolutegravir dolutegravir GlaxoSmithKline Filed - - 55 211 432 737 983 1,244 n/a 54%
Isentress raltegravir potassium Merck & Co Marketed 681 822 855 848 836 815 800 780 2% 34%
Elvitegravir elvitegravir Gilead Sciences Filed - - 24 68 122 171 224 278 n/a 12%
Total 681 822 935 1,126 1,390 1,723 2,007 2,302 19%

To contact the writer of this story email Elizabeth Cairns in London at elizabethc@epvantage.com or follow @LizEPVantage on Twitter

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