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Event – Gilead needs to best Glaxo with bictegravir

Date May 16, 2017

With Gilead's hepatitis C franchise fading, HIV is becoming ever more important to the company – making the upcoming phase III results from four studies of its next-generation integrase inhibitor bictegravir critical.

Gilead has a chance to regain momentum and take the fight to Glaxosmithkline, whose rival agent dolutegravir is already taking the HIV market by storm: two of the phase III trials compare bictegravir-based regimens with those containing dolutegravir. Bictegravir needs at least to demonstrate non-inferiority, but superiority would be preferable if Gilead is to halt its slide in market share.

Project  Bictegravir/F/TAF 
Company  Gilead Sciences 
Product NPV  $8.11bn 
% of market cap  10% 
Event  Results from four phase III trials 
Date  Q2 2017 

Both head-to-head studies have been powered on the assumption that the dolutegravir-containing regimens will have a 91% success rate, with the lower bound of the 95% confidence interval set at 12%. This means that as long as bictegravir is no more than 12 percentage points below its comparator it will hit non-inferiority.

Phase II data suggests that this is possible – a phase II trial showed a 97% response rate with a bictegravir-based regimen, versus 91-94% with dolutegravir-based therapy, but the difference was not statistically significant (Gilead and Glaxo’s HIV battle intensifies, February 14, 2017).

If non-inferiority is hit the study design allows for a superiority analysis – and success here would be a real win.

Stifel analysts believe that bictegravir could be the best-in-class integrase inhibitor, pointing out that the small size of the phase II study would have made it hard to reach significance, and highlighting a potentially favourable safety profile.

Gilead must also be confident, having taken the risk of carrying out head-to-head studies, although realistically it had no choice if it wants to grab sizeable market share. Thus these readouts represent a real opportunity to steal a march on its rival – but any slip will put the ball firmly back in Glaxo’s court.

Switching

Two switching studies in treatment-experienced patients are also due to report in the second quarter. The first looks at patients switching from abacavir/dolutegravir/lamivudine – the combination marketed by Glaxo as Triumeq – to bictegravir plus emtricitabine and tenofovir alafenamide, known as F/TAF.

The second trial evaluates patients who had previously been treated with boosted atazanavir or darunavir plus either emtricitabine/tenofovir disoproxil or abacavir/lamivudine. Tenofovir disoproxil is a component of Gilead’s older HIV drugs, which it has been replacing with TAF.

There is also a third phase III switching study, with a primary completion date of September 2017. Gilead plans to file bictegravir for approval in the third quarter.

Unlike older integrase inhibitors, bictegravir and dolutegravir do not require boosting – taking another drug to raise circulating levels – so have a lower risk of adverse events and drug-drug interactions.

Glaxo has the upper hand in this space for now, and is already planning for the future, developing two dolutegravir doublets that could signal an even lower incidence of side effects. Minimising impact on measures like blood glucose and cholesterol levels has become more important as HIV patients live longer, and these readings will be also be scrutinised as the bictegravir trials read out.

A combination of dolutegravir and Johnson & Johnson’s Edurant looks likely to be reach the market next year. But while Glaxo is in a strong position for now, it is acutely aware that this situation could change.

“The difference now is for our main competitor HIV has become again their major growth driver,” David Redfern, chairman of the company’s Viiv HIV business, said during its first-quarter earnings call. “So there's no doubt the competitive intensity is not going down.”

Whether bictegravir is non-inferior or superior, Gilead will be highly motivated to make the most of this opportunity.

Upcoming bictegravir/F/TAF phase III readouts 
Study  Details  Trial ID  Data due 
GS-US-380-1489  vs abacavir/dolutegravir/lamivudine (Triumeq)  NCT02607930  May 2017 
GS-US-380-1490  vs dolutegravir + F/TAF  NCT02607956  May 2017 
GS-US-380-1844  Phase III switching study  NCT02603120  Apr 2017 
GS-US-380-1878  Phase III switching study  NCT02603107  May 2017 
GS-US-380-1961  Phase III switching study  NCT02652624  Sep 2017 

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow  @ByMadeleineA on Twitter

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