Therapeutic focus – new combos and genotypes the future in hep C

A look at the hepatitis C treatment landscape in 2020 might alarm Gilead Sciences, with forecasts for its top products Harvoni and Solvadi dropping away rapidly after the current year. But the company can take heart from the fact that there is still an appetite for new drugs, particularly combination therapies, with its GS-9857/SOF/GS-5816 set to lead the sector in five years.

While Gilead dominates the top five in 2020, there is also good news for Merck & Co thanks to its combo contender, grazoprevir/elbasvir (see tables below). One thing that both new products have in common is their potential to target hepatitis C strains other than genotype 1, the only type against which most of the current crop are effective.

This looks like a key consideration for new hep C drugs, as it could broaden the patient populations eligible for treatment. Merck’s grazoprevir/elbasvir can be used in patients with genotypes 1, 4 and 6 while Gilead’s GS-9857/SOF/GS-5816 is being tested in phase II in genotypes 1-6.

Daily dosing

Inconvenience is another factor that could limit sales of some drugs, notably Abbvie’s Viekira Pak. Its annual revenues are not forecast to exceed $2.5bn, well below the peak for the rest of the top five, perhaps owing to its dosing regimen and in spite of a slightly lower price (Hep C price war evolves into value competition, January 20, 2015). 

Viekira Pak’s complicated dosing schedule has caused some to question whether the 90% cure rates seen in clinical trials will be replicated in real life. In the worst-case scenario patients could fail to eliminate the virus and need expensive retreatment.

AbbVie will hope that interim results just reported from the Amber study will go some way towards addressing these concerns. Amber, an independent, real-world – but open-label – study, found a sustained virologic response of 98% at 12 weeks with Viekira Pak, in the patients treated so far.

Top five hep C drugs in 2020
Company Drug Status Forecast 2020 sales ($m)
Gilead Sciences GS-9857/SOF/GS-5816 Phase II 6,104
Gilead Sciences Harvoni Marketed 5,962
Merck & Co Grazoprevir/elbasvir Filed 3,006
Gilead Sciences Solvadi Marketed 2,651
AbbVie Viekira Pak Marketed 2,305

The future will see more combination drugs targeting several hepatitis C genotypes – preferably taken as a single pill.

The next contender to hit the market is likely to be Merck’s grazoprevir/elbasvir combo, a once-daily tablet expected to get the go-ahead in 2016. But this will only have a couple of years before it is eclipsed by Gilead’s GS-9857/SOF/GS-5816.

Gilead’s triple combination includes sofosbuvir, already marketed as single-agent Sovaldi and part of dual-agent Harvoni. With the three products forecast to bring in $14.8bn combined in 2020 alone, the $11bn acquisition of Pharmasset looks to have paid off, and then some.

As well as targeting other hep C genotypes, new drugs would ideally reduce the treatment period, with the ultimate aim of a cure within 30 days of therapy. GS-9857/SOF/GS-5816 is getting closer to this, having shown promising results after six weeks in a phase II trial, but grazoprevir/elbasvir is some way off this goal – the pivotal C-EDGE study evaluated 12 and 16 weeks of treatment.

Selected combination therapies in development in hep C
Company Project Status Approval expected
Merck & Co Grazoprevir/elbasvir Filed 2016
Bristol-Myers Squibb Daclatasvir/asunaprevir/beclabuvir Phase III 2016
Gilead Sciences Sofosbuvir/GS-5816 Phase III 2017
Gilead Sciences GS-9857/SOF/GS-5816 Phase II 2018

Bristol joins late

Another triple combination that could reach the market soon is Bristol-Myers Squibb’s daclatasvir/asunaprevir/beclabuvir, set for approval in 2016. Bristol is late to the hep C party: it had been testing daclatasvir in combination with sofosbuvir five or so years ago, but was beaten to the Pharmasset deal by Gilead, forcing it to look at other combinations.

However, it is not clear what advantages Bristol’s combo, which it calls DCV-TRIO, has over the likes of Harvoni. The phase III Unity-2 trial of DCV-TRIO, although promising in terms of cure rates, enrolled genotype 1 patients with a 12-week therapy regimen (Bristol-Myers misses out again in hep C, November 27, 2014). 

And analysts differ wildly on the potential for Bristol’s hep C franchise: Deutsche Bank forecasts sales of $1.8bn by 2019, but Leerink expects $490m the same year.

On the plus side for the company, daclatasvir was recently approved in the US and Europe as Daklinza – in combination with Sovaldi – in genotype 3 disease, the second most common type, affecting around 12% of patients.

But, for the next five years at least, it looks like Gilead will still be dominating the hep C market. Nevertheless, it is wise to plan ahead, and many investors assume that Gilead's recent $10bn debt raise will be used for acquisitions to diversify the group away from hep C.

That said, if Gilead's triple combination lives up to expectations it will make it even harder for other hep C players to take its crown.

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

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