Gilead Sciences’ dominance of the one- and two-drug hepatitis C antiviral spaces is now complete with the approvals of Harvoni in the US and Europe. Now the race is on to study new combinations as attention turns to shorter treatment duration and wider patient populations.
Harvoni’s massive advantage as the first one-pill once-daily regimen is counterbalanced by its effectiveness in genotype 1 patients only, so Gilead’s first drug, Sovaldi, remains important for patients with three other strains of the virus. Meanwhile, competitors like Johnson & Johnson and Bristol-Myers Squibb have pivoted in recent days to collaborating on three-drug trials in recognition of the swift evolution of hep C medicine.
Harvoni's approval in the US, announced on Friday, has seemed like little more than a formality for some time given its high cure rate and the fact that it is the first pill that will allow patients to avoid use of interferon or ribavirin. As recently as three years ago these were the only drugs available to treat the virus, but their side-effect profile and limited effectiveness meant many patients did not initiate therapy until liver function began to decline.
The label recommends 12 weeks of Harvoni for patients infected with genotype 1 as long as they have never been treated or if they have failed after treatment and do not have cirrhosis. Cirrhotics who have failed treatment previously are recommended for 24 weeks. An eight-week regimen can be considered in non-cirrhotic, treatment-naive patients with lower viral loads.
Sovaldi is effective in genotypes 1 to 4, but in all cases it was labelled for use with ribavirin, and also with interferon in the case of genotypes 1 and 4. The addition of the agent ledipasvir to Sovaldi’s sofosbuvir to create Harvoni clearly limits the patient groupings but offers an improvement in genotype 1, the most common type of the virus.
Thus Harvoni's price – $1,125 per pill – works out to $94,500 for 12 weeks or $63,000 for eight weeks, and constitutes a 13% list-price increase over Sovaldi. But, because it eliminates the need for thousands of dollars’ worth of interferon and ribavirin compared with Sovaldi, Harvoni does not necessarily represent a more costly drug.
Gilead’s sofosbuvir-based hep C franchise is on track to sell $11.9bn this year, peak at $14.2bn in 2016 and retreat to $11bn in 2020. But as newer agents enter the fray the California-based group will need to be nimble with its own pipeline to retain dominance.
The first pressure point will be an FDA decision expected next month on using Johnson & Johnson’s Olysio with Sovaldi in an interferon- and ribavirin-free regimen. This is a combination that is already in use off-label because of strong phase II data revealed a year ago; however, it is pricey as Olysio costs more than $60,000 separately from Sovaldi.
Analysts do not view Olysio’s outlook optimistically: the current consensus puts 2014 as its peak year with $2.3bn in sales. J&J appears to have realised this only recently and has, among other actions, bought the antiviral play Alios (J&J hangs in hep C game with $1.8bn Alios takeout, September 30, 2014). On Friday, hours before the FDA announced the Harvoni approval, a trial of Olysio, Sovaldi and Bristol-Myers Squibb’s Daklinza was announced.
Bristol-Myers’ position is similar with its Daklinza awaiting the FDA’s decision before the year is out. Last week it said it was abandoning combination work with a second agent it owns, asunaprevir, “because of the rapidly evolving hepatitis C treatment landscape”. Given that like Olysio Daklinza has already been tested extensively with Sovaldi, the triple combination ought to be promising, though it has significant cost attached to it.
A second pressure point on Gilead could come as soon as December should the FDA approve the AbbVie combination based around the ritonavir-boosted pill called ABT-450/r/ABT-267 and ABT-333 in genotype 1. This is now figured to be a modest player in comparison with Gilead, with peak sales of $2.7bn in 2016.
AbbVie executives claim they do not plan to compete with Gilead on price, but time will tell whether this is a statement they can live up to.
Thus Gilead must be mindful of the need to keep its own pipeline flowing. It is not short of clinical-stage protease and polymerase inhibitors to plug into new combinations. No new launches are expected for two years, however, so it needs to hope that nothing emerges that represents a step change on its chunky sofosbuvir-based franchise.