Merck & Co has high hopes for its hepatitis C doublet grazoprevir/elbasvir, which the FDA is expected to approve on January 28. At the recent JP Morgan meeting the group's chief executive, Ken Frazier, highlighted the product as a key catalyst for 2016.
But analyst excitement is cooling, with 2020 consensus sales forecasts dropping from $3bn in September to just under $2bn currently. And the future could get tougher for Merck’s hep C franchise, with Leerink recently cutting long-term estimates, citing a harder-to-penetrate market. It seems that Gilead is still the company to beat in hep C.
The sector is moving increasingly towards once-daily combinations with shorter treatment cycles that target hepatitis C strains other than genotype 1; Merck is seeking approval for grazoprevir/elbasvir in genotypes 1, 4 and 6 (Therapeutic focus – new combos and genotypes the future in hep C, September 14, 2015).
But, although the FDA nod seems widely expected, many will be closely watching grazoprevir/elbasvir’s label. One potential snag is that it could include a requirement for resistance-associated variant testing for genotype 1a patients, the Leerink analysts write.
Merck will also have to overcome reimbursement issues, with Gilead and Abbvie already locked into long-term contracts with providers with Sovaldi/Harvoni and Viekira Pak respectively.
All this should leave Merck a “distant second” to Gilead, according to Barclays analysts, who believe that the doublet is unlikely to displace Harvoni and Sovaldi. Rather, grazoprevir/elbasvir could find its niche in “certain subpopulation such as co-morbid patients with chronic kidney disease” where it could grab market share from AbbVie and Johnson & Johnson, which markets Olysio.
Grazoprevir/elbasvir might not have long on the market before until another doublet is approved and yet again it is Gilead spoiling the party: its sofosbuvir/velpatasvir, which Leerink describes as “clearly superior”. The combination has shown impressive response rates over 12 weeks in genotypes 1-6 (Gilead sees double in hep C, September 22, 2015); it has a PDUFA date of June 28.
And further along Gilead’s pipeline is a triple combination of sofosbuvir, velpatasvir and the protease inhibitor GS-9857, which is in phase II and could bring the treatment duration down to eight weeks and provide a better option for some hard-to-treat genotype 3 patients, the company believes.
|Selected combination therapies in development in hep C|
|Company||Project||Status||FDA approval expected|
|Merck & Co||Grazoprevir/elbasvir||Filed||January 28, 2016|
|Gilead Sciences||Sofosbuvir/velpatasvir||Filed||June 28, 2016|
|Gilead Sciences||Sofosbuvir/velpatasvir/GS-9857||Phase II||2018|
|Merck & Co||Grazoprevir/MK-8408/MK-3682||Phase II||2018|
Many analysts have not put out forecasts for either Gilead’s doublet or triplet, which are currently likely included in the figures for the company’s existing sofosbuvir-based franchise. But previously some expected that the triplet would become the best-selling hep C drug in 2020.
Merck might therefore be better off focusing on its own triple combination combining grazoprevir with MK-8408 and MK-3682, which has shown potential as an eight-week treatment regimen in phase II and is slated to go into phase III this year.
Lower price, higher volume?
When it comes to future growth, however, one problem could be a shrinking patient pool as sicker patients are cured.
But Gilead executives did not seem fazed about this during the JP Morgan conference. The company's chief operating officer, John Milligan, pointed out that the company had treated over 300,000 patients in the US using Harvoni or Solvadi between December 2013 and September 2015, but around four million are infected. “There’s still a tremendous opportunity ahead of us.”
Gilead expects to see less sick patients being treated, which will expand the market – but prices might need to come down for this to be feasible. However, when asked about the general drug pricing debate, Mr Milligan replied: “I think the opportunity for meaningful change to drug pricing in the US is quite low.”
Gilead seems confident that the clinical profile of its drugs will set them apart, with Mr Milligan adding: “A price action does not necessarily guarantee success.” This was perhaps a swipe at another hep C player, Abbvie, whose Viekira Pak has disappointed in spite of its efforts to undercut the competition.
AbbVie fights back
But AbbVie’s chief executive, Rick Gonzalez, was bullish about its hep C franchise at JP Morgan, highlighting it as one of three key brands. The company is expecting approval of a once-daily formulation of Viekira this year, which should address the original product’s complicated dosing schedule.
It is also developing a next-generation combination of its own, incorporating ABT-493, an NS3/4A protease inhibitor originally developed by Enanta Pharmaceuticals, and ABT-530, an NS5A inhibitor. The combo does not require a ribavirin backbone and could be effective over an eight-week treatment period (AASLD – Pan-genotypic combos test Gilead’s hep C dominance, November 18, 2015).
AbbVie started a programme of six phase III studies earlier this month in patients with genotype 1-6, and expects to start seeing data later this year.
However, while Merck and AbbVie are doing their best to catch up, it seems that Gilead is still setting the pace in hepatitis C.