EASL - Merck And AbbVie Do Their Best To Topple Gilead

Includes: ABBV, GILD, MRK
by: EP Vantage

Gilead is still the top dog in hepatitis C therapy – but it’s not for want of trying on the part of its competitors. Merck & Co (NYSE:MRK) and AbbVie (NYSE:ABBV) both presented data at the EASL meeting on compounds that, while unlikely to topple Gilead (NASDAQ:GILD), certainly make the field more interesting.

The newest entrant, Merck, reported that its combination tablet Zepatier (grazoprevir/elbasvir) beat Gilead’s Solvadi on both efficacy and safety in a head-to-head phase III trial in patients with HCV genotypes 1 and 4. However, it was a pyrrhic victory for Merck, according to Leerink analysts, who pointed out that the comparator arm “is no longer a state of the art, or even widely used or recommended treatment for patients with genotype 1 or 4 HCV”.

Disappointing launch

Zepatier was approved in January and priced at a significant discount to Gilead’s newer doublet Harvoni, but has so far failed to take the hep C world by storm (Looking for a hep C price war? Merck just started it, January 29, 2016).

The drug’s early trajectory was significantly lower than that of AbbVie’s Viekira Pak, the third biggest seller after Gilead's Harvoni and Sovaldi, “and shows no signs of an inflection or acceleration”, noted the Leerink analysts in March.

It has not been helped by the fact it is less effective in patients with NS5A resistance-associated variants, meaning testing for these variants is recommended before treatment begins, which could put doctors off prescribing it. Maybe the latest results will give Zepatier a boost.

Similarly, AbbVie has not managed to hurt Gilead since the launch of Viekira Pak in 2014, but real-world registry data presented at EASL have produced impressive results, with 96% of genotype 1 and 100% of genotype 4 patients responding – supporting the drug’s use in a diverse patient population including previously treated patients, or those with cirrhosis.

AbbVie also reported results with its next-generation combo ABT-493/ABT-530 from the ongoing phase II Magellan-1 study in genotype 1 patients who have failed on previous therapy. The first part of the trial found that combining the drug with ribavirin led to a 12-week sustained virologic response (SVR12) rate of 91%; this dropped to 86% when ribavirin was not included.

Gilead goes for the triple

However, the Leerink analysts do not seem to think that ABT-493/ABT-530 poses a threat to Gilead’s franchise. The latter is already well ahead with its triple combination, sofosbuvir/velpatasvir/GS9857, and had two presentations at EASL supporting its use in patients who have failed prior therapy.

The first concerned a phase II study in 49 genotype 1 patients that found an overall SVR12 rate of 98%. The second presentation combined the results of two phase II trials in genotypes 1-6, and reported a SVR12 of 99%.

Gilead is currently studying a 12-week course of the triplet, but it could bring the treatment duration down to eight weeks. Four pivotal trials of the agent are set to read out in 2017, and if they replicate the “impressive efficacy” in phase II, the drug is likely to be approved and become the gold standard for refractory patients, the Leerink analysts wrote.

One thing to watch out for will be gastrointestinal side effects, which were seen in phase II. This could mean that the triple combo is reserved as a rescue treatment for patients failing on Harvoni or Gilead’s new doublet, sofosbuvir/velpatasvir, which has a PDUFA date of June 28.

Despite its rivals’ best efforts, Gilead seems set to keep its stranglehold on the hep C market.

Drug(s) Trial name Stage ID
Zepatier vs Solvadi + peginterferon and ribavirin C-Edge head-to-head Phase III NCT02358044
ABT-493/ABT-530 Magellan-1 Phase II NCT02446717
Sofosbuvir/velpatasvir/GS-9857 N/A Phase II NCT02536313
Sofosbuvir/velpatasvir/GS-9857 GS-US-367-1168 Phase II NCT02378935
Sofosbuvir/velpatasvir/GS-9857 GS-US-367-1169 Phase II NCT02378961
Sofosbuvir/velpatasvir/GS-9857 Polaris-1 Phase III NCT02607735
Sofosbuvir/velpatasvir/GS-9857 Polaris-2 Phase III NCT02607800
Sofosbuvir/velpatasvir/GS-9857 N/A Phase III NCT02639247
Sofosbuvir/velpatasvir/GS-9857 N/A Phase III NCT02639338

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