EASL – Other hepatitis viruses take the spotlight along with Nash

Hepatitis C may have had its moment in the sun, and now biopharma has turned to other liver diseases. The meeting of the European Association for the Study of the Liver (EASL) beginning on April 19 in Amsterdam will see data in two other forms of viral hepatitis, B and D, from two developers, Gilead Sciences and Eiger Biopharmaceuticals.

Meanwhile, hepatologists will get a better idea of whether the sector’s heavy investment in treatments for non-alcoholic steatohepatitis (Nash) will pay off as Gilead, Bristol-Myers Squibb and Durect are due to present data. And the newly listed Albireo Pharma has been selected for a late-breaking presentation for its phase II trial of A4250 in children with cholestatic liver disease.

All the letters of the alphabet

Hepatitis C will still have a place of prominence, though it will not meet with the breathless anticipation the pre-Sovaldi era. AbbVie will feature data on its combination glecaprevir & pibrentasvir in cirrhotic patients infected with gentoypes 1, 2, 4, 5 and 6; Merck & Co will present on its triplet MK-3682/grazoprevir/ruzasvir in treatment resistant patients; and Achillion and Johnson & Johnson’s new combination AL-335/odalasvir/simeprevir will be the subject of an oral presentation.

But with hep C in contraction mode, investors will be paying closer attention to other conditions, such as hepatitis B. Gilead’s Vemlidy is already approved in hepatitis B – and as part of the HIV combinations Descovy, Genvoya and Odefsey – but the group is keen to tease out the advantages it has over Viread, the older antiviral on which it is based. The Vemlidy approval was based on head-to-head trials showing the two agents to have similar efficacy in reducing patients’ viral load at 48 weeks – Vemlidy has the advantage of lower bone and renal effects.

At EASL Gilead will release data from a study showing improvements in bone mineral density and creatinine clearance after switching from Viread to Vemlidy. A second presentation will show that Vemlidy continued to be statistically similar on virological suppression at week 96 while maintaining a better safety profile.

In hepatitis B Arrowhead’s now shelved RNA-interference projects will also get some attention, with data demonstrating reduction in hepatitis B surface antigen for ARC-520, and safety data in volunteers for ARC-521. Work on those two projects using the intravenous EX1 delivery vehicle was cancelled because deaths in primates would have required more work to rule out risks to humans – in any case, the safety data should provide some evidence that humans were not harmed (Arrowhead back to drawing board after monkey shock, November 30, 2016).

In another form of hepatitis, Eiger is presenting data on the aggressive hepatitis B co-infection hepatitis D. Its agent, lonafarnib, was once tested as a cancer drug, but now has phase II data in combination with ritonavir from the LOWR HDV-1, 2 and 3 trials. The last of these showed that patients were able to take the combination for six months and achieve viral reductions.

Monster Nash

Nash has, of course, been a focus since the investigator-initiated Flint trial of Ocaliva put Intercept Pharmaceuticals on the radar three years ago. Big pharma has been active in this space, but perhaps none has done as much as Gilead, which will present data from three assets at EASL.

Selonsertib is the group’s lead now that it has abandoned simtuzumab, and presentations will include biomarker data from a trial in 72 Nash patients, either as monotherapy or in combination with simtuzumab. Separately, Gilead will feature pharmacokinetic data from combinations of selonsertib, GS-9674 and/or GS-0976.

Meanwhile, hepatologists will get a first good look at Nash data from Gilead’s antiviral rival Bristol-Myers Squibb. Results from a phase II study of ARX618, licensed from Ambryx and carrying the Bristol code BMS-986036, show evidence of decreased hepatic fat fraction, fibrosis and markers of liver injury.

Durect will have phase I safety data in Nash patients from its Nash therapy DUR-928 oral, which also shows signs of positive effects on liver biomarkers.

Several other Nash assets, such as Genfit’s elafibranor, Inventia’s IVA337 and Enanta Pharmaceucials’s EDP-305, will have preclinical data.

Finally, Albireo Pharma, which went public via a reverse takeover of Biodel, earned a coveted late-breaking presentation for data showing a reduction of serum bile acids and pruritis in patients with cholestatic liver disease taking A4250. This candidate is targeting the orphan paediatric disease progressive familial intrahepatic cholestasis – for which it has orphan drug designation – but testing in Nash is also on the cards.

With hep C having a cure and the only questions hanging over it relating to access, innovation in liver disease looks like it will come from elsewhere. Hepatitis B represents a clear unmet need as it affects hundreds of millions worldwide, and Nash is growing in significance as a leading cause of liver transplantation. It is no surprise to see research focusing in these two conditions.

Selected EASL abstracts
Condition Company Project Trial ID Abstract
Hepatitis B Gilead Vemlidy NCT02979613 PS-041
NCT01940341 PS-042
Arrowhead ARC-520 NCT02738008 PS-045
ARC-521 NCT02797522 THU-176
Hepatitis D Eiger lonafarnib NCT02511431 LB-519
Nash Gilead  selonsertib NCT02466516 PS-090
selonsertib/GS-9674/GS-0976 NCT02781584 THU-344
Bristol-Myers Squibb ARX618 NCT02413372 LBO-02
Durect DUR-928 oral n/a SAT-322
Cholestatic liver disease Albireo A4250 NCT02630875 LBO-04
Full abstracts can be accessed here

To contact the writer of this story email Jonathan Gardner in Virginia at [email protected] or follow @ByJonGardner on Twitter

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