Replicor late breaking HBV and follow-up HBV / HDV clinical data

[sorte]

Replicor discloses late breaking HBV and follow-up HBV / HDV clinical data at AASLD 2016
MONTREAL, Nov 15, 2016 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for chronic hepatitis B and D patients, today presented its preliminary interim analysis from its latest REP 401 clinical trial at the American Association for the Study of Liver Disease (AASLD) during the late-breaking oral abstract session at its annual meeting held November 11-15, 2016 in Boston, U.S.A.,
The REP 401 protocol (NCT02565719) is a randomized, controlled trial assessing the safety and efficacy of its first in class HBsAg release inhibitor, REP 2139 and a REP 2139 derivative with improved plasma and tissue clearance (REP 2165) in combination with tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha-2a (peg-IFN) in treatment naïve patients with chronic HBeAg negative HBV infection.
Control patients receiving peg-IFN + TDF exhibited minimal antiviral response beyond suppression of serum HBV DNA. Patients receiving REP 2139 or REP 2139 in addition to peg-IFN and TDF experienced robust, multilog reductions in HBsAg, increased levels of circulating anti-HBsAg antibodies and serum transaminase flares indicating restored immune response in the liver.
Replicor also presented its complete 6 month follow-up data from the REP 301 protocol (NCT02233075) assessing the safety and efficacy of REP 2139 in combination with peg-IFN in patients with chronic HBV / HDV co-infection. After 24 weeks of follow-up, despite the use of a suboptimal combination regimen, 5/12 patients had no detectable HBsAg and 7/12 patients had no detectable HDV RNA, indicating that functional control of infection has been established in these patients.

[sorte]

here are the direct links to the last 2 presentations:

http://replicor.com/wp-content/uploads/2016/11/Replicor-REP-401-AASLD-2016-LB-7.pdf

http://replicor.com/wp-content/uploads/2016/11/Replicor-REP-301-AASLD-2016-1848.pdf

studyforhope, what you think will be the next Replicor's move ? They will be still looking for more effective Rep formula or they will rather focus on dose and duration of therapy ?

[studyforhope]

I think replicor could not afford to further improve the chem formula, but rather needs to pull through with the current trial for hbv e neg for the next two years.They hope that the 2165 will not have the accumulation issues of the 2139, since breakpoints were installed into the formula.

They might try to move further with the hdv project, since the data look so promising. They probably look for a partner,  but the situation is difficult since hdv is not big business and the need to perform weekly infusions makes marketing such a therapy quite a challenge. In hdv confection they will also need a well powered phase 3 trial, which will be expensive if performed in the USA or EU states.

[Airquake]

I'm not exactly sure what I'm looking at. Can somebody explain? I think the last section talks about hbv/hdv coinfection and this appears to be only less than 50% effective. The DNA reduction may be or is attributed to TDF. A little bit confused on that. Also this is only phase 2 so this won't be available anytime so if that's the cure.

[sorte]

it's 41% which is much better than 3-6% accomplished when using peginf or 1-3% after few years of nucs.
Also notice that they probably choose a patients with relatively high or moderate hbsag and most of them were genotype D which is a bit less responsive to peginf than other genotypes. Also most of those people take nucs for one year only and as we know long term use of nucs may unlock some immune responses. So they choose quite tough group of patients.

[Liverpatient]

Thanks sorte for this fantastic clinical result news. This is the best Christmas gift we could ever get. Let's hope Replicor moves fast to get approval of their drugs.

[studyforhope]

Fascinating data particularly for the follow up on the hdv coinfected patients. 7 out of 12 are still hdv RNA negativ 6 month after stopping therapy, most with a very high anti hbsag antibody.

[studyforhope]

The detailled poster and the oral presentation are both available on the replicor website in full.

[sorte]

studyforhope: do you think 6m follow up is enough to say that they are cured from hdv ? I guess hdv or hcv can not stay dormant like hbv ?

[studyforhope]

Since hdv has no stable reservoir and exists in a dynamic Flux , like hcv, one could hope that 6 month is indeed enough to assume hdv eradication in these patients.

You also need to look at the actual poster data, especially the hbsag antibody levels. They stayed extremely high in five pstients. The remaining two without a high AB level, but neg hdv RNA are truly interesting and we have to keep an eye on the further developments.