Newest Repac Abstract

[Aduiski]

HBsAg and HDV RNA reduction with REP 2139-Ca and peg-INF alpha 2a in chronic HBV/HDV infection.

Nucleic acid polymers (NAPs) inhibit the release of HBsAg and the NAP REP 2139 can efficiently clear HBsAg from the blood of patients with HBV mono-infection. REP 2139-Ca therapy combined with pegylated interferon alpha-2a is being evaluated in Caucasian patients with HBV/HDV co-infection (NCT02233075).
Patients received REP 2139-Ca once weekly for 15 weeks (500 mg) by 2 h IV infusion, followed by combined therapy for 15 weeks with pegylated interferon alpha-2a (180ug SC qW) with 250 mg REP 2139-Ca. Patients then transition to 33 weeks of pegylated interferon alpha-2a monotherapy. HDV RNA, HBV DNA, HBsAg and anti-HBs are followed every two weeks using standard assays (Robogene RT- PCR, Abbott RealTime HBV, Abbott Architect).
On treatment, observed HBsAg reductions are currently *5 logs in 6 patients (all \1 IU / ml), *3 logs in three patients and *0.5 to 1.5 logs in three patients. HDV RNA is currently undetectable in ten patients (*5 to 8 log reduction from baseline) with *3 and *5 log reductions observed in the other two patients. Substantial elevation (389–15,408 mIU/ml) of serum anti-HBs and the development of liver flares were only observed with the onset of exposure to pegy- lated interferon alpha-2a and was only evident in patients with serum HBsAg \1 IU / ml at the start of immunotherapy.
REP 2139-Ca is able to achieve rapid reductions in serum HBsAg and HDV RNA in Caucasian patients with HBV/HDV infection. REP 2139-Ca may become an important new therapeutic option for patients with chronic HBV/HDV infection.

[sorte]

I don't think so cure for hdv may be treated as orphan drug, because it's a lof of people infected to test on. I think we should aim for fast track procedure.

[stef2011]

i dont know fast track. is it requiring little money and small trials for approval?

[studyforhope]

First one needs to await the stability of the HDV CLEARANCE after stopping the treatment. This can only be judged after at least 6 month of follow up.Currently it seems plausible that 5 out of the 11 fully treated patients might have a true SVR for hdv and hbv. But even in these cases we will need to wait and see.

If it is possible  that the currently hdv neg patients that are not expected to stably seroconvert the hbsag will still have selectively lost hdv remains to be seen. It is unlikely and would represent a true sensation if possible.

[sorte]

Small trial is for orphan drugs I think, fast track is:

http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm

I wonder if hdv drug has chance for that procedure ?

[sorte]

So it's 15 weeks on peginf left and than 6 months of observation ?

[studyforhope]

6 month of follow up is barely enough to confirm a stable svr.

I do not b think that any agency will give approval based on 12 patients. They will, for hdv, negotiate a registration trial design with replicor.

BTW the current trial in Moldavia was NOT DESIGNED to achieve a functional cure. It's pupose was to show that  the nap component was independently causing a strong, objective positive effect, BEFORE the interferon overlap.

The new trial, starting now is designed to achieve a functional cure in the hope that a full year of naps plus a simultaneous interferon or thymosin alpha treatment, all combined with TDF and  with a TDF pretreatment period of 6 month,  will achieve hbsag seroconversion in a high percentage of patients.

Those will be e neg patients again, but without hdv.

What is most fascinating is the thymosin alpha arm, since this has almost no side effects compared with interferon and seemed more promising in the second Bangladesh trial than interferon.