Short Term Immunotherapy Following REP 9AC'-induced HBsAg Seroclearance Induces Durable Immunological Control of Chronic HBV Infection Move back Print add this item to your Itinerary
Mamun Al-Mahtab1, Michel Bazinet2, Andrew Vaillant2
1Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 2REPLICor Inc., Montreal, QC, Canada
Background: REP 9AC' is a nucleic acid-based polymer (NAP) that clears serum HBsAg by blocking HBV subviral particle formation and release. The effect of add on immunotherapy after HBsAg clearance in chronically infected patients receiving REP 9AC' was examined.
Methods: Add on immunotherapy to existing REP 9AC' therapy was initiated in patients who had cleared their serum HBsAg but with persistent serum HBV DNA. Immmunotherapy consisted of thymosin α1 (Zadaxin™) or pegylated interferon α-2a (Pegasys™). Virologic responses were monitored by measuring serum HBV DNA (Roche Cobas™), serum HBsAg and serum anti-HBs (Abbott Architect™).
Results: REP 9AC'-induced HBsAg seroclearance is accompanied by the appearance of anti-HBs and reductions in serum HBV DNA. However, the continued production of anti-HBs in most patients never exceeded 50 mIU/ml and serum HBV DNA levels in most patients persisted in the range of 1000-3000 cpm. Addition of either Zadaxin™ or Pegasys™ to REP 9AC' therapy resulted in dramatic increases in anti-HBs titers with as little as 5 weeks of immunotherapy to levels comparable to or greater than titers observed in healthy patients with a strong vaccine response. Combination treatment was halted in 6 patients after 13 weeks of immunotherapy. In these patients, anti HBs levels are persistently > 100mIU/ml (2 of 6 patients) and > 1000mIU (4 of 6 patients) 4-12 weeks off treatment. HBV DNA levels are also declining off treatment in these patients. Currently, serum HBV DNA levels have reached < 300 cpm (1 patient), < 200 cpm (1 patient) or < 116 cpm (LLOQ) in the remaining 4 patients.
Conclusions: REP 9AC'-induced HBsAg seroclearance appears to potentiate the immunostimulatory effects of either Zadaxin™ or Pegasys ™ in all patients. Short term exposure to immunotherapy in the absence of HBsAg may induce permanent immunological control of HBV infection in most patients.
Dr. Andrew Vaillant, REPLICor Inc. , Montreal , Canada
Assigned in sessions:
07.06.2013, 08:30-17:30, PT-4, HEP B Clinical, Exhibition Hall
REPLICor presents clinical efficacy and toxicology results in patients with chronic hepatitis B with shortterm exposure to immunotherapy after REP 9AC’ induced clearance of serum HBsAg.
14 May 2013, Boston, U.S.A.
Montreal, Quebec – Tuesday , May14th, 2013 – REPLICor has previously undertaken a proof of concept trial to examine the efficacy of REP 9AC monotherapy in patients with chronic HBV infection. A second proof of concept trial is currently underway in patients with chronic hepatitis B (HBV)undergoing treatment with REP 9AC’in combination with Zadaxin™ or Pegasys™.
Efficacy and toxicology results in REPLICor’s proof of concept trials from monotherapy exposure to REP 9AC or REP 9AC’ were disclosed on Tuesday May 14th, 2013 at the 15 th annual TIDES meeting held in Boston, U.S.A.
Both REP 9AC and REP 9AC’ were shown to rapidly and effectively remove HBsAg from the blood of patients with HBV infection. While REP9AC monotherapy led to the establishment of control of infection off treatment in 2/7 patients, the addition of immunotherapy (either Pegasys™ or Zadaxin™) after REP 9AC’ mediated HBsAg clearance led to profound increases in immune function in all patients and in 8 out of 9 patients, control their viral infection has been maintained for 12 – 24 weeks after all treatment is stopped.
Toxicology results from weekly monotherapy exposure to REP 9AC or REP 9AC’ in many cases > 1 year resulted in no observable drug relatedeffects on liver and kidney function or in lipid or hematological function. Major reported symptoms were shown to be related to the development of mineral deficiency likely due to the mineral chelation properties of these compounds and were controlled or prevented with proper mineral supplementation during treatment.
These results show the well tolerated nature of long term treatment with the nucleic acid polymer compounds REP 9AC and REP 9AC’ and further show the promise of achieving well tolerated control of HBV infection withcombination treatments using these agents.
For the 15th annual TIDES meeting:
It is so depressing to know hundreds of millions of people with chronic hbv are being disregarded with such cure. Hepc is so fortunate they are curable. Sometimes back in my mind, i'd rathet have hepc. I had my smiles ready their svr thread.
With rep9ac progress, where are they at the moment? As i keep reading everyday this forum, there are tens to hundreds of people showing up everyday shocked being recently diagnosed just like me. Just for this forum alone. If there is hepa c cure, there must be hepa b cure!
I agree it is quite frustrating waiting for a cure for HBV. We have two effective oral antivirals that can control the infection very well. Interferon offer a cure for some. At the moment, there are various studies into combination therapy using oral antivirals and interferon, the optimal sequence/timing has yet to be determined, hopefully qHBsAg can be used as a guide. But we desperately need a definitive treatment that can cure most HBV patients, preferably without the side effects of Interferon.
Well, as long as there is a higher % chance of cure, int sides would be worth surpassing. HCV patients went through the sides which are more intense as we've known but they long for a cure so they conquer all those sides, knowing that they have a high chance of svr.
How about hbv? what percentage do we have for a cure? Even so, not all could be a candidate for tx. Hope better meds come out real soon. Int is worth a try as long as we got a better med to combo.
The hcv treatment of ribavirin plus peg also works for hbv. Many things work they are just not trying. Believe me it is all business.
Remember I asked here for everybody to sign a petition asking Replicor to release the drug? And also spread links to other forums so everybody signs it? Then we can send all this to CNN for example and other major news networks to get public help. And funding for Replicor to get going.
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