New REP 9AC Clinical Trial, Adding Interferon and Antivirals, Begins in Europe, with comments by Christine M. Kukka, Project Manager, HBV Advocate

— Christine M. Kukka, Project Manager, HBV Advocate

For months, the hepatitis B community has been waiting for updates about the experimental drug REP 9AC that stops production of hepatitis B surface antigen (HBsAg) within weeks. There will be no news unveiled at this week's international Liver Conference in Washington D.C., but a new clinical trial is about to begin that combines REP 9AC with an immune stimulant and an antiviral.

REP 9AC, administered intravenously, uses nucleic acid-based polymers to stop HBV-infected liver cells from releasing HBsAg—an antigen critical to the production of HBV. Early clinical trials in HBV-infected animals and humans showed that within four weeks REP 9AC rapidly reduced or eliminated HBsAg in the blood.

The drug’s developers, REPLICor Inc. based in Montreal, had hoped the dramatic decline in HBsAg would enable the immune system to quickly gain the upper hand and eradicate the infection. However, patients treated with just REP 9AC didn’t clear the infection as anticipated. Despite the decline in HBsAg, in many cases viral load remained detectable and the infection remained entrenched in liver cells.

“In some patients, REP 9AC (by itself) was enough to allow their immune systems to fully recover during the course of about six months of treatment and these patients have long-term control (after four years) of their infection,” Andrew Vaillant, REPLICor’s chief scientific officer and director of operations, wrote in an email to Next, developers tweaked the drug to allow it to be absorbed more easily (the second-generation drug is called REP 9AC’) and tried adding either pegylated interferon (Pegasys) or another immune stimulator, thymalfasin to the ongoing REP 9AC’ treatment to see if the drug combination would knock out the infection.

At the July 2013 meeting of the Asian Pacific Association for the Study of Liver Disease, researchers reported that the number of surface antibodies did rise rapidly in these patients and viral load continued to decline even after treatment ended, but they still were not happy with the result.

In its latest clinical trial, involving 20 patients, researchers will try a triple treatment of REP 9AC’, the immune stimulant and an antiviral (either entecavir (Baraclude) or tenofovir (Viread). “This triple combination will likely provide the most potent response in patients,” Vaillant wrote.

Many patients have been frustrated with the slow pace of REPLICor’s drug development. The company is privately-held and its development pace is so far slower than that of “big pharma companies” that are funded through publicly-traded stock sales.

“We are aware that some patients have been frustrated with the apparent ‘slow’ pace of progress with this technology,” Vaillant told the HBVadvocate, “but we have had to do many things with these initial proof of concept experiments, including optimizing the dosing regimen and tolerability for REP 9AC/REP 9AC’ and understanding how best to use REP 9AC’ in a combination regimen to achieve the best possible sustained viral response result in patients with a defined course of therapy.

“We feel that we are getting to the end of this process and we are hopeful that the European study will be the last confirmatory piece of evidence we will need to start the registration process for this treatment,” he wrote.

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