Drug & Device Development

Immune activator may make interferon-alpha more potent as HCV treatment

Last Updated: 2007-09-18 18:46:27 -0400 (Reuters Health)

By Deborah Mitchell

CHICAGO (Reuters Health) - A novel immune system activator that induces high and sustained levels of endogenous interferon-alpha is about to undergo phase I testing in patients with chronic hepatitis C (HCV) infection, scientists reported Monday at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy

The drug candidate is a toll-like receptor (TLR) agonist, called IMO-2125, developed by researchers at Idera Pharmaceuticals, Inc. in Cambridge, Massachusetts.

In preclinical trials, lead investigator Dr. Tim Sullivan and his colleagues at Idera have demonstrated that IMO-2125 induces persistent high concentrations of chemokines and cytokines, including interferon-alpha, in human immune cell cultures and in monkeys.

"By being an agonist of TLR9, this compound will induce an endogenous immune response that includes all of the isoforms of interferon-alpha, rather than a single protein, such as the recombinant interferon alpha does," Dr. Sullivan told Reuters Health.

"The main message is that an endogenous interferon-alpha response will result in a broader TH-1 cytokine profile that we expect will have broadly based antiviral activity versus a single protein," Dr. Sullivan added.

Other researchers have reported that different isoforms of interferon-alpha can have varying antiviral activity, he continued. "I believe we also might find that different individuals will respond differently to a single interferon protein."

The new agent also builds a broader based innate immune response that can "bridge to an adaptive immune response," he said. "We have increased antigen presentation capabilities, activated dendritic cells and...proliferation of B cells as well."

IMO-2125 did not interfere with ribavirin, and no adverse effects were observed in studies with rats and monkeys. A similar compound has been used in an oncology setting, and no toxicities or unexpected side effects have been observed so far.

The researchers anticipate that the TLR agonist approach has the potential for use against other types of infection as well.

A phase I trial will test the efficacy of IMO-2125 in subjects with chronic HCV who have not responded to previous treatment or have not had a meaningful reduction in HCV RNA load after 12 to 24 weeks of combination pegylated interferon alpha and ribavirin.

The target enrollment will be 40 patients, who will be separated into four groups of 10 subjects, Idera Pharmaceuticals announced in a statement. Each of the four cohorts will receive different IMO-2125 doses, and two patients in each group will be give placebo. The first patient began treatment September 17, 2007.