BioWorld International Correspondent

Claiming a first for a therapeutic vaccine in the treatment of hepatitis C virus (HCV) infection, Intercell AG obtained proof-of-concept data in a Phase II clinical trial of IC41-202 and now is looking to combine the product with that of its strategic partner Novartis AG in a prime-boost strategy.

In an interim analysis of the first 25 of 50 treatment-naive HCV patients recruited into the open-label study, a 40 percent reduction in viral load was seen, a statistically significant result. In a subgroup of 12 patients with a high viral load - defined as greater than 2 million viral particles per milliliter of blood - a 60 percent reduction in viral load was observed.

"It's the first time we have seen a sustained, marked effect on viral load reduction," Alexander von Gabain, co-founder and chief scientific officer of Vienna, Austria-based Intercell told BioWorld International. The treatment also attained secondary endpoints of safety and T-cell responses.

Although not sufficient to offer therapeutic benefit to patients, the data offer a development pathway for Intercell, which has been working on an HCV therapeutic vaccine since its foundation. "When ribavirin was developed seven to 10 years ago as a standalone therapy, it didn't show more than a 20 percent reduction in viral load," von Gabain said.

The protocol in the latest study was amended to increase the number, frequency and route of immunization. The biggest decline in viral load was seen two weeks after the eighth and final injection. "We saw in the past, viral reductions which were encouraging, but what was our dilemma was this was transient and in the middle of treatment," von Gabain said.

The vaccine comprises five synthetic peptides harboring HCV and T-cell epitopes, as well as the adjuvant IC30, which consists of poly-L-arginine. Since embarking on the development of IC41, Intercell has developed a newer, more potent adjuvant, IC31, which has a more powerful effect on T-cell induction than IC30. It hopes to be able to substitute IC30 with IC31 in future studies.

"I'm pretty confident that regulatory authorities will allow us without big toxicity studies to exchange the existing adjuvant with the novel adjuvant," von Gabain said. The newer adjuvant already has entered the clinic, in a Phase I clinical trial of a tuberculosis vaccine Intercell is developing with the Statens Serum Institut, of Copenhagen, Denmark.

IC41 was included in the major alliance Intercell entered with Basel, Switzerland-based Novartis last month. The latter also inherited an HCV vaccine development program as part of its acquisition of Emeryville, Calif.-based Chiron Corp. Based on the HCV envelope proteins E1 and E2, plus the synthetic adjuvant MF59, it elicits a B-cell response. "If you take everything together, they are nicely complementary approaches," von Gabain said. The two companies are in discussion about how to take the joint program forward, although it could take another five years to obtain a product approval.

The scope for a product is large. Just 10 percent of the global population of 170 million HCV patients take the current standard therapy, ribavirin plus interferon. And only around half of those obtain benefit, he said, while the side effects are severe.

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