BioWorld International Correspondent

Belgian firm Innogenetics NV is planning to move its candidate hepatitis C therapeutic vaccine into a full-scale Phase II trial, following the completion of a Phase IIa open-label extension study that yielded promising liver histology data and indicated a cessation in the progression of liver fibrosis in patients with chronic HCV infection, most of whom had failed to respond to current therapy.

The news lifted the Ghent-based company's share price by 28 percent to €11.32 during trading on Nasdaq Europe Thursday. It held on to most of those gains during early trading this week.

Thirty-four of the 35 patients who had participated in the company's initial Phase II trial in 2001 re-enrolled for the follow-up. In the original study, 26 patients had received five 20-microgram injections of the vaccine over a 24-week period, while nine had received placebo. In the follow-up, all 34 participants received six 20-microgram injections of the same vaccine at three-week intervals. Thus, 25 patients underwent two courses of vaccination, and 24 of those underwent liver biopsies at the completion of the study.

The baseline and post-treatment liver histology data were scored blindly by Valeer Desmet and Tania Roskams at the pathology department of the University of Louvain. They found that 38 percent of the patients had an improved Ishak histology score, while another 41 percent had a stable score. On average, the progression of liver fibrosis was completely halted in the study group. The histologic data correlated strongly with patients' immune responses to vaccination and with a decrease in serum levels of the enzyme alanine aminotransferase, which is a marker for liver damage.

Significantly, a large majority of the patients who completed two vaccination courses did not respond to current treatment. "Eighteen of the 24 patients had received interferon-based therapy in the past and had failed to respond to that treatment," Innogenetics Vice President of Medical Affairs Frank Hulstaert told BioWorld International.

The alum-based vaccine, which is produced recombinantly, is based on a consensus sequence of the E1 envelope protein derived from clinical HCV isolates. The company chose this antigen because of its relatively high degree of conservation and its immunogenicity. "We have seen that responders to interferon tended to have higher levels of antibody to E1," said Innogenetics CEO Philippe Archinard.

Innogenetics now aims to move quickly into a Phase II study involving some 100 participants, while it also will continue working with its current treatment group. That program has not been partnered out, and the company is not looking for any takers just yet. "We have the luxury of being able to self-finance the development," Archinard said. The company exited the second quarter with €46.8 million in cash. While it is open to attractive deals, its preference is to complete a full Phase II package before entering an agreement, he said.

Innogenetics already has one other drug candidate in Phase II trials. Its wholly owned subsidiary, XCELLentis, also of Ghent, recently commenced a Phase II multicenter study of LyphoDerm, a preparation of freeze-dried cultured human keratinocytes, in 180 patients with chronic hard-to-heal venous leg ulcers. Innogenetics has additional preclinical programs in pulmonary edema and sepsis, and a diagnostics business that is approaching break-even. The company reported a net loss of €5 million for the first half of the year, on sales of €33 million.