GENT, Belgium, Oct. 17, 2002 (PRIMEZONE) -- Innogenetics (Other OTC:INGTF) today announced the first liver histology results of its E1-based therapeutic candidate vaccine in 24 patients chronically infected with hepatitis C virus (HCV) genotype 1.
Following previously announced phase II results in patients chronically infected with HCV, an open-label study extension was initiated in the spring of 2002. This study involved a cohort of 34 patients given a course of six 20-microgram injections with Innogenetics' candidate vaccine at 3-week intervals administered intramuscularly. These patients completed the initial study and subsequently re-enrolled. Most of these patients previously failed to respond to current standard treatment.
On completion of this study extension, of the 25 patients who received two complete vaccination courses, 24 underwent a liver biopsy. Two internationally recognized expert pathologists scored these biopsies in a blinded manner. For 79% of patients, the overall Ishak histology score either improved or remained stable, as compared to pre-study scores. A histological improvement was seen in 38% of patients. In addition, on average, the progression of liver fibrosis was completely halted in the study group.
Immune response to the E1-based vaccination was significantly correlated with improvements seen in overall liver histology scores, with the improvement in liver fibrosis scores, and with the decrease in serum levels of the liver enzyme alanine aminotransferase (ALT). The E1-treated patients showed a significant decline in serum levels of ALT from baseline. ALT serum levels reflect liver damage, while HCV ribonucleic acid (HCV-RNA) indicates the presence of the hepatitis C virus. No significant decrease in HCV-RNA levels was observed in the blood. In contrast, the quantity of HCV envelope protein present in the liver decreased significantly. Liver histology improvement following therapeutic vaccination can thus be achieved, while HCV-RNA remains detectable in the blood.
According to Professor Dr. F. Nevens, the principal investigator, "Taken together, these liver biopsy results, which were obtained in a rigorously monitored phase II trial, show that the E1-based therapeutic vaccine has the potential to halt disease progression towards liver cirrhosis, and thus demonstrate an anti-fibrotic effect."
Further patient follow-up and maintenance therapeutic vaccinations are being envisaged to examine its disease-modifying effects over the long-term. Additional studies are being planned to confirm these new and promising findings.
The final results of this study extension will be announced, as anticipated, before year-end.
"This breakthrough study outcome strengthens our efforts to deliver what many patients are waiting for: an effective and well-tolerated treatment of their chronic HCV disease. These results underscore our leadership position in the field of hepatitis C vaccine research, and thus confirm the scientific rationale for a therapeutic vaccine approach in the treatment of chronic hepatitis C. Our plans for the next steps in this development program will be finalized in the first quarter of 2003," concluded Philippe Archinard, Chief Executive Officer of Innogenetics.
Notes to Editor
The initial phase II trial started in the spring of 2001 and entailed 35 patients with chronic hepatitis C virus genotype 1. Twenty-six patients received five 20-microgram injections of the E1-protein on alum vaccine at weeks 0, 4, 8, 12, and 24, while 9 patients received placebo at similar intervals. In the spring of 2002, a study extension was initiated in which 34 of the previously enrolled 35 patients took part. All 34 patients received six 20-microgram injections of the same vaccine at 3-week intervals. Thus, 25 patients received two vaccination courses. A total of 24 out of these 25 patients underwent a liver biopsy after the second vaccination course.
To date, the phase II studies have also demonstrated that the therapeutic candidate vaccine is well tolerated as evidenced by the very low dropout rates over a 17-month study period (34 of 35 patients re-enrolled and completed the study extension).
In patients chronically infected with HCV, antibodies to E1 are typically low while the cellular response to E1 is most often not detected. In the phase II study to date, antibody levels were enhanced and T-cell proliferation indices remained increased over the second course of the vaccination in the vast majority of patients treated with the E1-based therapeutic candidate vaccine.
Liver biopsy remains the gold standard to assess liver disease. Histology is the science of examining such biopsies.
The Ishak scoring method was used to evaluate the liver histology. A histological improvement or worsening is characterized by a change of at least two points according to the Ishak scale (i.e. sum of liver inflammation and fibrosis scores). The Ishak score is a widely accepted tool for the semi-quantitative assessment of liver biopsies in therapeutic trials.
Anti-E2 immunostaining was used to quantify the number of liver cells positive for HCV envelope protein. This immunostain is an indication of the amount of virus present in the liver.
Conference call
A conference call covering this press release is organized today, Thursday October 17, 2002 at 15:30 CET, 14:30 BST and 09:30 EST with Philippe Archinard, CEO of Innogenetics and Dr. Frank Hulstaert, Vice President, Medical Affairs.
To attend the conference, please dial +44 20 8240 8242 (Europe) or +1 303 713 7898 (USA).
To hear a replay of the conference, please dial : +44 20 8288 4459, access code: 437852 (Europe) or +1 703 736 7336, access code: 437852 (USA).
About Innogenetics
The Belgian biotechnology company Innogenetics develops innovative therapies in the fields of hepatitis C, immune disorders, and wound care (the latter through its wholly owned subsidiary XCELLentis(TM)). A clinical development program for a therapeutic vaccine against hepatitis C is currently ongoing. Preclinical programs are underway for the development of a prophylactic vaccine against hepatitis C and for treatment of pulmonary edema and sepsis. Clinical programs are ongoing in the field of wound care, based on cultured keratinocytes or their lysate.
Furthermore, Innogenetics is committed to becoming a worldwide leader in high value-added diagnostics (especially "theranostics") focusing on infectious diseases, neurodegeneration, and genetic testing. With its vertically integrated diagnostics activities, Innogenetics is leveraging its intellectual property, know-how, and product offerings through strategic partnerships with leading in vitro diagnostic players such as Bayer and Roche.
Founded in 1985, Innogenetics has been listed on the NASDAQ Europe since November 1996. Innogenetics has its headquarters in Gent, Belgium, and currently employs 600 staff.
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