Maximine + Interferon Update
Reported by Jules Levin

Maxim Pharmaceuticals reported 72 week SVR (sustained virologic response) data for a phase II study of IFN alpha-2b plus Maximine (now called Ceplene). The study is an early evaluation of the feasibility, safety and 4 dose regimens of histamine dihydrochloride (Ceplene) combined with interferon a-2b (Intron-A) in treatment of patients with chronic Hepatitis C previously untreated with IFN.

Rationale For Using Histamine (as explained by Maxim):
The role of Histamine is to reverse the immunosuppression caused by oxidative stress in the liver caused by HCV. Histamine protects Natural Killer and T-cells from inhibition due to oxidative stress, and restores IFN responsiveness.

Sustained Virologic Response (SVR) was defined for this study as <1000 HCV copies/ml (600 IU/ml) using the Cobas Amplicor HCV Monitor Test v 2.0 Roche Diagnostics. 129 patients were randomized and received IFN alpha-2b (3MIU, subcutaneous injection TIW) and 1 of 4 doses of Histamine (3, 5, 6 or 10 mg per week). Patients were treated for 12 weeks, and 118 patients with a virologic complete or partial response were treated for an additional 36 weeks, and followed-up at 72 weeks. This appears like a real limitation of the study: only patients with a complete or partial viral response at week 12 continued treatment for an additional 36 weeks. Another limit of Histamine is that it has to be administered by subcutaneous injection. Histamine administration induced "mild and transient side effects, including transient flush, headache, hypotension, and tachycardia. The authors said the combination was "well tolerated". The authors concluded that the results of the study "suggest that Histamine may improve the efficacy of IFN therapy for HCV".

RESULTS:
At 72 weeks (end of follow-up), combination therapy containing Histamine and IFN a-2b resulted in a sustained virologic response of 40% in all patients (range 37%-44% across 4 arms), 38% with genotype 1 (range 25-50% across 4 arms), and 29% with high viral load (17-43% across 4 arms).

This study appears limited in its ability to show benefit from Histamine. The measure of undetectable viral load used was <1000 copies/ml, while in general studies use <100 copies/ml. As well, at week 12 patients without a complete or partial viral load response were excluded from the study. Previously, it had been announced that a study of Pegasys (Roche pegylated interferon) +histamine was planned.