La croissent

Impaza, an Oral Antibody Therapeutic for Erectile Dysfunction: Benefits from Mono- and Combine Therapy
A. Martyushev-Poklad1, E. Mazo2, S. Gamidov2, J. Dugina1, O. Epstein1 and S. Sergeeva1
1 Materia Medica Holding Company, 2Russian State Medical University, Moscow, Russia

Summary
Impaza (IZ) (antibodies to endothelial NO synthase, ultra-low doses for oral use) is a novel Russiantherapeutic for erectile dysfunction (ED). Its benefits in ED were studied in two controlled randomised clinical trials. In a 12-week placebo-controlled study ED patients received IZ (n=139) or placebo (n=30) (oral tablets, on alternate days). Efficacy was assessed by IIEF and general efficacy question. In a 6-month study, ED patients received sildenafil (SF, n=81), tadalafil (TF, n=64) or IZ (n=73). Innon-responders (evaluated by IIEF) and in side effects, SF or TF were combined with IZ. Efficacy of IZ considerably surpassed that of placebo: average improvement of EF domain of IIEF amounted to 6,3±0,4 vs 1,3±0,8. IZ was most effective in psychogenic and arterial vasculogenic ED. IZ was proved safe in patients taking nitrates. In the open-label comparative study, IZ was less effective than SF andTF: positive response to monotherapy was found in 56,2%, 77,8% and 81,3% of patients, correspondingly. Combination of SF or TF with IZ increased positive response to therapy (up to 90-92%); this also subdued adverse effects of SF, for its lower doses were just as effective. The new antibody therapeutic IZ considerably enhances the scope of ED treatment, both as monotherapy and in combination withphosphodiestherase 5 inhibitors.

Introduction
Despite the multiplicity of factors contributing the decay of erectile function, major pathogenetic categories of erectile dysfunction (ED)
©2005 by MEDIMOND S.r.l. F612C0205

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8th International Congress of Andrology

Figure 1. The impact of impaza on NOS-NO-cGMP pathway (suggested from animal studies).

share a common mechanism:functional insufficiency of peripheral regulatory pathway responsible for erection, “NO synthase – NO – guanylyl cyclase – cyclic GMP” signaling, and first of all, the inadequate NO release [1, 2]. Phosphodiestherase type V (PDE5) inhibitors, the most effective first-line therapeutics for ED, provide a temporary control over this insufficiency in cavernous tissue by targeting “downstream events”of the pathway. However, their influence on “upstream events” is yet not documented. Meanwhile, enhancement or recovery of adequate NO release could be a desirable aim in treating ED of various origin. Impaza (antibodies to endothelial NO synthase, ultra low doses for oral use) is a novel drug approved in 2001 by Russian Health Ministry for treatment of ED. It has been marketed since April 2002. Inanimal studies, impaza was shown to enhance rat male copulative function [3], to have no general and reproductive toxicity. Findings from studies of the drug’s influence on “NO synthase – NO-guanylyl cyclase – cyclic GMP” signaling pathway in cavernous tissue suggest the following mechanisms underlying its peripheral effects in ED (see Fig.1). In male rats, course treatment with impaza increasedthe activity of NO synthases, NO production and cGMP concentrations in cavernous tissues. Here we describe what is known so far from controlled clinical trials about the drug’s benefits and possible place in the treatment of ED.

Seoul, Korea, June 12-16, 2005

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Materials and Methods
Efficacy and safety of impaza in monotherapy and combined therapy of ED was studied in two controlledclinical trials. The first trial performed in 2001-2003 was designed as a prospective, double blind, placebo-controlled, randomised study to evaluate efficacy and safety of impaza in the treatment of ED. Patients were enrolled at four clinical centers in Russia: one in Volgograd, two in Moscow, and one in Saint-Petersburg. After the initial clinical and laboratory examination, male outpatients...