RISUG® as a male contraceptive: journey from bench to bedside

Abstract

Even after decades of research men still lack reliable and reversible contraceptive methods comparable to female methods of contraception. Traditional methods of male contraception present a high failure rate and also involve high risk both when used for contraception and for protection against sexually transmitted diseases. Various chemical, hormonal, immunological, vas based and herbal methods of contraception have been examined by scientists world over during the past four decades. Among the possible lead approaches, exogenous hormonal contraception, either alone or in combination with progesterone or antiandrogen, is being viewed at low profile because of their insufficiency in inducing uniform suppression of spermatogenesis and steroid related long term complications. As an alternative to vasectomy, among various intravasal devices being examined, RISUG ® (Reversible Inhibition of Sperm Under Guidance), a co-polymer of styrene and maleic anhydride offers long term contraception with safety, efficacy and it can be delivered by no-scalpel injection. Thus it is the only male contraceptive procedure currently under Phase-III Clinical Trial. The non-invasive reversal technique, successfully demonstrated in langur monkeys and functional reversal achieved with dimethyl sulphoxide (DMSO) and sodium bicarbonate (NaHCO 3) in rats and rabbits with safety at F 1 generation (first filial generation) have projected RISUG ® as a better alternative to vasectomy. In this narrative review we revisit the long journey of RISUG ® beginning with formulation on a bench towards reaching the market as a safe and effective contraceptive method, discussing various milestones and roadblocks of this expedition awaiting the mandatory regulatory clearance from the Government of India. Successful completion of ongoing phase III clinical trials with demonstration of reversal in human volunteers will give an indigenously developed male contraceptive to the world.

Hormonal Male Contraception: Getting to Market

“…A recent review of these approaches has been published (47); major hurdles in advancing development of non-hormonal contraception for men includes ensuring specificity, drugability, safety, and efficacy in animal models. With the exception of trials in India of reversible vaso-occlusion (48), where reversibility remains a major challenge, novel non-hormonal contraceptives for men have not reached clinical trials. It is likely that hormonal male contraceptives will be the first novel, reversible male method to reach the marketplace, hopefully paving the way for additional methods to contribute to the male contraceptive menu going forward.…”

Biomaterial platforms offer capability of efficacious male contraceptives

“…It is applied through a single injection into the vas deferens, and later removed by dissolution at high pH (~8-9) through secondary injection of sodium bicarbonate in DMSO. 9 Although clinical trials suggest significant potential (single injection, complete reversibility, 48 h activation, 96.7% efficacy after six months), limited understanding of the mechanism of action, kinetic control over sterility, and reversal effectiveness has delayed the regulatory clearance of RISUG. 9 Inspired by RISUG, other research groups have offered similar vas-occlusive technologies such as Vasalgel, a poly(styrene-alt -maleic acid) copolymer currently undergoing human trials in the United States, and ADAM™ an aqueous-based platform that is anticipated to begin clinical trials later this year.…”

“…9 Although clinical trials suggest significant potential (single injection, complete reversibility, 48 h activation, 96.7% efficacy after six months), limited understanding of the mechanism of action, kinetic control over sterility, and reversal effectiveness has delayed the regulatory clearance of RISUG. 9 Inspired by RISUG, other research groups have offered similar vas-occlusive technologies such as Vasalgel, a poly(styrene-alt -maleic acid) copolymer currently undergoing human trials in the United States, and ADAM™ an aqueous-based platform that is anticipated to begin clinical trials later this year. Although these platforms are exciting, the technology is relatively primitive considering the vast wealth of knowledge and control materials researchers have over stimuli-responsive biomaterial platforms.…”

RISUG® offers early contraception: An experience during Phase III clinical trials

“…[14] Reversible inhibition of sperm under guidance (RISUG ® ), a copolymer of styrene and maleic anhydride, delivered by no-scalpel injection, offers long-term contraception with safety and efficacy. [15,16] RISUG ® injection is a single intervention procedure in which the polymer is injected into vas deferens through a small incision made in the scrotum, thus avoiding surgery during the initial sterilization procedure. Other major advantages of RISUG ® include no interruption before the sexual act, cost factor, outpatient procedure, and early azoospermia.…”