The overarching goal at OPERM is to identify and develop promising approaches to nonsurgical permanent contraception (NSPC), and to obtain regulatory approval for new methods of appropriate for use in all clinical environments including low resource settings. To be widely accepted, we have proposed a target product profile with minimum specifications for new methods: near 100% efficacy, safe, applicable to all women who have completed their desired family size, suitable for administration by a non-surgeon healthcare worker, no requirement for surgical facilities, highly stable for shipment and storage in target regions (South Asia, Sub-Saharan Africa) with no cold chain requirements, and inexpensive. In other words, we seek to develop an approach to NSPC appropriate and accessible for use in all women worldwide who desire a permanent method.
Having evaluated novel approaches and early phase concepts from both intramural and extramural investigators, we are now focused on further developing and advancing to human studies our most promising approach: transcervical delivery of polidocanol foam to induce tubal occlusion. In parallel, recognizing the inherent risks associated with clinical product development, we have identified and are investigating several alternative approaches in preclinical studies.
Lead Approach: Targeted transcervical delivery of polidocanol foam
Polidocanol has long been used as a sclerosing agent, and two products (Boston Scientific’s Varithena and Merz Aesthetics’ Asclera) are currently approved to treat varicose veins and venous leg ulcers, with the formation of scar tissue as the underlying mechanism of action for both therapies.
Our lead approach takes advantage of the same scar formation strategy to occlude the fallopian tubal lumen and epithelium as a form of permanent contraception. Results from our previous studies using various forms, concentrations, and dose regimens of polidocanol (solution or foam, with or without additives), have shown that polidocanol, when delivered transcervically, can indeed replace the tubal lumen and epithelium with a collagen scar. Further, we have now completed two long-term contraceptive studies in baboons that show that transcervical polidocanol foam treatment leads to sustained prevention of pregnancy with few side effects.
Along with our collaborators at the Population Council, we are actively working on several activities that will enable us to submit an investigational new drug (IND) application, including: Development of a novel catheter system to selectively deliver a transcervical dose of polidocanol foam to the fallopian tubes with minimal non-target uptake, development and formulation work required for manufacturing under Good Manufacturing Practices (GMP), preclinical proof-of-concept and dose-finding studies at ONPRC, and toxicology studies that meet Good Laboratory Practices (GLP) compliance to demonstrate safety of the product.
We recognize that drug and device development are inherently risky. Thus, we have identified alternative approaches that can serve as a substitute if we reach a “no-go” decision for polidocanol foam. These alternative approaches may also offer advantages over polidocanol foam as “next generation” technologies.
- Strategies for delivering active sclerosing agents: The goal of this approach is to develop a method with which to deliver highly potent active sclerosants to the fallopian tubes. The selective delivery of small volumes of these agents would fill the intramural fallopian tubes without spillage to the peritoneal cavity.
- Screening of potent sclerosing agents: In parallel with developing systems capable of selective and effective delivery, we are also investigating various sclerosants for their ability to trigger sufficient injury to the tubal epithelium to favor the formation of a collagen scar over re-epithelialization and re-canalization of the tubal lumen.