The Story Behind Sugammadex’s Success

Few medical breakthroughs have been as transformative as Sugammadex. This remarkable drug, developed by the Dutch pharmaceutical company Organon, represents a significant milestone in anesthesia management, particularly in reversing the effects of neuromuscular blockade.

The journey of Sugammadex began with the quest to address the limitations of traditional methods for reversing muscle relaxation induced by anesthesia. These methods often involve lengthy processes with unpredictable outcomes and potential side effects. Recognizing the need for a safer, more efficient solution, researchers turned their attention to cyclodextrins.

Cyclodextrins are a family of cyclic oligosaccharides characterized by a hydrophobic interior and a hydrophilic exterior. Their unique structure enables them to encapsulate guest molecules, forming inclusion complexes. This property intrigued scientists, leading to the exploration of cyclodextrins as potential candidates for reversing neuromuscular blockade.

Among cyclodextrins, gamma-cyclodextrin emerged as a promising candidate due to its ability to encapsulate the neuromuscular blocking agents rocuronium and vecuronium. Building upon this discovery, Organon researchers synthesized Sugammadex, a modified gamma-cyclodextrin specifically designed to encapsulate rocuronium and vecuronium with high affinity.

The first occurrence of Sugammadex in the scientific literature can be traced back to a pivotal study published in 2001. This groundbreaking research, titled “Org 25969, a Novel, Specific Reversal Agent for Rocuronium-Induced Neuromuscular Blockade,” was conducted by researchers from Organon, the pharmaceutical company that developed Sugammadex.

In this study, the authors introduced Sugammadex, then known as Org 25969, as a novel reversal agent for rocuronium-induced neuromuscular blockade. They demonstrated its efficacy in rapidly and effectively reversing the effects of rocuronium, a commonly used neuromuscular blocking agent during anesthesia. This publication laid the foundation for subsequent research and clinical trials that ultimately led to the approval and widespread adoption of Sugammadex as a critical tool in anesthesia management.

Since its initial introduction in scientific literature, Sugammadex has been the subject of numerous studies, reviews, and clinical trials, further validating its efficacy and safety in clinical practice. Its discovery marked a significant advancement in anesthesia pharmacology and continues to benefit patients undergoing surgical procedures worldwide.

The development of Sugammadex was not without challenges. Regulatory hurdles and safety concerns necessitated extensive testing and refinement. However, the perseverance of the research team eventually paid off, culminating in the approval of Sugammadex for clinical use in various countries.

The impact of Sugammadex on anesthesia practice cannot be overstated. Its rapid and reliable reversal of neuromuscular blockade offers numerous advantages, including shorter recovery times, improved patient safety, and enhanced control for medical professionals. By streamlining procedures and minimizing risks, Sugammadex has revolutionized anesthesia management, setting a new standard of care in the field. Currently, it is a blockbuster drug marketed by MSD and developed by dozens of generic companies.

In summary, Sugammadex represents the convergence of scientific ingenuity, perseverance, and innovation. Its development underscores the pivotal role of cyclodextrins in drug discovery and highlights the transformative potential of research-driven solutions in improving patient outcomes.

Would you like to learn more? Here are some great sources to start with!

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Preclinical pharmacology of sugammadex

EMA submission document

Sugammadex – A revolutionary drug in neuromuscular pharmacology

Adamgammadex vs Sugammadex

Check out this fascinatnig discussion on next future of cyclodextrin-based antidotes and scavengers by J Robert Sneyd adn Jennifer Hunter.

Spoiler alert: Phase 3 clinical trials suggest that Adamgammadex is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex.

If you are also thinking about creating a special cyclodextrin like that, this may be useful for you: Custom synthesis of cyclodextrins – www.carbohydesolutions.com

Is adamgammadex the brother of sugammadex or the next generation of reversal agent? – British Journal of Anaesthesia (bjanaesthesia.org)

LSU Health Shreveport and CarboHyde collaborate to develop cyclodextrins for restoring sulfide in various disease conditions

Dr. Chris Kevil’s laboratory at LSU Health Shreveport (LSUHS) has discovered that a clinically approved cyclodextrin-based drug called Sugammadex can act as a hydrogen sulfide donor that restores vasoactive hydrogen. This innovation has already gone through initial in vivo testing with promising results.

To take the next leap in development, LSUHS and CarboHyde will start a multiple-staged collaboration project to assess the effects of various cyclodextrins as potential hydrogen sulfide (H2S) donors in methamphetamine-mediated vascular diseases and for various other cardiovascular diseases. Methamphetamine users face a significantly higher risk for cardiovascular disorders, according to a major study published by the Journal of the American Heart Association earlier this year. The Kevil lab has also recently published that chronic methamphetamine use causes cardiovascular dysfunction due to reduced hydrogen sulfide. This poses an additional threat and possible treatment approach for those who use or have already stopped using meth.

LSU Health Shreveport and the Kevil laboratory will focus on comparing the effects of different cyclodextrin derivatives in blood sulfide levels and test the compounds in vitro and in different animal models. CarboHyde’s expertise will be used to select and customize this project’s best-working cyclodextrin derivatives.

“This is exactly the type of research our minds are formed around. We simply admire innovative ideas and out-of-the-box applications of cyclodextrins and other carbohydrates. We keep looking for opportunities to add our knowledge to drive such studies forward. I am sure our collaboration with LSU Health Shreveport and Dr. Kevil will be mutually rewarding and may open novel insights in the application of cyclodextrins in cardiovascular diseases,” said CarboHyde’s CEO József Tóth about this upcoming collaboration.

“Collaboration with carbohydrate expertise at CarboHyde represents a unique opportunity to develop innovative molecules and modalities to treat methamphetamine and other cardiovascular diseases, said Dr. Chris Kevil.

ABOUT CARBOHYDE

CarboHyde is a private preclinical pharmaceutical start-up company specializing in the development of carbohydrate-based APIs. Our team consists of a small group of seasoned scientists with over 50 years of cumulative experience in the field of carbohydrate chemistry, analysis and pharmaceutical development. The company’s core focus is neurodegenerative diseases, yet we also have other pre-clinical programs in various unmet medical indications. Fully embracing the pharmaceutical development ecosystem, we utilize contract research organizations (CRO) and other companies focusing on CMC and clinical development to make our drug development process efficient. CarboHyde’s management team has extensive experience in medicinal chemistry, marketing, and pharmaceutical development. In addition, CarboHyde is supported by experienced advisers, consultants, and carbohydrate veterans.

ABOUT LSU HEALTH SHREVEPORT LSU Health Shreveport (LSUHS) is one of two health sciences centers of the Louisiana State University (LSU) System and home to one of only 155 medical schools in the nation accredited by the Liaison Committee on Medical Education (LCME). The primary mission of LSUHS is to teach, heal, and discover in order to advance the well-being of the state, region and beyond. LSU Health Shreveport encompasses the School of Medicine, School of Graduate Studies and School of Allied Health Professions, Graduate Medical Education (GME), and a robust research enterprise. More than 1,000 students are enrolled in degree programs at any one time, and nearly 600 residents and fellows are enrolled in LSUHS training programs while treating patients at participating sites (hospitals and clinics) throughout north Louisiana.  At the heart of LSU Health Shreveport is a strong faculty that includes a number of nationally and internationally acclaimed physicians and scientists. More than 600 strong, they lead research efforts, educate students, train residents and fellows, and provide primary and specialty care to patients throughout the region. Research is a core aspect of our institution’s mission and values, and LSU Health Shreveport and is committed to fostering collaboration and discovery to advance the knowledge and practice of science and medicine. Faculty, staff and students are actively engaged in research across a variety of biomedical areas that ranges from traditional basic science research in the lab to translational research and testing of new treatment and prevention methods in clinical trials. LSU Health Shreveport is home to six research centers, four of which are designated Centers of Research Excellence by the Louisiana Board of Regents, that concentrate on public healthcare needs of the state and region, including cancer, cardiovascular disease, virology, immunology, neuroscience, and addiction. LSU Health Shreveport has established strong community support and is committed to fostering a culture of diversity and inclusion that promotes mutual respect for all. For more information, visit www.lsuhs.edu