UA Research, Collaborative Efforts on Scorpion Antivenom Lead to FDA Approval

First FDA approval for scorpion antivenom
TUCSON, Ariz. -- The U.S. Food and Drug Administration today approved Anascorp®, an antivenom produced in Mexico and tested in clinical trials conducted through the University of Arizona, for use in treating patients suffering the effects of scorpion sting.

Leslie Boyer“This is an historic event,” says Leslie Boyer, MD, director of the UA’s VIPER (Venom Immunochemistry, Pharmacology and Emergency Response) Institute and lead investigator on the clinical trials. “This is the first-ever drug approved for this use by the FDA; the first-ever drug that we are aware of being developed fully in Latin America and subsequently approved by the FDA; the first-ever scorpion antivenom proved effective under controlled clinical trials; and the first-ever antivenom with so few allergic reactions.”
 
This approval also is the culmination of a nearly 12-year collaboration of academic and clinical researchers with partners in business and industry from both sides of the border. Together with Dr. Boyer, a pediatrician and toxicologist at the UA College of Medicine, these entities joined forces to meet a critical and urgent need.
 
In Arizona, which has the highest concentration of dangerous bark scorpions in the United States, about 8,000 scorpion stings occur each year. Several hundred of these result in serious nerve poisoning and require medical treatment. Nearly all of these patients are young children, whose breathing may be severely affected by the effects of the venom. Without antivenom, children stung by scorpions typically require heavy sedation and intensive supportive care and, often, a ventilator.
 
Decades ago, Arizonans had access to a different kind of antivenom that was produced at Arizona State University, but in 1999 the researcher’s approaching retirement put an end to new production. No known replacement existed, and the critical need for antivenom was about to become urgent.
 
It was about this time that a chance meeting with a National Geographic television crew that was studying venomous creatures of Mexico led Dr. Boyer to visit the Cuernavaca campus of the UNAM (National Autonomous University of Mexico), home of the Institute of Biotechnology, where researchers were investigating the effects of a new antivenom made by Instituto Bioclon, based in Mexico City. She soon determined to bring that antivenom to Arizona. 
 
Having witnessed the use of the antivenom in children stung by scorpions in Mexico, Dr. Boyer was certain of the potential for this drug to help children in Arizona. But the safety and efficacy of the product had to be proved to the exacting standards of the FDA.
 
With a grant from the Office of Orphan Products Development of the FDA, a team of UA and UNAM faculty conducted a study of the then-investigational drug in 2004 and 2005 at University Medical Center and Tucson Medical Center in Tucson. The results were dramatic. Recounted in the New England Journal of Medicine, the study showed that the antivenom alleviated the symptoms of nerve poisoning in children following a scorpion sting in a very short time. It also reduced the need for sedative medication dramatically and lowered levels of scorpion venom in the bloodstream.
 
A second study, conducted primarily at the San Carlos Hospital on Arizona’s San Carlos Apache Indian Reservation, confirmed these findings and demonstrated that the treatment could be safely provided in a rural hospital, far from pediatric intensive care.
 
Andreas Theodorou, MD, a UA professor of pediatrics, chief medical officer of University Medical Center and a member of the research team, says, “This antivenom basically takes symptoms away in a very short time. What was a life-threatening disease that would put kids in the pediatric ICU has become, for most of them, an outpatient disease.”
 
In 2004, the state of Arizona supplied additional research funds through the Arizona Department of Health Services and the Arizona Biomedical Research Commission, enabling the UA to expand its study. Instituto Bioclon and U.S. partner Rare Disease Therapeutics, Inc.,of Tennessee agreed to provide the antivenom to qualifying hospitals, while preparing a formal license application to the U.S. FDA.
 
Since then, nearly 2,000 patients in Arizona and Nevada have received the antivenom. Ultimately, these clinical trials brought together 27 Arizona hospitals, one hospital in Nevada and hundreds of volunteer health-care professionals, creating a first-of-its-kind outreach study network capable of conducting clinical trials of a treatment for a rare emergency.
 
The benefits of this cooperative, international effort extend beyond U.S. patients. Alejandro Alagón, MD, PhD, from the Institute of Biotechnology of the UNAM, is an antivenom researcher and adviser to Instituto Bioclon. He notes that this work has helped patients in Mexico, too: “We have been working together to test the Mexican antivenom under United States rules for close to 12 years, learning a lot from the process and learning from each other. This collaboration has really helped us produce a better product. For this project we needed to combine laboratory science, clinical science and a good manufacturer, and we needed to design a good clinical trial.”
 
During the course of the clinical trials, support provided by the UNAM included developing new analytical techniques to measure the venom and antivenom in the blood of Arizona patients. In addition, scientists from the UNAM worked closely with the Bioclon Institute to ensure that manufacturing processes met the U.S. standards.
 
This collaboration among academic and business partners also is poised to have a global impact. The research has attracted attention from numerous countries with venomous creatures that pose problems for people. Among these is Morocco, where Bioclon, assisted by Drs. Boyer and Alagón, plans to begin clinical trials on a similar antivenom to treat stings inflicted by North Africa’s deadly scorpions.
 
“This project owes its success to the hard work and participation of thousands of people,” Dr. Boyer says. The consortium includes representatives of numerous state and federal agencies; multiple colleges and departments at the UA; 27 Arizona hospitals and one in Nevada; three poison control centers – including the UA’s Arizona Poison and Drug Information Center, which once housed the VIPER Institute; nearly 2,000 Arizona families; undergraduate students and graduate students on both sides of the border; ranchers and scorpion hunters; businessmen and factory workers; and academic colleagues on four continents. All played significant roles, Dr. Boyer explains, adding, “The vast majority of these dedicated individuals received no compensation. They did it because it was in the best interest of the children, because it was the right thing to do.”
 
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The VIPER Institute at the University of Arizona studies applied phylogenetics of venom, combining phylogenetic and drug-development resources across international boundaries, resulting in better, more cost-effective medical care for all. More information about VIPER is available at http://viper.arizona.edu/       
 
Please note: Spanish-language media are asked to contact Rebecca Ruiz-McGill to arrange for interviews, 520-621-1878, rrmcgill@u.arizona.edu
 
For information about the UNAM and its role in biotechnology, contact Renato Dávalos, renatodavalos@hotmail.com, 52-55-56221435 (36/37/38).
           
Instituto Bioclon, member of the Silanes group, is a pharmaceutical company located in Mexico City. Founded in 1990, Bioclon has been a world leader in the development and marketing of antivenoms for snakes, scorpions and spider envenomation on three continents. For more information contact Walter García at wgarcia@silanes.com.mx or at www.bioclon.com.mx
Rare Disease Therapeutics, Inc., is the U.S. license holder of Anascorp® and markets the product in the United States. Rare Disease Therapeutics, Inc., is an established biopharmaceutical company focused on development, registration and distribution of orphan products in the Americas as well as globally through a consortium of similarly focused companies. For more information on Anascorp®, contact Jude McNally, Medical Science Liaison, Director, jmcnally@raretx.com, 520-360-7363.