his is a special guest blog by Jack Facente, director of Agritoxins Venom Labs
Today North America does not have current (in date) FDA approved antivenom for Coral Snake (Micrurus fulvius) envenomations. Wyeth, the only manufacturer of Coral Snake antivenom since 1967, stopped producing the antivenom in 2003. All of the 2003 antivenom lots expired in 2008. As supplies dwindled, the FDA tested and extended Wyeth Coral Snake antivenom lot # 4030026 for use until Oct 31st of 2009. Wyeth Pharmaceutical was purchased by Pfizer in 2009 and Pfizer sought FDA approval to extend lot #4030026 each year until October 31st of 2012. This lot number, while quite effective for envenomation treatment, was running low. On December 7, 2012, Pfizer sent out a letter to the North American Health Care Providers (Hospitals) extending a second lot #4030024 (that also expired on October 31, 2008) until April 2014. With less than 100 envenomations a year, it appears that Pfizer has sufficient supplies of lot# 4030024 to address all Coral Snake envenomations until April 2014. However, that does not mean your local Hospital has requested and stocks this antivenom. If your hospital needs a copy of this FDA letter with instructions on how to secure Wyeth Coral Snake antivenom lot #4030024, go to:www.FDA.gov; click on Biologics Blood Vaccine tab and type in Coral Snake antivenom in the search box. So what happens on May 1, 2014? Will another extension be issued? I don’t think so.
In 2010, Biotoxins/Reptile World Serpentarium in Saint Cloud, Florida, was selected to supply Pfizer Pharmaceutical with Eastern Coral Snake (Micrurus fulvius) venom from a variety of counties in Florida. Two other venom labs, Medtoxin Venom Laboratories/Reptile Discovery Center (Deland) and Agritoxins Labs (Saint Cloud), are collaborating on the project. Coral Snakes, unlike the other venomous snakes in Florida, are not easy to come by. Even the best licensed collectors do not run across them often. So the dilemma of getting enough Coral Snakes to meet pharmaceutical needs had to be addressed. Emails and word of mouth soon spread and the traveling began. Calls started to come in 24/7. We have responded to nearly every call from Tallahassee to Jacksonville and all the way south to Homestead. To date, 60,000 miles have yielded close to 250 Coral Snakes colonized in these three separate locations. This strategy ensures that any potential epidemic illness would be contained in one colony at one facility. All specimens are tube-fed a specially formulated diet that allows excellent weight gain and growth. Some periods of demand for venom required collection on a 5 day rotation, which is twice more often than venom is normally collected. This occasional 5 day schedule of venom extraction did not impact the snakes in any negative way. As demand decreased, the 10 to 12 day venom collection schedules were resumed. Contrary to many beliefs, Coral Snakes do very well under these circumstances gaining weight and strength. Many specimens were received with animal bite lacerations, weed eater injuries and a whole host of other fresh wounds, as you might imagine, coming out of people’s garages, under patio stones, on golf courses, in swimming pool skimmers, in houses and on one occasion in a gas grill. The injured specimens with wounds were treated and healed quite well on the venom line.
The project utilized Coral Snakes weighing from 8 to 175 grams. Total body length ranged from 9 to 43 inches. Specimens as small as 8 grams, were raised to adults during the project. The committed efforts of Floridians made it possible to produce an adequate supply of Coral Snake venom to be utilized in the manufacturing of new FDA approved antivenom. Referrals from the Florida Fish and Wildlife Conservation Commission, Zoos, The Venom One organization, Bush Wildlife Sanctuary, Florida State University Biology Department, licensed venomous keepers and individual residents made this possible. To this we applaud all of you for contacting our venom labs when you encountered a Coral Snake. Ok, let’s continue this story---.
Can we assume that because all previous extensions of antivenom were from October to October that possibly we will see new antivenom available in May of 2014? Will it be a whole IgG antivenom (like the Original Wyeth)? Will horses be the host animal for production? How many vials will be required for a bite? How much will each vial cost?
Pfizer has not made public any information to date. I have some thoughts on these questions that I will share. I feel like we are very close to hearing about a new product that will put us back on track to treating every "positive" Coral Snake envenomation with an FDA approved antivenom, sometime in the first half of 2014.
When treating Coral Snake envenomations, waiting for symptoms to develop before treatment can, on some occasions, lead to significant complications. This practice is necessary in an antivenom shortage and is common protocol today at many hospitals. With adequate antivenom supplies, this will no longer be necessary during initial treatment. I think the new Pfizer antivenom will be a duplicate of the original Wyeth antivenom, not one of the newer FAB protocols. The newer FAB (Fragmented AntiBody-smaller mass) type protocols would require years of clinical trials at selective sites delaying the delivery and increasing cost. Whole IgG (larger antibody) antivenoms, like the old Wyeth, remain in the body longer doing their job of neutralizing venom components; therefore, fewer vials of whole IgG antivenom are generally needed. The smaller (FAB) type antivenoms are eliminated by the body quicker, generally requiring more vials of antivenom on a continuous basis. I would suspect the old protocol of giving 5 vials to start would be effective and in most cases adequate with Pfizer’s new antivenom. Antivenom production can be accomplished using four to six horses. The horses do well and are not harmed during the blood donation process. They receive exceptional care and live a normal life.
Coral Snake envenomations are so few they fall in the "orphan disease" category (a disease that affects a small percentage of the population). Initiatives to provide alternate antivenom availability will certainly play a role in treatment going forward. The one question I will not guess at is the retail price on a vial of the new antivenom. Let’s hope the pricing does not preclude adequate dosing.
Our 3 venom labs will continue to produce venom for Pfizer on a regular basis as long as antivenom is being produced. What I have shared with you in this article is my own opinion. Stay tuned for the rest of the story, as this most interesting situation continues to unfold.