April 29, 2019
Trial finds patients receiving CroFab® antivenom less likely to use opioids for pain control

Philadelphia, PA, 29 April 2019

BTG plc (LSE: BTG), the global healthcare company, today announced the publication of a trial, "Antivenom Treatment is Associated with Fewer Patients Using Opioids after Copperhead Envenomation" in the Western Journal of Emergency Medicine (WestJEM).
 
“In a randomized, double-blind, placebo-controlled, clinical trial of CroFab® for treatment of copperhead snakebite, patients that received CroFab® were less likely to use opioids for pain control during recovery,” said Dr. Charles Gerardo, Chief of Emergency Medicine at Duke University and expert in copperhead snake envenomation. “This is completely consistent with antivenom’s effect on tissue injury and improved recovery. No patients reported use of opioids once they had regained full function. As the CroFab® patients recovered more quickly, they required a shorter duration of opioids.”
 
The secondary analysis was performed using data from a randomized clinical trial designed to determine the effect of CroFab® on limb injury recovery following mild to moderate copperhead envenomation. The original trial results were published in the Annals of Emergency Medicine in 2017 as “The Efficacy of Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Versus Placebo Plus Optional Rescue Therapy on Recovery from Copperhead snake Envenomation: A Randomized Double-Blind, Placebo-Controlled, Clinical Trial.”
 
“Exposure to opioids as a result of an initial prescription from the emergency department may contribute to long term opioid abuse and addiction,” said Dr. Caroline Freiermuth, Associate Professor of Emergency Medicine at the University of Cincinnati. “Patients who continue to use opioids for more than five days following an initial opioid prescription have a higher risk of ongoing opioid use at a year than those patients who have stopped. When assessing the efficacy of treatments for painful diseases such as snakebite, we should more consistently assess the treatment’s impact on opioid use as was done in this study.”
 
Seventy-four patients were enrolled in the parent trial. Forty-five received CroFab®. Twenty-nine received a placebo. A smaller proportion of patients treated with CroFab® reported opioid use, nearly 41 percent versus nearly 61 percent of those in the placebo group. The proportion of patients using opioids remained smaller in the CroFab® group at every follow-up time point.
 
The resulting model estimated the odds of using opioids after hospital discharge among those who received placebo was nearly 6 times that of those who received CroFab®.
 
A secondary analysis, “Early Administration of Fab Antivenom Resulted in Faster Limb Recovery in Copperhead Snake Envenomation Patients,” showing early treatment with CroFab® led to faster limb recovery was published in Clinical Toxicology in 2018. Another secondary analysis, “The Validity, Reliability and Minimal Clinically Important Difference of the Patient Specific Functional Scale in Snake Envenomation,” was published in PLOS One this year.
 
Real world safety data has also been published in two studies, “Acute Adverse Events Associated with the Administration of Crotalidae Polyvalent Immune Fab Antivenom within the North American Snakebite Registry,” and “Incidence of Allergic Reactions to Crotalidae Polyvalent Immune Fab,” in Clinical Toxicology in 2018. These studies demonstrated a low rate of adverse reactions (between 1.4 – 2.7%) in patients treated with CroFab.
 
Between 5,000 and 9,000 people in the U.S. seek treatment in an emergency department due to a snakebite each year. There were 2,048 calls to U.S. poison centers in 2016 for copperhead bites. There were close to another 2,000 calls in which the type of snake was not identified.

About CroFab®
CroFab® is the only FDA-approved treatment for all North American pit viper envenomations in adult and pediatric patients.  Since 2001, CroFab has been used to treat more than 50,000 patients. It is developed through a unique manufacturing process for exceptional quality and purity. It is derived from Australian sheep, is free of prions and viruses, and produced exclusively from U.S. snakes. CroFab® has been proven to halt local effects including edema, ecchymosis, and treat the source of pain. It has been found to resolve systemic effects such as nausea, vomiting, dizziness and tachycardia. CroFab® has also been found to reduce coagulation abnormalities, such as thrombocytopenia, hyperfibrinogenemia and spontaneous bleeding.
INDICATION

CroFab® is indicated for the management of adults and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads, and cottonmouths/water moccasins.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Do not administer CroFab® to patients with a known history of hypersensitivity to any of its components, or to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.

WARNINGS AND PRECAUTIONS
Coagulopathy: In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time, occurred in approximately half of the patients studied; one patient required re-hospitalization and additional antivenin administration. Recurrent coagulopathy may persist for 1 to 2 weeks or more. Patients who experience coagulopathy due to snakebite should be monitored for recurrent coagulopathy for up to 1 week or longer. During this period, the physician should carefully assess the need for re-treatment with CroFab® and use of any type of anticoagulant or anti-platelet drug.

Hypersensitivity Reactions: Severe hypersensitivity reactions may occur with CroFab®. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to CroFab®. Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia).

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus and back pain. Adverse reactions involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 12 of the 42 patients. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment and one patient discontinued CroFab® due to an allergic reaction. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur.
To report suspected adverse reactions, contact 1-877-377-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for CroFab.

About BTG Pharmaceuticals.
BTG Pharmaceuticals provides antidotes that counteract the potentially life-threatening effects associated with exposure or overexposure to certain toxins. These acute care products are typically used in emergency rooms and intensive care units to treat patients for whom there are limited or no existing treatment options. We are dedicated to delivering quality medicines that make a real difference to patients through the development, manufacture, and commercialisation of pharmaceutical products. To learn more about BTG Pharmaceuticals, please visit: btgplc.com/pharmaceuticals
 
For further information contact:

BTG                           
Chris Sampson, Corporate Communications Director
+44 (0)20 7575 1595; Mobile: +44 (0)7773 251 178

Greentarget
Chris Gale, Vice President
+1-646-695-2883; Mobile: +1-203-570-4681