Merck Serono's Cyanokit approved in Europe

Dec 3 2007

Merck Serono, a division of Merck KGaA, announced today that the European Commission has granted marketing authorization for its product Cyanokit (active substance: hydroxocobalamin) for the treatment of known or suspected cyanide poisoning in both adults and the pediatric population.

Cyanokit(R) is the first cyanide antidote that is approved via the European Centralized Procedure. Cyanokit(R) is the only cyanide antidote approved in the European Union, the United States of America and Japan.

The unique mechanism of action of Cyanokit(R) is based on its ability to tightly bind cyanide ions. It may be used in a hospital setting or on-site at an emergency situation. Cyanokit(R) is to be administered in conjunction with appropriate decontamination and supportive measures. Cyanide poisoning is primarily caused by smoke inhalation during closed-space structural fires. Additional causes may include accidental or intentional ingestion, inhalation, dermal exposure during industrial accidents or a terrorist attack involving cyanide.

"The European approval of Cyanokit(R) is a key milestone for emergency health care professionals," said Roberto Gradnik, Head of Merck Serono's Operations for Europe. "They will now have a safe and effective product to treat people immediately for cyanide poisoning, either at the scene of a fire, accident or other emergency, or at the hospital. We expect the availability of Cyanokit(R) throughout Europe will have an impact on the survival and prevention of irreversible neurological injury of those who are poisoned by cyanide."

The European marketing authorization of Cyanokit(R) is supported by safety data in healthy adults and efficacy data in adults and pediatrics, including data from three studies carried out in subjects who had been exposed to smoke inhalation from fires. Due to ethical considerations, no controlled human efficacy studies have been performed.

Four uncontrolled clinical studies were conducted in known or suspected cyanide-poisoning victims. A total of 245 patients were included in these studies evaluating the efficacy of Cyanokit(R) as an antidote. Of the 213 patients in whom the outcome was known, the survival was 58%. Of the 89 patients who died, 63 were initially found in cardiac arrest, suggesting that many of these patients had almost certainly suffered irreparable brain injury prior to administration of Cyanokit(R). Among the 144 patients not in initial cardiac arrest whose outcomes were known, 118 (82%) survived. Furthermore, in 34 patients with known cyanide concentrations above the lethal threshold ( greater than or equal to 100 micro mol/l), 21 (62%) survived following treatment with Cyanokit(R). Where neurological assessment over time was possible, (96 of the 171 patients who presented with neurological symptoms prior to Cyanokit(R) administration), 51(53%) patients receiving Cyanokit(R) showed improvement or a complete restoration.

The most common side effects associated with Cyanokit(R) are red coloration of the skin, mucous membranes and urine, all of which are reversible.

"Clinical data show that Cyanokit(R) is very effective in treating cyanide poisoning, even in patients with extremely toxic levels of cyanide in their bodies, as well as in complex clinical settings including smoke inhalation in which the presence of cyanide is always presumptive," said Frédéric Baud, MD, Professor of Critical Care Medicine at Lariboisière hospital, Paris University VII.

"The favorable safety profile of Cyanokit(R) is very important in an emergency situation requiring rapid, life-saving treatment," added Dr Jean-Luc Fortin, MD, former Chief Medical Officer at the Paris fire brigade.

Cyanokit(R) received approval from the US Food and Drug Administration in December 2006 and from the Japanese Health Authority in September 2007.

The active ingredient in Cyanokit(R), hydroxocobalamin, is a precursor of vitamin B12. Hydroxocobalamin works by binding directly to the cyanide ions, creating cyanocobalamin, a natural form of vitamin B12, which is excreted in the urine.

Advantages of this approach are that methemoglobin is not produced and the oxygen-carrying capacity of the victim's blood is not lowered. Therefore, Cyanokit(R) is suitable for use in smoke inhalation victims. The most common adverse reactions seen in clinical trials of hydroxocobalamin with human subjects are transient and include: reddish discoloration of the skin, mucous membranes and urine, rash, increased blood pressure, nausea, vomiting, diarrhea, headache, decreased white blood cell count and injection site reactions. Allergic reactions have been observed. Usage may interfere with some clinical laboratory evaluations.

The initial dose of Cyanokit(R) for adults is 5 g, administered by intravenous infusion. Depending upon the severity of the poisoning and the clinical response, a second dose of 5 g may be administered up to a total dose of 10 g.