Welcome to our new website! If this is the first time you are logging in on the new site, you will need to reset your password. Please contact us at email@example.com if you need assistance.
Your membership opens the door to free learning resources on demand. Check out the Member Knowledge Center for free webcasts, publications and online courses.
Hear from leaders around the globe as they share insights about their experiences and lessons learned throughout their certification journey.
Posted 12 February 2013
The so-called Animal Rule pathway, a regulatory mechanism meant to allow companies to skirt the ethical issues inherent in testing products intended to treat or prevent the effects of dangerous pathogens, could soon have another rare approval if early reports from US regulators are any indication of its safety and effectiveness.
That product, Cangene's Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G) - (Equine), is a sterile solution of purified antibody fragments intended to counter the effects of exposure to botulism, a paralyzing illness caused by toxins produced by Clostridium botulinum and related species.
Cangene's briefing on the product, submitted in advance of FDA's Blood Products Advisory Committee meeting on the drug, notes that the toxins products by C. botulinum, of which there are seven, are "among the most potent neurotoxins known to science."
But while there are some botulism antitoxins already approved by FDA, Cangene says its product fills a distinct need. "Currently, no specific, licensed therapies are available to treat all seven known serotypes," it wrote. "Given the inability to rapidly detect and identify botulinum neurotoxin (BoNT) serotypes in emergency situations, there is a critical need for a single effective treatment against all BoNT serotypes."
But as with other dangerous pathogens, such as anthrax and the plague, testing the safety and efficacy of products intended to treat C. botulinum is a challenge. Unlike more normal products, such as those intended to treat heart disease, you can't exactly go out and round up patients exposed to the plague-there aren't any (or at least you hope there aren't). Instead, sponsors are supposed to rely heavily on animal models under the so-called Animal Rule, sometimes referred to as the animal efficacy rule.
Under that pathway, animals-rats, mice, guinea pigs, monkeys, pigs, etc-are exposed to the pathogen in question, while only humans are exposed to the treatment to make sure it's safe for human consumption.
FDA has recently cleared two products, Johnson and Johnson's plague antibiotic, Levaquin (levofloxacin), and GlaxoSmithKline's anthrax-treating monoclonal antibody, raxibacumab, under the pathway, both in 2012. Four additional products, Cyanokit for cyanide exposure, pyridostigmine bromide for Soman pre-exposure prophylaxis, doxycycline for plague and ciprofloxacin for anthrax, were approved prior to 2012. Only raxibacumab was a novel molecular entity unknown to FDA.
And soon, Cangene's botulism antitoxin could make number seven. FDA's assessment of the data showed numerous indications of efficacy. In a test of all seven C. botulinum serotypes on guinea pigs, all 238 animals survived testing when using Cangene's product. Just 31 animals on the placebo treatment survived, 17 of which were exposed to serotype G.
That isn't to say the data showed flawless efficacy. Just 14 of 30 rhesus macaques survived exposure to Serotype A, though none of the placebo group of 30 animals did. Those animals that did not survive in the treatment group survived more than twice as long as their control group counterparts-a potential benefit for physicians hoping to carry out additional testing and treatment.
On the human safety side, common side effects included headache, somnolence, fever, rash, lymphadenopathy, tonsillar hypertrophy, nausea, extremity pain and upper respiratory tract infections. Six deaths occurred during the course of the trial, though Cangene determined that none were related. FDA said it requested additional information on three of those deaths, saying at least one appeared to be consistent with serum sickness and the other two seemed potentially related as well.
Now, the question of approval is before the Blood Products Advisory Committee, whose recommendation could influence FDA as it makes its own decision, likely about a month thereafter.
That committee is meeting on 12 February 2013. More information can be found here.
Tags: Animal Rule
Regulatory Focus newsletters
All the biggest regulatory news and happenings.