In an act lauded as an unusual expression of regulatory and corporate heart, the drug Colcrys is being made available at a discount to income-eligible owners of Chinese Shar-Pei dogs suffering from an illness peculiar to their breed.
The disease, called Familial Shar-Pei Fever (FSF), is characterized by periodic unexplained bouts of high fever and swelling of the joints. The chronic inflammation can lead to kidney failure and early death. FSF is similar to Familial Mediterranean Fever (FMF), a rare genetic disease in humans. The severity and frequency of inflammation attacks in both illnesses may be reduced by colchicine, the active ingredient in the brand-name drug Colcrys. More commonly in humans, colchicine is used for gout.
The arrangement by Colcrys maker URL Pharma to extend its "patient assistance program" to shar-pei owners is unprecedented because Colcrys is not approved for veterinary patients. Ordinarily, drugs may not be promoted by their makers for off-label use, although the prescribing of medications for other than their approved applications is common and legal in medical practice.
In this instance, following a sharp price increase — from 9 cents to $5 per pill, according to a commentary in the New England Journal of Medicine — more than 1,000 shar-pei fanciers petitioned the company and the FDA to consider their breed’s plight. FSF is believed to affect one out of four shar-pei in the United States.
Last week, petitioners learned that their effort had paid off.
In a letter posted March 31 on sharpeiforums.com, Dr. Richard Roberts, president and CEO of URL Pharma, wrote:
"We were completely unaware of the needs of shar-pei dogs and the serious impact of Familial Shar-Pei Fever (FSF) until we received your e-mails. In particular, several e-mails ... provided a reasoned, highly informative presentation to Customer Service that educated us on the issue and asked for our help. When the situation of shar-pei owners and their pets was brought to my attention, we engaged legal counsel on this issue to contact FDA seeking permission to help shar-pei owners. There are many laws and regulations surrounding this issue which required us to get assurance from FDA that nothing untoward would happen to us for our helping you."
A spokeswoman for the FDA Center for Veterinary Medicine (CVM) confirmed that the agency had, in effect, given its blessing to URL Pharma’s proposal, although she noted that the FDA did not give permission per se.
"CVM does not object to URL Pharma enrolling shar-pei owners in its existing Patient Assistance Program for the purpose of providing Colcrys to qualifying dog owners. CVM reminds URL Pharma that they may not in any way promote Colcrys to treat any extralabel use," Laura Alvey, deputy director of communications for CVM, said in an e-mail response to questions.
In other words, while the company may assist shar-pei owners, it cannot solicit their use of Colcrys.
Under the patient assistance program, as described by Roberts, shar-pei owners with annual household incomes up to three times the federal poverty level ($67,050 for a family of four, for example), may obtain Colcrys for free.
Those with annual household incomes up to four times the federal poverty level ($89,400 for a family of four) may obtain the drug for $5 a month.
Those with annual household incomes up to six times the federal poverty level ($134,100 per year for a family of four) may obtain the drug for $25 a month.
Dog owners may apply by calling (888) 811-8423 weekdays between 8 a.m. and 6 p.m. Eastern.
Dr. Linda Tintle, co-owner of Wurtsboro Veterinary Clinic in New York, an expert in shar-pei health and a long-time researcher in FSF who pioneered the use of colchicine to control the disease, said the actions of the drug company and regulatory agency were unexpected. "I’m kind of shocked," she said. "I have never seen anything like it."
The Rev. Jan Wortham-Morgan, a moderator on sharpeiforum.com who initiated an online petition drive and e-mail-writing campaign, was equally surprised. "I don’t think the public realizes how rare it is that something like this works," she said.
The FDA and URL Pharma each complimented the other for its part. "FDA appreciates their willingness to allow shar-pei owners to participate..." Alvey said. "We don’t track these things so I can’t say for certain but to the best of our knowledge we’re not aware of another company doing this before."
URL Pharma chief Roberts noted: "FDA ‘went out on a limb’ for shar-pei owners in this case (we have, too). I have never seen FDA do this before in my 23 years in the pharmaceutical industry."
The act engendered goodwill on an otherwise sore subject. The price of colchicine skyrocketed because the FDA granted URL Pharma an exclusive license for the medication. The company won the license after performing studies in 2007 to demonstrate the drug’s safety and efficacy. Up to that point, colchicine, an herbal medicine derived from the autumn crocus and used in some form by humans for millennia, was accepted as a legal drug under a grandfather clause in the 1938 Food, Drug and Cosmetic Act that required new drugs to be reviewed for safety.
Dr. Jeffrey Vidt, a veterinarian and vice president of the Chinese Shar-Pei Club of America, called the situation "a demonstration of capitalism at its worst." On his website in December, Vidt urged shar-pei owners to contact the FDA and URL Pharma in a coordinated effort to let their concerns be known.
Wortham-Morgan said the campaign was greatly aided by the timely publication of a study in the March 2011 edition of PLoS Genetics that for the first time described the pathogenesis of FSF and suggested why colchicine would have a therapeutic effect. The researchers found that, like FMF and gout, Familial Shar-Pei Fever involves dysregulation of the inflammasome, a complex of proteins in the innate immune system that cue the inflammatory response.
The study was co-written by Tintle and three researchers from Uppsala University in Sweden: Mia Olsson, Kerstin Lindblad-Toh (also of the Broad Institute of Harvard University and the Massachusetts Institute of Technology) and Jennifer R.S. Meadows, and included the work of 20 other collaborators.
Among their findings, the researchers discovered that the gene that predisposes the breed to periodic fever syndrome is the same gene responsible for the thick, wrinkled skin that defines shar-pei dogs in the West. (A photograph in their paper of the traditional shar-pei type still common in China shows a dog with markedly fewer wrinkles and a trimmer muzzle. Western-bred shar-pei are referred to as "meatmouth" type.)
Wortham-Morgan believes the blockbuster findings influenced the FDA and URL Pharma’s reviews. "I think the timing of (the) publication and its scientific impact was a huge factor," she said.
Alvey at the FDA did not answer a question about the determining factors in the agency’s decision, and a representative for URL Pharma did not respond to a request for an interview with Roberts.
Whatever the background, Carrie Battel is grateful for the outcome. Battel, of Buffalo, N.Y., bought a pug/shar-pei mix, known as Ori-Pei, from a breeder in Missouri in October. From the start, Battel noticed that the pup, then 5 months old, seemed lethargic.
Worried, Battel took the pup she named China with her to work at the assisted-living center where she is a nurse. China worsened, shaking and spiking a fever. Battel rushed her to an emergency veterinary hospital, which prescribed antibiotics. The pup seemed to improve. But "two weeks later, we went through this again," Battel recounted. "A month later, it happened again."
Eventually, on the recommendation of her aunt, Battel brought China to Dr. Teresa Labuszewski. Labuszewski had never before seen a case of Familial Shar-Pei Fever. Battel, who had been researching the issue, asked if they could try colchicine.
Labuszewski read up on the condition and the medication and learned the drug could be toxic at high doses. But the pup was running temperatures of 106 and 107 degrees, well above the 102.5 degrees that is considered the high end of normal in dogs.
"I was a little scared (of colchicine) but I figured, what’s the alternative?" Labuszewski said.
At the time, colchicine still was available in generic form. Battel could buy a month’s supply for $12. And the medication, aside from causing diarrhea during the first week, made China well. She became "a normal, happy dog," Battel said.
Then last month, Battel discovered that the drug no longer was available as a generic, and the brand-name version would cost her close to $200 a month. As a single woman earning $42,000 a year, Battel said the price wasn’t something she could easily absorb. And yet she felt that she must. When she ran out of medication while searching for a pharmacy with a better price, within three days, China began snuffling as if she could barely breathe.
"It got to the point where she was sick and I said, ‘I don’t care. I’ll pay it. Anything for the dog,’ " Battel said.
Meanwhile, Labuszewski posted a message on the Veterinary Information Network, an online professional resource, asking colleagues if they knew of any alternatives.
The following day, Tintle responded with the news that URL Pharma had just announced it would include dogs with FSF in its patient assistance program. Battel plans to apply.