The ACR Advocacy list serve was on fire in December 2009 as members discussed the recent price increase for colchicine. Patients and physicians alike were shocked to discover that Colcrys, a new brand name colchicine, skyrocketed in cost after receiving approval for acute gout and familial Mediterranean fever (FMF), increasing in price from approximately 10 cents a pill to approximately five dollars a pill. For a twice-daily dose, the monthly cost of colchicine increased from $6 to $300! How did this happen, and will our patients be able to manage the sharp price increase for this previously “generic,” technically unapproved, drug?
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In order to determine how to best respond to this issue, ACR staff researched the use of colchicine and related Food and Drug Administration (FDA) regulatory oversight.
Colchicine was first isolated in 1820 by two French chemists and was included in the first Pharmacopoeia of the United States. Moving ahead almost 120 years to 1938, the Federal Food, Drug, and Cosmetic Act required drugs to be approved by the FDA for safety. Beginning in 1962, Congress required that new drugs must be FDA approved for efficacy as well as safety. The agency also evaluated drugs that had been approved between 1938 and 1962. This did not affect colchicine because it was created prior to 1938. In 2006, the FDA announced a new drug-safety initiative to remove unapproved drugs from the market. The guidance for the initiative, “Marketed Unapproved Drugs—Compliance Policy Guide,” affected colchicine as a marketed unapproved drug that required regulatory approval.
URL Pharma was the first manufacturer to step forward and complete the necessary regulatory testing for FDA approval. During the application process, a significant observation determined for the first time that colchicine toxicity was potentially exacerbated by drugs that inhibit CYP3A4, an enzyme involved in the metabolism of colchicine, and p-gylcoprotein, a protein involved in its oral absorption. Drugs that inhibit CYP3A4 and p-glycoprotein include chlarithromycin, erythromycin, cyclosporine, verapamil, diltiazem, ketaoconcazole, and itraconazole. Many of 169 patients who died presumably due to colchicine toxicity reported to the FDA’s adverse event reporting system (AERS) were on one of these drugs. A placebo-controlled study of colchicine in 184 acute gout patients comparing 1.8 mg over one hour to 4.8 mg over six hours demonstrated similar efficacy in both colchicine treated cohorts with less gastrointestinal toxicity associated with the shorter exposure with reduced dosage. This placebo-controlled study was published in the April 2010 issue of Arthritis & Rheumatism (p. 1060).
Based on these results and a literature review of the use of colchicine to treat FMF, the FDA granted URL Pharma three-year exclusivity for marketing for the indication of acute gout and seven-year exclusivity for the indication of FMF. Approval for chronic gout/prophylaxis was not granted.
After URL Pharma was granted exclusivity, they filed a lawsuit in California seeking a preliminary injunction against other manufacturers of colchicine. The court denied the motion and granted a request to transfer the injunction to the District of New Jersey.
ACR Speaks to the FDA
To better understand the process resulting in the approval of Colcrys, I scheduled a conference call with Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research (CDER) in Silver Spring, Md. She, along with Robert Rappaport, MD, director of the CDER’s Division of Anesthesia, Analgesia, and Rheumatology Products, and several other members of their team, participated in the call to discuss our concerns (a summary of this call is available at www.rheumatology.org). The FDA explained its rationale in bringing “unapproved” drugs under FDA control, citing experience with bioavailability issues discovered with Synthroid when undergoing review. Although the merit of going through the review process was clear, I noted that the FDA’s new policy was associated with unintended consequences that could hamper patient access to the therapy.
The FDA shared our concerns over the dramatic price increase of colchicine and stated it had hoped more manufacturers would come forward and complete the approval process. They agreed to provide us with a list of other colchicine manufacturers so that the ACR could encourage these companies to go through the FDA regulatory process.
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ACR Relays Concerns to URL Pharma
The next step was to communicate the ACR’s concerns to URL Pharma. I have corresponded with Matthew Davis, MD, PhD, the company’s chief medical officer, communicating our concern that the steep price increase will prevent patient access to colchicine. Dr. Davis explained their initial patient assistance program, which URL Pharma has agreed to expand to the following:
- Patients with household incomes up to three times the poverty level (up to $66,000 per year for a family of four) will have access to Colcrys prescriptions for $5 per month;
- Patients with a household income between three and four times the poverty level (up to $88,000 per year for a family of four) will receive Colcrys for $10 per month;
- Patients with a household income between four and five times the poverty level (up to $110,000 per year for a family of four) will receive Colcrys for $20 per month; and
- Patients with a household income between five and six times the poverty level (up to $132,000 per year for a family of four) will receive Colcrys for $30 per month.
Additionally, Dr. Davis stated that this program would apply to all patients, including those with Medicare and Medicaid, which is unusual for pharmaceutical assistance programs. He also said that the program would not be time limited. Patients with acute gout would receive payment assistance for 30 pills per month; those with chronic gout or FMF will receive assistance for 60 or 120 pills per month, respectively, depending on their prescription.
Although we are disappointed that the cost of colchicine has increased, progress has been made to ensure access for our patients through the expanded patient assistance program. We will continue to work with the FDA to encourage other manufacturers to seek approval, which will hopefully result in price competition and lower drug cost.
Rheumatology healthcare professionals will continue to face major issues as healthcare reform evolves. I believe this experience is representative of the ACR’s responsiveness to member concerns. Please contact ACR staff as issues arise so that we can work together to ensure that our voice is heard and so that patients with chronic musculoskeletal disease can continue to receive the proper care that they deserve.
Dr. Cohen is president of the ACR. Contact him via e-mail at [email protected].