Colchicine a Case Study for What's Wrong With US Drug Pricing

Public spending on colchicine has grown exponentially over the past decade despite generics suggesting an uphill slog for patients seeking access to long-term therapy for gout or cardiac conditions.

Medicaid spending on single-ingredient colchicine jumped 2833%, from $1.1 million in 2008 to $32.2 million in 2017, new findings show. Medicaid expansion likely played a role in the increase, but 58% was due to price hikes alone.

The centuries-old drug sold for pennies in the United States before increasing 50-fold to about $5 per pill in 2009 after the first FDA-approved colchicine product, Colcrys, was granted 3 years' market exclusivity for the treatment of acute gout based on a 1-week trial.

If prices had remained at pre-Colcrys levels, Medicaid spending in 2017 would have totaled just $2.1 million rather than $32.2 million according to the analysis, published online November 30 in JAMA Internal Medicine.

The study was motivated by difficulties gout patients have in accessing colchicine, but also last year's COLCOT trial, which reported fewer ischemic cardiovascular events in patients receiving colchicine after myocardial infarction (MI), observed Natalie McCormick, PhD, Massachusetts General Hospital and Harvard Medical School, Boston.

"They were suggesting it could be a cost-effective way for secondary prevention and it is fairly inexpensive in most countries, but not the US," she told theheart.org | Medscape Cardiology. "So there's really a potential to increase public spending if more and more patients are then taking colchicine for prevention of cardiovascular events and the prices don't change."

The current pandemic could potentially further increase demand. Results initially slated for September are expected this month from the COLCORONA trial, which is testing whether the anti-inflammatory agent can prevent hospitalizations, lung complications, and death when given early in the course of COVID-19.

University of Oxford researchers also announced last week that colchicine is being added to the massive RECOVERY trial, which is studying treatments for hospitalized COVID-19 patients.

Notably, the Canadian-based COLCOT trial did not use Colcrys, but rather a colchicine product that costs just 26 cents a pill in Canada, roughly the price of most generics available worldwide.

Authorized generics typically drive down drug prices when competing with independent generics, but this competition is missing in the United States, where Colcrys holds patents until 2029, McCormick and colleagues note. More than a half dozen independent generics have FDA approval to date, but only authorized generics with price points set by the brand-name companies are available to treat acute gout, pericarditis, and potentially millions with MI.

"One of the key takeaways is this difference between the brand names and the authorized generics and the independents," she said. "The authorized [generics] have really not saved money. The list prices were just slightly lower and patients can also have more difficulty in getting those covered."

For this analysis, the investigators used Medicaid and Medicare data to examine prices for all available forms of colchicine from 2008 through 2017, including unregulated/unapproved colchicine (2008–2010), generic combination probenecid–colchicine (2008–2017), Colcrys (2009–2017), brand-name single-ingredient colchicine Mitigare (approved in late 2014 but not marketed until 2015), and their authorized generics (2015–2017). Medicare trends from 2012 to 2017 were analyzed separately because pre-Colcrys Medicare data were not available.

Based on the results, combined spending on Medicare and Medicaid claims for single-ingredient colchicine exceeded $340 million in 2017.

Inflation- and rebate-adjusted Medicaid unit prices rose from $0.24 a pill in 2008, when unapproved formulations were still available, to $4.20 a pill in 2011 (Colcrys only), and peaked at $4.66 a pill in 2015 (Colcrys plus authorized generics).

Prescribing of lower-priced probenecid–colchicine ($0.66/pill in 2017) remained stable throughout. Medicaid rebate-adjusted prices in 2017 were $3.99/pill for all single-ingredient colchicine products, $5.13/pill for Colcrys, $4.49/pill for Mitigare, and $3.88/pill for authorized generics.

Medicare rebate-adjusted 2017 per pill prices were $5.81 for all single-ingredient colchicine products, $6.78 for Colcrys, $5.68 for Mitigare, $5.16 for authorized generics, and $0.70 for probenecid–colchicine.

"Authorized generics have still driven high spending," McCormick said. "We really need to encourage more competition in order to improve access."

In an accompanying commentary, B. Joseph Guglielmo, PharmD, University of California, San Francisco, pointed out that the estimated median research and development cost to bring a drug to market is between $985 and $1335 million, which inevitably translates into a high selling price for the drug. Such investment and its resultant cost, however, should be associated with potential worth to society.

"Only a fraction of an investment was required for Colcrys, a product that has provided no increased value and an unnecessary, long-term cost burden to the health care system," he writes. "The current study findings illustrate that we can never allow such an egregious case to take place again."

McCormick reported grants from Canadian Institutes of Health Research during the conduct of the study. Guglielmo reported having no relevant conflicts of interest.

JAMA Intern Med. Published online November 30, 2020. Abstract, Commentary

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