One Tenth of a Mg makes a big difference in a drug price and it has no clinical consequence

Interesting story about a pharma company taking an old drug finding a new usage for it at a particular dosage, filing a patent for the treatment at the specified dosage, and potentially blocking treatment of the disorder at a milligram higher dosage. Drug stores will not fill a prescription at a higher dosage if it is for the treatment of the disorder. Locked up both ways. And the cost to the patient went from pennies to ~$20/pill.

A Price Jump From Pennies to $20/Pill for the Same Drug, MedPage Today, Robert M Kaplan, PhD, and Michael H Weisman, MD

In June the U.S. FDA approved colchicine (Lodoco) as the first anti-inflammatory drug for the prevention of heart attacks and strokes among people with established heart disease or multiple risk factors. One recent review reported inflammation is a better predictor of future cardiovascular events and death than elevated cholesterol. The bright side of colchicine is its addressing of inflammation. The dark side to this approval is money or costs. Colchicine is being marketed as Lodoco in a particular dosage. Read on . . .

Not a new drug, Colchicine has been used for centuries. Indeed, there exist reports of it used to treat gout in ancient Greece over 2,000 years ago. It has remained a mainstay in gout treatment. For decades, it has also been used to treat familial Mediterranean fever and pericarditis. The authors point out its impact on heart issues. “A significant number of studies document colchicine reduces the risk of heart attacks and strokes among people with established heart disease.”

Another large 2019 study followed heart disease patients for ~2 years. The study tabulates how many people die from cardiovascular causes, were resuscitated, experienced cardiac arrest, had a heart attack or stroke, or needed urgent hospitalization. A comparison to those randomly assigned to take a placebo was made to those taking colchicine. The latter group taking colchicine were 23% less likely to experience one of these outcomes.

In 2006, the FDA created the “unapproved drugs initiative” for older generic drugs such as colchicine which had never been carefully evaluated by the FDA for safety and efficacy. Companies investing in these evaluations were rewarded with the opportunity to patent the molecules. Immediately the pharmaceutical companies began doing pharmacokinetic and clinical studies on older medications. Given the timing of the evaluations, the authors believe the primary goal of the companies is to bring low-cost generics, etc. to market as higher cost patented branded products.

In 2009, the FDA allowed URL Pharma to bring colchicine to market under the brand name Colcrys at a new dose of 0.6 mg per pill. Under the Orphan Drugs Act, URL Pharma was given 3 years of market exclusivity at this dose for the treatment of gout. URL Pharma also received an additional 7 years to exclusively market Colcrys for the treatment of familial Mediterranean fever at the same dose of 0.6 mg per pill. As part of these agreements, unapproved single-ingredient colchicine could not be sold in the U.S. It disappeared from the market.

The FDA and the public soon recognized that the unintended consequences of the initiative also included drug shortages and higher prices to treat gout. With these new approvals, the cost of colchicine went from pennies to about $5 per pill. The rheumatology community and other groups were extremely upset when their patients could no longer obtain fair priced generic colchicine.

During the decade following the price increase, there was a 27% reduction in the use of colchicine among gout patients who needed it. In 2013, applications were filed (and later granted in several countries abroad) for new patents allowing colchicine to be marketed as a novel agent for the prevention of cardiovascular events. While there are now 17 patents for Colcrys, until last June there was only one FDA approved form of colchicine.

Agepha Pharma now holds eight patents on Lodoco a 0.5 mg version of colchicine used for preventing heart disease or stroke. Now that the periods for exclusive marketing of Colcrys have expired, the price has come back down. Although the retail price remains around $5 per pill, large chain pharmacies sell it for less than $1/pill. Colcrys still remains FDA-approved for the treatment of gout at a dose of 0.6 mg per pill and generics remain unavailable.

Meanwhile, Agepha just released a retail price for Lodoco of $621 for a 30-day supply — nearly $21/pill. It will be available with a coupon at Walgreens for $170/month or about $5.66/pill. Using either the retail or coupon price, Lodoco can cost as much as four to six times more than Colcrys.

Colcrys and Lodoco are essentially the same drug. Both have only one active ingredient — colchicine. The only difference is a tiny variation in the dose. Colcrys has 0.6 mg of colchicine, while Lodoco has 0.5 mg — a difference that could be considered of no clinical consequence.

Doctors who want to use colchicine to prevent heart disease will be able to legally write off label prescriptions for the lower cost Colcrys. However, modern corporate medicine may deny payment because the dose of 0.6 mg was not approved for this indication (heart disease prevention). Insurers, regulators, or prescribers could theoretically argue that the higher dose was not tested for heart disease prevention and that 0.6 mg could be more toxic than 0.5 mg. Further, many physicians and healthcare provider groups avoid off label prescriptions because it may affect their quality ratings.

The authors are strong supporters of the search for safe and effective medications and recognizing the process requires significant investment. But colchicine has a long history of use and has established its value in several areas of medicine.

The unaffordability of prescription drugs remains an important driver of uncontrollable healthcare costs. For those with inadequate resources or lack of health insurance, allowing this well-established generic medication to become patented and hence unaffordable to some has the potential to produce significant harm. The authors and I hope Congress and the FDA will take this issue seriously.

Prescription Drug Price Increases for 2016 -2022, Angry Bear, ASPE (