FDA Review of Ancient Drug (Colchicine) Spikes Price

Wild saffron, aka autumn crocus (Colchicum autumnale), has been used for over 3,000 years to ease inflammation. An ancient Egyptian papyrus recorded its use for pain and swelling. A Greek physician used the plant to treat gout 2,000 years ago. In the early 19th century, a French chemist isolated the active ingredient which became known as colchicine.

Colchicine Gets Recognized By “Modern” Doctors

Colchicine has been used by physicians for hundreds of years to treat gout and calm inflammation. I learned about it in graduate school in the Department of Pharmacology at the University of Michigan over 50 years ago.

My “bible,” Goodman and Gilman’s The Pharmacological Basis of Therapeutics, stated:

“Colchicine is a unique anti-inflammatory agent in that it is largely effective only against gouty arthritis. It provides dramatic relief of acute attacks of gout and is an effective prophylactic agent against such attacks.”

“Benjamin Franklin, himself a sufferer from gout, is reputed to have introduced colchicum therapy in the United States.”

Colchicine for the Heart!

My textbook of pharmacology was wrong about one thing, though. Colchicine is not just effective against gouty arthritis. By the late 1980s, there was a recognition that this very old medication could be helpful against cutaneous vasculitis. This condition involves inflammation of the walls of blood vessels in the skin.

By the turn of the 20th century researchers were starting to use colchicine to treat pericarditis. This involves inflammation of the very thin tissue that surrounds the heart like a sac. And not long after that they discovered that the drug reduced the risk of heart attacks in patients taking it to prevent gout attacks.

Colchicine also helped keep cardiac stents from clogging. This ancient medication also reduced the risk of atrial fibrillation after surgery (American Journal of Medicine, May, 2015).

In recent years researchers have reported that colchicine could reduce the risk of heart attacks and strokes. So why don’t cardiologists prescribe it more often?

I suspect that it does not fit well with their theory of heart disease. Many heart doctors focus on LDL cholesterol and other lipids as their primary targets for treatment. Inflammation has been perceived as a far less important factor.

The review in the American Journal of Medicine from 2015 concludes:

“Colchicine is one of the oldest therapeutic substances known to mankind, yet the scope of its benefits has only recently been the subject of active study. Because of its wide range of activities among inflammatory cells, its systemic effect and its relatively mild side effect profile at recommended doses, colchicine has proved to be beneficial in some common and frustrating conditions, including cardiovascular disease. Ongoing research will further elucidate the mechanisms of action and therapeutic utility of this historic medicine.”

Colchicine and the Food and Drug Administration

I cannot say how long colchicine has been prescribed in the United States, but I would bet it has been used for more than a century. It entered the market before the Food, Drug and Cosmetic Act of 1938.

The officials at the FDA “grandfathered” the drug because it had been used for so long, even though it had not been officially “approved” for safety and effectiveness. It was inexpensive, selling for pennies per pill.

The FDA Demands Data:

In 2006 the FDA decided that old inexpensive generic drugs like colchicine had not actually been officially approved by the agency. It created an unapproved drugs initiative that allowed a pharmaceutical manufacturer exclusivity. A “Viewpoint” published in JAMA, Feb. 11, 2013 was titled “The Colchicine Debacle.”

The author wrote:

“The US Waxman-Hatch Act mandates that market exclusivity must be awarded to a newly approved drug, and, consequently, the company [URL Pharma] was awarded 3 years of market exclusivity. In response, the company subsequently filed suit with the intent of removing all other colchicine competitors from the market.

“In addition to filing suit to remove other colchicine competitors from the market, the manufacturer increased the price of colchicine from what used to be pennies to almost $5 per pill. The result of these actions resulted in a substantially increased cost for patients, third-party payers, and the overall health care system. This increased cost was not isolated to the treatment of acute gout. Colchicine has been used for decades in the treatment of familial Mediterranean fever, a relatively uncommon disease. Consequently, as a result of the Orphan Drug Act, the manufacturer also received 7 years’ market exclusivity for the use of Colcrys in the treatment of familial Mediterranean fever. The result of this action was that no generic colchicine could be produced for this extended period.”

Inflammation vs. Cholesterol In Heart Disease?

An easily overlooked research paper was recently published by two of America’s most renowned cardiologists, Paul Ridker of Harvard and Brigham and Women’s Hospital and Steve Nissen of the Cleveland Clinic and their colleagues (Lancet, April 15, 2023).

Here is the key finding:

“Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP [C-reactive protein] was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC [low-density lipoprotein cholesterol].”

In other words, inflammation, as measured by a CRP test, was more important that LDL cholesterol in predicting a heart attack or a stroke. That would likely come as a shock to most health professionals. We’re not diminishing the importance of lipids, especially Lp(a), but inflammation is also a very big deal. Statins not only lower LDL cholesterol, but they also have some anti-inflammatory activity.

Speaking of inflammation, that’s why colchicine is such an interesting medication. But the cost of the latest version of this very old drug is mind boggling.

A fascinating article in MEDPAGE TODAY (October 12, 2023) was titled “A Price Jump From Pennies to $20/Pill for the Same Drug.”

The authors, Robert Kaplan, PhD, and Michael Weisman, MD, offer the following insights:

“Agepha Pharma now holds eight patents on Lodoco (simply 0.5 mg of colchicine) 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…

That bears repeating! In June, the FDA granted Agepha Pharma rights to market this medication under the brand name Lodoco to reduce the risk for heart attacks and strokes. The price…$21 per pill.

The FDA Has Created a Medication That is Out of Reach for Many:

In its efforts to improve the evidence for this ancient treatment, the Food and Drug Administration may have put colchicine out of reach for many patients. It’s what we call the law of unintended consequences.

A doctor who wants to prescribe Lodoco to prevent heart attacks and strokes would have to convince a patient’s insurance company that the price is justified. We suspect that many insurance companies are happy with statins at a few dollars a month. Will they pay for colchicine? Only time will tell.

Want to read more about colchicine to protect the heart? Here is a link to another article we wrote a few years ago. Colchicine can interact with many medications, so doctors and pharmacists should warn people about dangerous combinations. Common side effects can include digestive upset and fatigue.

Please share your thoughts about the price increase for colchicine from pennies to big bucks in the comment section below.