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 (hhs.gov).
seems very odd for insurers to refuse to pay for much cheaper off label 0.6 mg. I think you have found something interesting, important, and not just pharmaceutical company greed.
First there was the gout issue where the FDA took something widely available and used and made it more costly. Why ? Clinical Trials are not good in and of themselves, they are a means to an end. Millennia of non experimental experience was, I think, sufficient to prove safety and efficacy.
Now there is the hugely important exciting cardiovascular result. The clinical trial was totally worth the cost.
But maybe not the added deadweight loss of patent protection and a restricted label.
I think one solution is public funding of trials of currently cheap generic agents.
Another is the FDA getting over the obsession with clinical trials. 0.6 mg can’t be safe for gout but not heart disease. It seems very hard to believe 0.5 mg is effective and 0.6 isn’t. I think it is clear what should be done, by the FDA if necessary.
I need to think.
also fascinating and very important post.
Consider the impact of ACA medical loss requirements. The pool of money that insurers have to run their policies including profit is (1 – medical loss ratio) * premium revenue. The higher the overall claims volume, the more room they have for profit. The only good source of price discipline are the purchasers of policies. It’s kind of perverse that if an insurer figured out how to structure claimable treatments that would lower cost but give good health results they would be rewarded with lower profits. The leftover after medical loss is the insurers’ slice of pie, so work hard to get as big a pie as inattentive customers might not notice too much. Drive around and look at healthcare construction projects. The healthcare complex needs to have a healthy share of really sick folks or its finances are ruined and insurers are a key part of the complex.
i still dont see how depending patients (you know the folks that are prescribed for by MDs who have had a lot of education on what can or will work for us humans) seem to always be the ones who are supposed to figure out if its good for us and that we need it. but that seems to be the way health care in the US works (or doesnt). and ends up with patients have really bad out comes having a choice between not eating or not taking the drug and dying.
some take that as a sign
but its business health care, not helping patients is ok if it costs to much to do so
note it nor the FDA thats sets the price for the drugs. that a business decision
course why would they want to test at the new higher dose? maybe that higher does causes an impact the lower didnt? we expect our drugs o work and not hurt or kill us if prescribed correctly. picky us humans
Oh, also, I think the title should begin “One tenth of one Mg” not “One Mg”
Robert:
Correct. My mind gets ahead of my slowly typing fingers. I am not sure why you end up in the “trash.” I find others in there also when I dumpster dive. 🙂
Propecia and proscar have a similar relationship. They’re the same drug in different doses. The former is a quarter dose of the latter prescribed to prevent male pattern hair loss. The latter is prescribed for types of prostate cancer. The former sells for $4 a pill, the latter just pennies. If you want to see if you can keep your hair and your money, you can ask your doctor for a proscar prescription and buy a pill splitter.
Got a pill splitter because my meds are inbetweeners.
As the author claims, if the dosage is for one illness and he prescribes the other dosage, the drug store may not fill it and can legitimately deny doing so.