Cannabinoids, Dupuytren, and Orphan Drugs

I was recently asked if medical marijuana might be helpful for Dupuytren disease. The short answer is “No one knows.”. The longer answer is much more interesting.

The late effect of Dupuytren disease is Dupuytren contracture. The medical term for the findings in Dupuytren contracture is fibrosis. Sclerosis also means the same thing. If either of these terms is in the name of a disease, it means there’s a problem of scar tissue forming where it shouldn’t: pulmonary fibrosis, cystic fibrosis, scleroderma, arteriosclerosis, and so on. It also means that it’s a problem disease because we don’t yet have a medicine which can stop abnormal scarring without causing other problems. So, fibrosis research is a hot area for investigation. All options are on the table, including cannabinoids, which are in marijuana.

There is a growing body of published research on the effects of cannabinoids on fibrosis.
National Library of Medicine: Cannabinoids and Fibrosis

Cannabinoids are compounds found in hemp/marijuana plants. There are many kinds of cannabinoids and many ways that these affect human biology, including the biology of inflammation and fibrosis.

I reached out to several researchers in this field, and the general answer was that some cannabinoids show potential for Dupuytren disease treatment. A problem in cannabinoid research is that not only does each plant contain many different types of cannabinoids with very different effects, but the mix of these compounds varies unpredictably in retail products. Right now, the only way to guarantee purity is to use cannabinoids synthesized in the lab rather than extracted from plants.

I was referred to Corbus Pharmaceuticals (I have no relationship or financial conflict of interest with Corbus) who are testing ajulemic acid, a synthetic cannabinoid. Ajulemic acid looks like a promising antiinflammatory/antifibrotic. It’s unique in that it doesn’t cross the blood-brain barrier, so it can work in the body without getting into the brain and without getting people stoned. I talked with the folks at Corbus about the possible use of ajulemic acid for Dupuytren disease. They were encouraging but explained that their research is only on drug development for rare diseases such as cystic fibrosis and scleroderma. They’re not going to investigate ajulemic acid for Dupuytren disease. The reason is cost. The average overall cost to get FDA approval and bring a brand new drug to market is over a billion dollars according to this study from Tufts University. However, FDA requirements are different and much less costly for “orphan drug” development, so Corbus is only evaluating ajulemic acid for orphan drug status.

What’s an orphan drug? According to the FDA website an orphan drug is developed to treat a rare disease or condition, and (from the FDA website)

the term “rare disease or condition” means any disease or condition which
(A) affects less than 200,000 persons in the United States, or
(B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug. Determinations under the preceding sentence with respect to any drug shall be made on the basis of the facts and circumstances as of the date the request for designation of the drug under this subsection is made.

By this definition, cystic fibrosis is a rare disease, but Dupuytren disease isn’t an orphan disease. It’s common, which makes it much more costly to get FDA approval of a brand new drug for Dupuytren disease than it is to get FDA approval of the same drug for a rare disease like cystic fibrosis. That’s just the way things are – but there’s a workaround. Once a drug is FDA-approved, it can be used off-label for other conditions. This is commonly accepted practice. The prescribing physician makes the decision, not the FDA.

Side note. The FDA doesn’t approve drugs – it only approves the claims drug companies make in their drug marketing. In theory, the FDA could approve a drug which not only didn’t work at all but also had bad side effects – as long as that’s what the drug company claimed about the drug. That’s why direct-to-patient drug ads include a long list of scary-sounding drug side effects. It falls on the prescribing physician to decide whether or not to prescribe the drug. That’s why drug company ads all suggest that you “ask your doctor”.

So, there’s hope. There are many FDA-approved drugs and more in development which have the potential for Dupuytren disease use, even if not developed specifically for Dupuytren disease. Before these can be tested, we have to have a better way to gauge their effectiveness than a finger joint protractor. This is the driving force behind the International Dupuytren Data Bank: a Dupuytren blood test. If you haven’t signed up yet, now is the time. If you have, great: now go spread the word!

Charles Eaton MD
Dupuytren Research Group


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