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Clinical Trials

Drug Repurposing

A reader has sent along the question: “Have any repurposed drugs actually been approved for their new indication?” And initially, I thought, confidently but rather blankly, “Well, certainly, there’s. . . and. . .hmm”, but then the biggest example hit me: thalidomide. It was, infamously, a sedative and remedy for morning sickness in its original tragic incarnation, but came back into use first for leprosy and then for multiple myeloma. The discovery of its efficacy in leprosy, specifically erythema nodosum laprosum, was a complete and total accident, it should be noted – the story is told in the book Dark Remedy. A physician gave a suffering leprosy patient the only sedative in the hospital’s pharmacy that hadn’t been tried, and it had a dramatic and unexpected effect on their condition.
That’s an example of a total repurposing – a drug that had actually been approved and abandoned (and how) coming back to treat something else. At the other end of the spectrum, you have the normal sort of market expansion that many drugs undergo: kinase inhibitor Insolunib is approved for Cancer X, then later on for Cancer Y, then for Cancer Z. (As a side note, I would almost feel like working for free for a company that would actually propose “insolunib” as a generic name. My mortgage banker might not see things the same way, though). At any rate, that sort of thing doesn’t really count as repurposing, in my book – you’re using the same effect that the compound was developed for and finding closely related uses for it. When most people think of repurposing, they’re thinking about cases where the drug’s mechanism is the same, but turns out to be useful for something that no one realized, or those times where the drug has another mechanism that no one appreciated during its first approval.
Eflornithine, an ornithine decarboxylase inhibitor, is a good example – it was originally developed as a possible anticancer agent, but never came close to being submitted for approval. It turned out to be very effective for trypanosomiasis (sleeping sickness). Later, it was approved for slowing the growth of unwanted facial hair. This led, by the way, to an unfortunate and embarrassing period where the compound was available as a cream to improve appearance in several first-world countries, but not as a tablet to save lives in Africa. Aventis, as they were at the time, partnered with the WHO to produce the compound again and donated it to the agency and to Doctors Without Borders. (I should note that with a molecular weight of 182, that eflornithine just barely missed my no-larger-than-aspirin cutoff for the smallest drugs on the market).
Drugs that affect the immune system (cyclosporine, the interferons, anti-TNF antibodies etc.) are in their own category for repurposing, I’d say, They’ve had particularly broad therapeutic profiles, since that’s such a nexus for infectious disease, cancer, inflammation and wound healing, and (naturally) autoimmune diseases of all sorts. Orencia (abatacept) is an example of this. It’s approved for rheumatoid arthritis, but has been studied in several other conditions, and there’s a report that it’s extremely effective against a common kidney condition, focal segmental glomerulosclerosis. Drugs that affect the central or peripheral nervous system also have Swiss-army-knife aspects, since that’s another powerful fuse box in a living system. The number of indications that a beta-blocker like propanolol has seen is enough evidence on its own!
C&E News did a drug repurposing story a couple of years ago, and included a table of examples. Some others can be found in this Nature Reviews Drug Discovery paper from 2004. I’m not aware of any new repurposing/repositioning approvals since then, but there’s an awful lot of preclinical and clinical activity going on.

36 comments on “Drug Repurposing”

  1. Barry says:

    Sildenafil went into the clinic for angina, came out for ED. Likewise, Rogaine was a cardiovascular project, came out for alopecia

  2. Barry says:

    Some drugs change careers before ever clearing the FDA. Sildenafil went into the clinic for angina, came out for ED. Likewise, Rogaine was a cardiovascular project, came out for alopecia

  3. cirby says:

    The most successful “repurposing” has to be Sildenafil.
    AKA Viagra.
    Originally for hypertension and angina…

  4. Allan says:

    Minoxodil for hypertension and then hair growth? (Not particularly, encouraging, I’ll grant.)

  5. Bob says:

    I think Sanofi’s Rimonabant (Accomplia) was initially aimed at Smoking Cessation but then switched to weight loss, until being yanked for psychiatric problems.

  6. Dr Jimbo says:

    Aspirin was mentioned in passing but is a major example of this: initially used as an analgesic, repurposed as a hugely important antiplatelet (and it looks like cancer prevention may be a 3rd major effect for which it gets used therapeutically).
    Not sure if selling aspirin for cardiovascular purposes ever made serious money for anyone – is that what we have in mind when we think of a successful repurposing?

  7. Barry says:

    Some drugs change careers before ever clearing the FDA. Sildenafil went into the clinic for angina, came out for ED. Likewise, Rogaine was a cardiovascular project, came out for alopecia

  8. anonano says:

    For Sildenafil it is repurposing but it didn’t have a FDA indication before going for ED.
    While I think what some people see of repurposing is a drug on the market (or removed from it) with an indication get a new approval later for new indications, not known when it got the 1st approval.

  9. Wavefunction says:

    Not FDA approved, but isn’t AZT also an example? I believe it was originally a part of an anticancer screen.

  10. anonymous says:

    Again, not an approved indication, but Gemzar was originally designed/synthesized by Larry Hertel as and anti-viral but ultimately was registered and used as an anticancer agent.

  11. Anonymous says:

    Rituximab, primarily developed for hematologic malignancies, now does over $1B/yr. in approved autoimmune disorders (RA, GPA/MPA).

  12. John LaMattina says:

    I really don’t consider sildenafil (Viagra) a repurposed drug. It was put into the clinic as a PDE-5 inhibitor designed to elevate endogenous NO levels. The initial indication studied was, in fact, angina but elevating NO was thought to have potential across a variety of diseases where vasodilation was sought. Sildenafil proved to be a vasodilator in an organ not originally studied. It also works in the lung as is approved for primary pulmonary hypotension.

  13. Tricyclic antidepressants originally tested in clinic as antituberculosis agents, sense of euphoria being an unexpected reported side effect.

  14. CMCguy says:

    Not sure if this drug is captured in the C&ENews or NRDD articles or even if still being used today but an old WWII anti-malarial hydroxychloroquine was once used as an anti-inflammatory to treat lupus and a few other conditions.
    Didn’t the NIH initiate a program a couple years ago to examine alternate uses for approved and unapproved drugs (at least in lab models)? I think there are many in Pharma R&D and even Clinical MDs that are greatly attuned with curiosity and questions about subtle influences of giving a drug while I think once a drug is approved most people/MDs do focus only on the negative side affects on the labels, which definitely can’t ignore, therefore wonder how many potential positive response hints can be overlooked because observational and connectivity sensitivities are lacking?

  15. Pete says:

    Tecfidera – or methyl fumarate, repurposed from an industrial chemical to a therapy for MS
    I got this from this blog last year sometime
    $54000 a year, but you can buy 250 g for £50, which is enough for nearly 3 years supply at 240 mg a day

  16. simpl says:

    Thanks for the insight on ‘slippery’ autoimmune drugs. Fingolimod was in phase III transplant trials, then was reborn as an MS drug.
    Tropisetrone was designed as a selective serotonin drug. It didn’t work in migrane, instead as an anti-emetic. Sandoz had had decades of success in migraine products, but R&D work in migraine ceased soon after. The list of sub-types is now longer.

  17. psi*psi says:

    Leuprolide–first prostate cancer, then endometriosis and fibroids.

  18. Anonymous says:

    Methotrexate for cancer, RA, and ectopic pregnancy.

  19. Anonymous says:

    Solanezumab has been repurposed as bathroom tiling grout.

  20. Lyle Langley says:

    @#5, Bob…
    Rimonabant is/was not a repurposed drug. The smoking cessation and weight loss were running concurrently. If I remember from my time at Aventis/sanofi-aventis, the thought was it may get approved quicker for smoking cessation due to the larger clinical trials needed for weight loss.

  21. Anonymous says:

    Peroxynitrites have been repurposed as hypnotics. Yawn.

  22. PorkPieHat says:

    How about pregabalin (Lyrica):
    invented by Rick Silverman, developed first by Parke Davis as an anticonvulsant, but now widely used (repurposed) for fibromyalgia.

  23. KYosce says:

    Methylene Blue. Originally an anti-malarial. Repurposed to treat methemoglobinemia and for prevention of ifosfamide-induced encephalopathy Also as a practical joke 😉

  24. okemist says:

    Lomitapide was developed by BMS as a statin then dropped. Not a stretch repurpose but picked up by Aegerion and developed for hypercholesterolemia. Also Lavitra was first developed by Sterling for low intraocular blood pressure and they noted the side effects and dropped the compound. When Viagra came out Bayer dug the work out of the archives and bought it to market.

  25. Nick K says:

    A couple of years ago a non-nucleoside reverse transcriptase inhibitor was being developed for HIV (sorry, can’t remember its name or that of the company). It was found to elevate excretion of uric acid by a novel mechanism, and is now being developed as a treatment for gout.

  26. tangent says:

    Iproniazid as a MAOI antidepressant; I don’t remember if it was actually approved for TB in the first place or if it was in trials?
    (Erythromycin as a GI motility drug is off-label, I believe, but I just love that one.)

  27. Random academic says:

    Hey, I’ve got some great data with a bunch of rhodanines, polyphenols and and circumin analogs in an anti-cancer assay but on looking in the literature I see they also show activity in diabetes, Alzheimer’s and anti-viral assays. Surely the greatest repurposing story just waiting to unfold? These drugs are gonna be blockbusters when everyone wakes up to their potential!

  28. Enoch says:

    Weren’t Substance P antagonists supposed to be “can’t miss” treatments for depression? Aprepitant finally made it as an anti-emetic.

  29. Anon says:

    Rapamycin for cancer after approval as an immunosuppressive agent.

  30. Chris says:

    Wellbutrin the anti-depressant got re-verified so it could be renamed Zyban.

  31. SteveM says:

    Finasteride (Propecia) first BPH then hair loss.
    A more recent one is Guanfacine first for hypertension then ADHD.
    BTW, 30 1 mg tablets of generic Guanfacine go for 4 bucks. So 2 tabs per day is 8 bucks a month. While the branded Intuniv which is a 2 mg delayed release version is 300 bucks a month.
    How taking 1 one tab versus 2 twice a day is worth $292 a month, ($3504 a year) is beyond me.

  32. anona says:

    Duloxetine HCl – First approved as an Antidepressant: Cymbalta; later approved in Europe for stress urinary incontinence: Yentreve

  33. newnickname says:

    Suramin: Approved for sleeping sickness (trypanosomes); antihelminthic; a WHO essential medicine.
    Investigated for cancer, autism (very recent: 2014), P2 receptor antagonist, telomerase inhibitor, RNA virus therapy (HIV integrase inhibitor), inhibitor of several GPCRs (inhibits release of Galpha), …
    Suramin goes back to Bayer, 1916, and it sure looks like something from a dye / stain program and not a drug. But Gerhard Domagk didn’t start at Bayer until 1925, 9 years after Suramin.
    It seems to have activity in a lot of areas.  I wonder if it has value for the treatment of ingrown toenails or to fix the Pipeline server?

  34. Jonathan says:

    There was an interesting paper a couple of years ago from Atul Butte on this topic. Most interestingly it flagged cimetidine as a possible therapeutic for some lung cancers:

  35. Hanumantha Rao Madala says:

    Though under trials, Disulfuram, an antabuse, now for cancer with multiple targets like, MGMT, NFkB, Proteasome

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