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Update on Catalyst Pharmaceuticals

I wanted to update readers on Catalyst Pharmaceuticals, whom I first wrote about here. They’re the ones who have been planning 3,4-diaminopyridine (DAP), a therapy for a rare disorder called Lambert-Eaton Myasthenic Syndrome which is currently being provided at no cost, and run it through the FDA’s regulatory process so as to get market exclusivity for it. The plan then? Charge a lot for it, naturally. Insurance companies will cough up, because there aren’t that many LEMS patients and it’s not worth fighting about, and Catalyst would be able to sit on several years worth of very nice profits with very little risk at all. You may recognize this business plan.

I’ve been blaming the FDA for providing incentives to do this sort of thing, so this latest news is interesting. The agency has sent Catalyst a rare refusal-to-file letter for their drug, saying that the application was incomplete. Further details are lacking, but this is potentially an interesting development.

The press release from Catalyst, by the way, is intensely irritating. They describe themselves as “a biopharmaceutical company focused on developing and commercializing innovative therapies for people with rare debilitating diseases“, but you’ll note that the word “discovering” is not being used, which is good, because they certain didn’t discover DAP as a therapy for this disease. (Here’s a paper from 1989 on the subject, and that one is referencing even earlier studies. No, “commercializing” is the key word, for sure. And the CEO is quoted as saying “We remain focused on delivering on our promise to transform the way people living with LEMS and CMS are provided access to a safe and effective, FDA approved therapy“. My own take on this is that they’re focused on becoming the only people who can say that they took this old therapy and got the FDA to paste an “approved” label on it, thus transforming the way LEMS patients get access by sending them a nice stiff bill for it instead. The DAP patients are getting now, for free, is most unlikely to be any less “safe and effective” than what Catalyst wants to sell them.

But it’s true, Catalyst has promised to transform the way these patients get access, and they’re good for it, too – in fact, I’m sure that they can hardly wait to start transforming things good and hard. The press release, to my eyes, would be greatly improved by the insertion of the phrase “a drug that someone else is willing to provide at no cost” after every mention of the compound. But they seem to have left that part out.

 

44 comments on “Update on Catalyst Pharmaceuticals”

  1. Anchor says:

    It seems to me that this is the battle only the Shkreli’s of the World knows how to fight and win! The FDA and the patient population are helpless. I do not want to be political but is akin to Trump’s Presidential run and nothing could stop him.

    1. Rule (of 5) Breaker says:

      The FDA is not powerless. In fact, they created this mess. Anybody want to take old drugs that have not been through clinical trials and run them through? We’ll give you market exclusivity for a time! Wait, you mean there are people that would actually exploit this loophole to make money? Inconceivable!

  2. a. nonymaus says:

    Behind every discovery, there are people who we must praise. Behind every business decision, there are also people. Let’s not talk about Catalyst Pharmaceuticals, but about the fine people who want to transform the treatment of LEMS and CMS.
    The Board of Directors:
    http://www.catalystpharma.com/directors.shtml
    The C-level management:
    http://www.catalystpharma.com/management.shtml
    The Scientific Advisory Board (Academic MDs who treat LEMS, check for any of your colleagues you might want to have a talk with):
    http://www.catalystpharma.com/advisory-board.shtml
    Let’s see how well McEnany likes being as well-recognized for his contributions to medicine as Shkreli.

  3. Jim says:

    Who is providing the DAP at no cost? Is it being dispensed at compounding pharmacies? I don’t like what Catalyst is going to do (or try to do), but is there any danger of the patients losing their supply if the current model stands?

    1. Mark Thorson says:

      Jacobus Pharmaceutical provides it for free.

    2. Isidore says:

      From the Wikipeadia entry for 3,4-DIaminipyridine:

      Availability
      In the United States, both the phosphate and the free base have completed clinical trials to treat LEMS. Both formulations are available to LEMS patients in the U.S.: the free base is available to patients with LEMS and congenital myasthenic syndromes under a compassionate distribution program by Jacobus Pharmaceutical Company, and the phosphate salt is available to LEMS patients under an expanded access program by Catalyst Pharmaceuticals. Patients must be diagnosed with LEMS or congenital myasthenic syndrome and meet appropriate inclusion criteria.

      Compounding pharmacies may also be a source of amifampridine in the U.S. In Europe, the phosphate is sold by BioMarin, and the free base is compounded, usually by hospital pharmacies.

    3. Will says:

      If Catalyst completes various regulatory testing, the FDA will award it an exclusivity (probably 3 years) and not allow any other company to market the drug

      1. Derek Freyberg says:

        I’m not a regulatory lawyer, but I think that (based on no prior approval), Firdapse would get 5 years exclusivity as an NCE, rather than 3 years.
        The question then is whether the FDA would try to shut down Jacobus and compounding pharmacies. It seems to me that Jacobus would likely find themselves shut down, since they’re a manufacturer – which wouldn’t hurt Jacobus, who are giving the drug away, but would hurt patients; but action against compounding pharmacies would be something else – look at the outcry with the approval of Makena (hydroxyprogesterone caproate) and FDA’s subsequent public concession that it would not proceed against compounding pharmacies. And the price of Makena, as I recall, was only going to be $1700/dose.
        But who knows.
        The refusal to file is interesting, given that Catalyst is the successor to BioMarin on this drug in the US, and BioMarin has an EU approval.

    4. LEMON2 says:

      As others noted, Jacobus Pharmaceutical company provides 3,4 DAP for the cost of shipping only. They have been doing this for 20+ years. They are literally a father-daughter run small pharmaceutical company, but due to the few people with LEMS (only 3 in 1,000,000 people have it) they have compassionately been giving this medicine away in exchange for cooperation from doctors and their patients with LEMS with data collection. I recently was diagnosed with LEMS after 10 years of not knowing the cause of my debilitating illness. Most of us even with medication are only able to work very part time if at all. The idea that Catalyst would have proprietary rights to “their” version of 3,4 DAP has been of us fearful that we may not be able to afford this life changing medication if Catalyst sells it….as for insurance companies covering the cost, that would be great BUT currently I cannot afford some of the medication I need to breathe properly at night, and yes I did say BREATHE! but it is $500/month to buy and i only earn $400/month with my job 1 day a week for whixh it takes me two days to “rest up” and 2 days to reccoperate from…so instead I sleep when I can sitting up but still wake up feeling as if I am being smothered with a 1 ton boulder sitting on my chest. So yes…we are scared that our LIFE saving treatment of 3,4 DAP may become unaffordable and out of reach for us if Catalyst has their way. For some of us it means the difference between living in a wheelchair with 24/7 assistance and being able to walk and care for ourselves.

  4. JG4 says:

    Your use of “good and hard” may be a subtle hat tip to Mencken, who used the phrase to describe democracy.

    1. Derek Lowe says:

      It is indeed! My son, who will just be old enough to vote in the general election this fall, was telling me last night that he thought that quote seemed to apply with extra force this time around. . .

      1. Farmhand says:

        “We move toward a lofty ideal. On some great and glorious day the plain folks of the land will reach their heart’s desire at last, and the White House will be adorned by a downright moron”

    2. Peter S. Shenkin says:

      Mencken famously defined democracy as “The theory that the common people know what they want and deserve to get it good and hard.” However, Mencken did not invent the phrase “good and hard.”

      In The American Language, Fourth Edition, p. 254, he discusses as a general Americanism the use of “good” as “an adjectival reinforcement to adjectives, as in ‘I hit him good and hard’ and ‘I am good and tired’.”

  5. Emjeff says:

    So what should we do? Should we discourage companies from seeking FDA approval for compounds such as DAP, and instead, allow compounding pharmacies to make it for them? It seems like companies are damned if they do and damned if they don’t. If they just marketed the drug without studies, they would be shut down immediately. But, if they go through the long and expensive process of getting FDA approval, then they get slammed for trying to recoup some of their investment. I don’t have the answer, but the situation as it stands is not tenable.

    1. KevinH says:

      The bit where I get stuck is where you’ve written “trying to recoup some of their investment”.

      I think most of us would be happy to see some of these older, grandfathered therapies placed on a firmer basis, with all the systematic testing and analysis of effects and side effects that a modern clinical trial can establish. I also think that most of us can agree that pharmaceutical companies shouldn’t be expected to subsidize such studies.

      However, the problem arises when a company doesn’t seek to merely “recoup…their investment”, but to harvest a massive return far in excess of their costs. These are very-nearly-guaranteed-to-succeed trials; the reward for conducting them is vastly in excess of the cost and risk.

      1. Emjeff says:

        So, how do you control how much a company can charge in a free economy? I always have a problem with the idea that you can determine how much someone is “entitled” to make.

        1. KevinH says:

          I’m afraid that the ship has sailed on calling this a “free market”. Handing out a three-year monopoly on supply and pricing is very much an artificial, non-free situation. Indeed, it’s a very specific, arbitrary, and potent distortion of the (already highly regulated and non-free) pharmaceutical market, designed to encourage specific constructive behaviour. Unfortunately, we’ve seen that in a limited number of edge cases it’s having particularly harmful effects.

          And of course a time-limited monopoly is very much just a sloppy proxy for determining how much a company is “entitled” to make.

          1. Tom B says:

            Amen KevinH. Your line of reasoning is so rarely said out loud in these discussions. The FDA creates the market, with all of it’s rules and contours.
            I always chuckle when folks say that drug prices should be determined by “the market,” conveniently forgetting that giving companies ~20 year monopoly exclusivity on new drugs is a massive intervention in a market.
            It seems to be a case of, the interventions that I like and make me money are the natural and true state of the economy and were handed down by Divine Providence in order to ensure prosperity; whereas the interventions that I don’t like are heavy handed government meddling.

    2. Derek Freyberg says:

      Emjeff, I think you’re missing the point here.
      Firdapse (or at least the active ingredient, diaminopyridine) has been around for a good long time, and has been used in LEMS for a good long time, all without any approvals – I suppose largely because the “market” was so small that no-one sought approval. The compound itself dates to the 1930s, the use in myasthenic syndrome to the 1980s – see the Merck Index or this FDA document: http://www.fda.gov/ohrms/dockets/dockets/98n0182/nom004b.pdf
      So what is happening is that someone (BioMarin, now Catalyst in the US but still BioMarin in the EU) saw this use and figured to run a clinical trial (sure to succeed, one would think), get an approval, and charge what they could for it.
      As KevinH says, it’s not that the Catalysts of this world are trying to recoup costs, it’s that they’re trying (and with the help of the FDA, frequently succeeding) in incurring little risk or cost and making what many people would describe as obscene profits on old therapies.

      1. Emjeff says:

        No, I think you’re missing the point- if you requiring companies to do expensive clinical trials in order to market any compound, then you need to allow companies to make money on the deal. If you want to allow companies to market off-patent drugs without FDA approval, then you don’t get that stamp of approval. You seem to want to have it both ways.

        1. thewonkychemist says:

          So we should allow rent seeking in a small unfree market? Exclusivity is generally a reward for the process of original R&D which is more than just clinical trials. You have a captive market that’s already being provided for. Why should the rent-seeking behavior of companies like this be rewarded? I doubt this was anywhere near the intent of the relevant regulations when they were developed, and it would behove congress or the FDA to do something about it. A company shouldn’t be able to take something that’s been used for years for rare illnesses, run some trials, and gain exclusivity.

        2. Derek Freyberg says:

          I don’t want to have it both ways.
          I want colchicine to have remained on the market it had been on for, what, 100 years, without the FDA handing Mutual/Takeda the right to multiply the price by ten; I want hydroxyprogesterone caproate to have remained on the market without the Makena debacle; and I want Jacobus to be able to continue to supply diaminopyridine for as long as they wish; and so on, and so on – (add scorpion antivenom, tiopronin (Thiola), and several others, including everybody’s favorite Daraprim).
          I am not advocating that new drugs should be brought to market without proper testing, nor that there should be no reward for finding and testing such drugs. What I am saying is that FDA’s insistence on trying to bring all drugs into the post-1962 regime has completely perverted the market for a number of compounds, allowing rent-seeking on an obscene scale.

        3. Thomas says:

          If I want to create an electronic device it will have to go through all kinds of testing for interference, safety, etc.
          None of this gives me any right to exclusivity. If it had exclusivity, it is because of copyrights or patents, not because I have had it tested.

  6. watcher says:

    There seems to one one word missing in their description of the company objectives and goals, and that would be “monetizing, as in “….commercializing, and monetizing innovative therapies…..”

  7. Not sure I’d get that worked up about this. Catalyst is running a phase 3 trial. They are putting money into this.

    If you want a drug to go through a rigorous approval process, you need to provide some inventive for companies to spend the money.

    If you look at the cost of R&D, it’s the D that’s the most expensive.

    And don’t forget Catalyst took some risk bringing this in front of the FDA. Sure there is some data to suggest the srug works, but what if the trial failed? They’re out probably a few millions dollars. You need to reward the risks taken!

    1. HTSguy says:

      Actually, the risk-adjusted cost of lead optimization is very similar to the risk-adjusted cost of a full Phase III development program. So “D” is not the most expensive part of drug discovery/development if you take failures into account.

      1. CMCguy says:

        HTSguy I have apparently have no understanding of what you mean by risk adjusted costing as seen the cost of conducting a single Clinical trial sometimes be greater than the combined Chemistry and Biology Department Budgets, with latter covering multiple targets and projects hence your claim that D is not the most expensive part of drug development makes no sense. Certainly substantially more compounds churned out in Medchem fail to make it out of discovery as lead candidates however the aggregate expense to do that R is relatively low compared to demands for translated from the bench to clinical studies to Marketing Applications.

    2. Tom Womack says:

      If the FDA want the drug to be tested, they should ask Congress for some money with which they pay a CRO to carry out the trial; after which, the drug is tested, still generic, and still available at essentially zero cost. There’s no reason for a profit-seeking pharma company to insert itself in the process!

  8. Pharma Newbie says:

    What really puzzles me is why on earth anyone would take part in such a trial.

    If you are a patient, why would you enroll in such a study?
    Do they get paid to be part of the trial?
    But, even then, what’s the point of getting paid and then eventually ripped off?

    What about the doctors running the trial?
    Are they not aware that the same drug is available for free?
    If they are, don’t they care about the financial well being of their patients?

  9. Sam P says:

    Is DAP a precursor to something else? Expecting a company to provide it free forever doesn’t seem like a viable long-term plan.

    1. SedatedFMS says:

      Great long term plan. Never underestimate the positive image portrayed by such a goodwill gesture. How many other products do they manufacture and supply?

  10. Isidore says:

    How can they be providing this “for free”? Even bulk chemicals have manufacturing, transportation, accounting and other costs, never mind something that must be tested to ensure that it is of adequate quality to go into people.

  11. Magrinho says:

    3,4-diaminopyridine is a bulk chemical and Jacobus probably 1) did not directly invest in LEMS research, 2) has a huge supply that has been qualified for use and 3) has an executive committee of smart, humane, people who feel that it wouldn’t be right on any level to screw sick, vulnerable people to make money.

    1. Mark Thorson says:

      Whoa! Haven’t these people heard of Ayn Rand?

      1. Veylon says:

        Even greedy people – sane greedy people – recognize that goodwill is a worthwhile asset that can be leveraged against other deficits. Sure, giving something away has a cost, but it also has a benefit of making you look good that will cover over the not-look-good stuff you do. “Jacobus isn’t a greedy, nasty corporation! Don’t you know they charitably provide life-saving drugs at no cost? They are saints and heroes!”

  12. Dr. Lloyd T J Evans says:

    An important point which seems to have been missed here: Is it possible for the clinical trials approval procedure for such grandfathered drugs to result in failure? Can the FDA actually refuse to permit continued usage of the drug?

    Since this approval process involves drugs which have been used for many years and are already known to be effective and safe by sheer statistics on usage and patient outcomes, it is extremely unlikely that a clinical trial will show such drugs to be either ineffective or unsafe. At most, all a clinical trial is likely to determine is precisely what dosage is really required and what the best dosage regimen is – how many pills per day for how many days, stuff like that. This is useful information no doubt, but not really critical to the continued usage of the drug. After all, the history of use already provides the same information, just in a more approximate form. So not really a safety or efficacy issue.

    So if this kind of clinical trial cannot fail, where exactly is the risk? As far as I can see, there isn’t any, certainly not for the company which is given the exclusive marketing rights. Yes, they have spent some money on the trials process, but virtually nothing compared to the cost of a proper three-phase trial for a brand new drug. So the reward of pricing power, even if only for a couple of years, yields a near-infinite return on investment.

    This stinks of a boondoggle for the likes of Catalyst, Retrophin, URL Pharma and of course T*ring. Market rigging at its worst, since it is enabled by the FDA itself. Patients are stuck in a classic catch 22 situation. If the weakly powered clinical trials process results in approval (which it will), then they are hit with a whopping increase in price for a drug they were formerly able to buy for little or nothing. If the clinical trials process results in failure (which it theoretically can, but almost certainly won’t), then the FDA withdraws the legal provision of a drug which both patients and doctors damn well know works, for no particularly good reason.

  13. Anon says:

    What if the trial actually fails to show a significant effect? Which is entirely possible if the trial is underpowered or conducted poorly, or just by pure chance. Does that mean the current free product would have to be withdrawn?

    1. exGlaxoid says:

      I have known of at least one clinical trial of an eye drop medicine, which the FDA dragged out for many years, of a well known, existing USP compound, but in a new formulation, which the FDA eventually failed to approve, due to their inability to understand that some side effects can be handled if the treatment prevents a worse case. I was in the trial and got free medicine for several years under it. But that formulation is no longer available, and the small company, founded solely to make it, went under. So it has happened, and the FDA did not do anything for the people who got a benefit from the drug. But it is a rare occurrence, for sure.

      But I agree that there should be some reasonable parameters on taking a known drug and testing it for future use. Perhaps the NIH should have looked at the grandfathered drugs (on the market before the FDA rules came in to play) and simply done some clinical trials to put them into the public domain for any generic company to sell. Or the FDA could specify a price (or ROI) that older drugs could be sold for under the new rules. Europe does that currently. But the politicians in this country are too busy trying to raise money and get re-elected to do their jobs well.

      There are few limits on compounding pharmacies, so almost any of these drugs can be formulated by them, under the current rules, so anyone who needs them could go and get them made for them, or even buy them overseas and bring them back. I have seen an alternate (lower conc.) formulation of the drug I used that is OTC, which is widely used by people for the same condition. The challenge is that most US patients are not aware or able to find ways to find their drugs in alternate forms. It would be nice if the FDA would at least help allow compounding pharmas to provide them if the current source stops making it or jacks the price up.

  14. idiotraptor says:

    An engaging series of posts.

    @ a.nonymous #3

    Thanks for posting links. Loathsome individuals all. My sentiment is that if readers find the actions and behavior of Catalyst Pharmaceuticals’ executive management, BOS, and SAB professionally and ethically objectionable (certainly do), then make their lives as difficult and as uncomfortable as legally permissible.

  15. Derek, I think your picture of Catalyst Pharmaceuticals is incomplete at best. They have licensed GABA-aminotransferase inhibitors from Rick Silverman’s lab, and it looks like they are supporting preclinical studies with these compounds for PTSD and other disorders:

    http://www.catalystpharma.com/cpp-115.shtml

    This certainly appears to be legitimate (and risky) drug discovery, the 3,4-diaminopyridine gambit notwithstanding.

    1. Phil says:

      Chris, you may be right that DAP isn’t the whole story, but their legitimate drug discovery programs don’t excuse the rent-seeking for DAP. It’s an ends-justify-the-means argument that Shkreli has also used (we’re going to use this Daraprim money to fund original drug discovery!).

  16. Bill says:

    The problem with many of the comments are that they ignore the fact that Firdapse is a more stable formulation of 3,4 DAP. The freebase form available “free” from Jacobus has not received any review from the FDA, in spite of it being used for 20 years for LEMS. Jacobus has Phase II results, but only in poster form with few details. Firdapse is more stable and more rigorously studied, with published endpoint values from a Phase III study. The RTF is clearly a concern given that the pre-NDA meeting occurred last Feb and submission was on a rolling basis. Note also that Firdapse was granted Breakthrough status. That is also something 3,4 DAP from Jacobus does not have. Furthermore, there are extensions such as CMS that are also undergoing FDA clinical trials. As most should know, a drug is not simply defined as the API, so there is value in a proven, FDA approved form with better overall stability over the freebase compounded in a former nuclear lab that has been sited several times for safety violations including receipt of a warning letter FDA File No: 97-NWJ-52. So, before condemning a company for attempting to properly develop an effective medicine (not just repackaging an old one) it’s probably best to more fully understand the specifics.

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