Firdapse Oral Therapy Expected to Become LEMS’ Treatment of Choice, Review Says

Firdapse Oral Therapy Expected to Become LEMS’ Treatment of Choice, Review Says

Scientists believe Firdapse (amifampridine phosphate) will soon become first-line management therapy for Lambert-Eaton myasthenic syndrome (LEMS), due to its stability, low-dose variability, good tolerability, and effectiveness, a review says.

The study, “Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug,” was published in Annals of Pharmacotherapy.

The mainstay for symptomatic treatment of LEMS is 3,4-diaminopyridine (3,4-DAP). However, despite its long history as a LEMS first-line treatment, the therapy was never formally approved by the U.S. Food and Drug Administration (FDA). That was due to issues with variability, and reliability of the product between batches. Because of this, 3,4-DAP was modified into a salt formulation called amifampridine phosphate.

Firdapse, developed by Catalyst Pharmaceuticals, is an oral prescription therapy for patients age 17 and older for the symptomatic treatment of LEMS. It was cleared by the FDA less than a year ago, in November 2018. The treatment restores the communication between muscle cells, thus improving patients’ muscle function.

To learn more, researchers at the OhioHealth Riverside Methodist Hospital reviewed all available literature on both 3,4-DAP and amifampridine phosphate for the treatment of LEMS. They used three biomedical databases, and searched the literature for the following terms: “amifampridine,” “3,4-diaminopyridine,” and “Lambert-Eaton myasthenic syndrome.” Studies included in the review had to feature human subjects aged 18 or older, and be Phase 2 or 3 clinical trials.

Six clinical trials, including a total 105 participants, were used to evaluate the impact of varying doses of 3,4-DAP in LEMS.

In general, the therapy was seen to improve muscle function, as well as muscular strength, and reduce patients’ disability and disease severity. In some of the studies, 3,4-DAP was associated with adverse effects like lightheadedness and heavy headedness, epigastric discomfort (meaning “in the upper abdomen, below the ribcage but above the intestines”), seizures, and digital and perioral numbness or tingling sensation (paresthesia).

On the other hand, two placebo-controlled Phase 3 studies (NCT02970162 and NCT01377922) have confirmed amifampridine phosphate is well-tolerated and effective in managing disease symptoms. “No reported adverse effect in either trial was considered to be serious or attributed to treatment,” the researchers said.

Nonetheless, the treatment has been associated with a dose-dependent increased risk of seizures. As such, the therapy is contraindicated in people with a history of seizure activity.

Compared with 3,4-DAP, amifampridine phosphate has an improved stability profile and decreased dose variability, making it more attractive both for medication prescribers and LEMS patients. In pharmacology, stability refers to the extent to which a given medicine retains — within specified limits and throughout its period of storage and use — the same properties and characteristics that it possessed at the time of its manufacture.

“[A]mifampridine will likely assume the role of first-line management of LEMS,” the investigators said.

The recommended initial dose of amifampridine phosphate is 15 to 30 mg once a day, taken in three to four divided doses without regard to meals. Each single dose should not exceed 20 mg, and the maximum total daily dosage should be below 80 mg. That is due to therapy-related risk of seizures.

“Prior to the approval of Firdapse, 3,4-DAP was provided to patients at no cost by Jacobus Pharmaceuticals under a compassionate use program. Firdapse is now the only available formulation of 3,4-DAP and is estimated to cost more than $300000 annually,” the researchers said. ” With the approval of Firdapse, cost may be of concern because patients were previously receiving 3,4-DAP free of charge,” they added.

Nonetheless, “Practitioners should familiarize themselves with Firdapse because this agent is now the only available formulation of 3,4-DAP for adults,” the study concluded.

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.
With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.
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  1. Jerry Hirsch says:

    I was initially diagnosed with LEMS around 3 years ago, after many other misdiagnosis by local neurologists who diagnosed me with POSSIBLE Parkinson’s, non-Hodgkin’s lymphoma, M.S., and a host of other possibilities which turned up negative with further tests! Finally, I went to the MAYO Clinic, and the neurology dept performed a test that the others did not… An “EMG”, which confirmed LEMS.
    Upon returning home, and doing online research, I found out about the clinical trial being done by Catalyst Pharm. I contacted them, and volunteered to participate in the study. I was accepted, and was given their Firdapse (at that time known as 3-4 DAP) on the 1st day of my participation. It was supposed to be a double blind study, but I knew within an hour that I wasn’t given a placebo! When I arrived at the clinic, I was in a wheelchair, barely able to lift my feet off the ground. An hour after taking my 1st dose (4 x 20mg/ day) I was able to stand up, and use a walker (for balance) to get around. Now, after taking the drug for almost 3 years, I usually just use a cane for short trips, and my current (LEMS related) issues are general weakness, fatigue, tingling feeling on my face, tongue, and soles of my feet! I assume that these are some of the side effects of Firdapse, but they are a lot better than needing a wheelchair to get around! Thank you Catalyst Pharm!

    • Jacque says:

      I am happy you found a solution to treating your LEMS. I have one question if you don’t mind. Wasn’t 3,4 DAP available to you at that time from Mayo Clinic. I know others who got it years prior to you being there. Thanks.

  2. Jacque says:

    As a LEMS patient I can attest this is an absolute lie. 3,4 DAP was 100 percent more effective without the terrible side effects than Firdapse. Since being forced to take Firdapse I among numerous others have required medical intervention and a loss of quality of life. Who paid you to write this article full of lies? Catalyst Pharmaceutical has comprised my health considerably with their medication which is NOT the same as DAP. There are numerous LEMS patients who will be happy to validate this. I am fighting to get Ruzurgi in order to stay alive I will go public with this issue. Through television news and social media. How dare you assume you know what works for those of us who actually require the medication.

  3. Vickie Moored says:

    If 3,4 DAP have SO many problems that the FDA didn’t approve it, why then did they approve Ruzurgi (same as 3,4 DAP)for children? Get your facts straight. There are many errors in this article. I know, I am a LEMS patient that has been on both 3,4 DAP and firdapse.

    • Pontaeus says:

      Because Bernie Sanders is running for president and cheap drugs are part of his platform and “pharma is evil” is a simple message for the masses. Bernie put huge pressure on the FDA and they caved and approved 34DAP on data from less than 20 people gathered over 3 decades. That’s how it got approved. Jacobus had 3 decades to get their act together and submit their file and they couldn’t. Fact.

      • Jacquelyn Rosser says:

        They need that pressure. Pharmaceutical companies are killing people. 3,4 DAP is 100 percent more effective than Firdapse. I know I’ve taken both. The FDA should never have allowed Catalyst to patent an orphan drug. I am ecstatic Ruzurgi is now available. Thank you Bernie Sanders and all of the LEMS patients who fought for this.

  4. Julie says:

    Firdapse is like a sugar pill!! It’s awful and slowly killing my husband!! You should be ashamed on soo many levels!! Bring back the REAL 3,4 Dap before he is no longer able to move!!

  5. Deb Maure says:

    Seems to me this article was sponsored by Catalyst. I’ve had LEMS for 10 years and have been in contact with fellow sufferers worldwide (thanks to Facebook). The overwhelming opinion of my fellow Lemons and myself is that 3,4 DAP is a godsend and that Firdapse is a greedy pharmaceutical company’s cash cow. Disgusting.

  6. Ann Schuller says:

    Talk to LEMS patients and they will happily tell you about their “miracle moment”. Jerry Hirsch commented here, sharing his moment with Firdapse. My son had his with 3,4 DAP. Like Jerry, my son was in a wheelchair and 40 minutes after taking his first dose of DAP, he was up doing deep knee bends. When you have an experience as life changing as that, it is hard to severe ties with the drug and the company that quite literally gave you your life back. Knowing this, you can understand why some of the comments left here are so emotional. My son switched from DAP to Firdapse earlier this year following its FDA approval. There was no other choice. But now Jacobus has received approval for its DAP drug, renamed Ruzurgi, to treat pediatric LEMS patients. My son is an adult, but his neurologist prescribed Ruzurgi “off-label” to treat his LEMS knowing that it had been working just fine for him for five years. Our insurance company was happy to pay for it because it was less than half the cost of Firdapse. The LEMS community now has options and should consider both drugs. Choice is a good thing.

  7. Linda says:

    As a patient that has been taking Jacobus 3,4 dap for over six years, I can tell you that this article is full of untrue statements.
    Price is not a factor for me. I could have either Firdapse or Ruzurgi, the FDA approved medication that Jacobus makes. I chose to stay with the Jacobus drug after hearing so may horror stories from fellow Lems patients who have had to give up daily activities, turn to additional forms of treatment, had horrible side effects and some even were hospitalized after switching to Firdapse.

    I received my prescription for Ruzurgi ,so that I do not have to suffer the ill effects and further compromise to my health and quality of life that a significant amount of Lems patients are enduring from Firdapse.

    This fictional account you have written is a prime example of how Catalyst Pharmaceuticals operates, and for that reason alone, I would not take their drug even if the Jacobus, drug were not available.
    So many are suffering from lack of effectiveness, side effects, or both, and Catalyst does not acknowledge in any way the onslaught of reports addressing this problem.

    Catalyst did not save us, they blocked our use of the drug that works, and substituted their inferior one. We will continue to fight this injustice until every patient has been restored to their previous state of well being that this travesty has brought about.

    • Jose says:

      Linda you do not have all the facts. All side effects must be reported to the FDA. Any patient can report them to the FDA directly as I have with a cholesterol medication I was on. If a drug is as bad as you claim it would be taken off the market. A company cannot block another drug. Only the FDA can do that. There is no injustice, your doctor can write a prescription for any drug, on or off-label. I was on 3,4 dap made up in a pharmacy and now I am on Firdapse and it’s working fine.

  8. Patricia Lempert says:

    Hello Everyone ,

    I am a Lems patient for numerous years .
    & I have just recently started Firdapse Medication .
    It is the first and only medication I have tried to help treat my Lems disease.

    Now After Screaming for many years that something was wrong with me .
    I finally got a Dr to really take his time and to listen to me .
    Yes it was confirmed I have
    Lambert Eaton Syndrome.

    I have just started taking Firdapse For three weeks now & I’m Still on the fence about how I truly feel .

    I have no allegiance to any political parties or pharmaceutical companies .

    I’m simply a human being looking for either a cure or a effective treatment.

    I hate being brainwashed by reviews & comments
    However, you never know whether their alliance is truly coming from a true LEMS patient or is it a pharmaceutical company or some other company looking to make a false review – just for profit .

    I can tell you all I’m a 49 year old woman who has nothing to lose & much in Life to gain if I can only live with out pain , weakness , & fatigue.

    Firdapse now has some Great/ weird effects.
    I started out in baby steps .
    Taking only 5mg
    3 to 4 times a day .
    Then 10 mg
    3 to 4 times a day .
    Last & not least
    However only 2 times a day .

    Now even though the lower doses were 4 times a day I only felt a very little difference.
    Taking 20 mg 2 x a day I feel much less weakness in my legs yet let me share that it is NOT with out side effects.

    At 5 mg
    I only felt tired a little.
    And nauseous from time to time .

    Now at 20 mg
    I have nauseous ,dizziness & a weird tingling in my hands ,
    lips and my feet .

    But I can say I do move much better taking this medication.

    Is it they BEST ?
    but does it help YES .

    I would like say to ALL the research companies out there.
    Thank you for this medication, however , you need to improve the effects .

    It’s great I can move a little less freely – but I want to NOT feel tingling & and nauseous every single day of my life .

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