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Disease-Modifying Therapies for ALS

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FDA-approved disease-modifying therapies for ALS, such as Riluzole, Edaravone, and Tofersen, aim to slow disease progression rather than cure it. These medications offer modest benefits but require careful consideration of their administration schedules, side effects, and genetic eligibility.

Key Takeaways

  • • Disease-modifying therapies for ALS aim to slow the progression of the disease but are not cures.
  • • Riluzole modestly slows progression but requires regular blood tests to monitor liver function.
  • • Edaravone can slow the loss of physical function but involves a rigorous, cyclic daily dosing schedule.
  • • Tofersen is a specialized medication administered via spinal tap for patients with the SOD1 genetic mutation.
  • • Relyvrio was voluntarily withdrawn from the market in 2024 and is no longer an available treatment option.

The landscape of ALS treatment is evolving, with several FDA-approved medications designed to slow the progression of the disease. While these are not cures, they are “disease-modifying,” meaning they aim to change the course of the illness rather than just manage symptoms [1][2].

Currently Available Treatments

There are three primary disease-modifying therapies currently approved for use in the United States. It is critical to weigh their modest benefits against the practical burdens of taking them.

  1. Riluzole: Approved in 1995, this was the first drug shown to impact the course of ALS [3].

    • How it works: It is a glutamate modulator that blocks the release of excess glutamate, a chemical that can become toxic to motor neurons [4].
    • What to expect: It has been shown to modestly slow disease progression and can extend survival by a few months [5].
    • Important Considerations: Patients taking Riluzole require regular blood tests to monitor liver function (liver enzymes), as the medication can cause liver inflammation [5][3].

  2. Edaravone: Approved in 2017, this drug is available as both an intravenous (IV) infusion and an oral liquid [3].

    • How it works: It acts as a free radical scavenger to protect motor neurons from “oxidative stress” [6][7].
    • What to expect: In clinical trials, it was shown to slow the loss of physical function in certain ALS patients [3][6].
    • Important Considerations: Edaravone requires an intensive cycling schedule (e.g., 14 days of daily dosing, followed by 14 days off), which can be a significant logistical burden for patients and caregivers [3].

  3. Tofersen: Approved in 2023, this is a highly specialized treatment for a specific genetic form of the disease [8].

    • How it works: It is an antisense oligonucleotide (ASO) designed specifically for people with a mutation in the SOD1 gene [9][10].
    • What to expect: It can significantly reduce levels of nerve damage markers (like neurofilament light chain) and slow functional decline over time [11][12].
    • Important Considerations: Tofersen is administered through a lumbar puncture (spinal tap), which carries risks of back pain, headaches, and more severe neurological issues like myelitis or radiculitis (inflammation of the spinal cord or nerve roots) [13][12].

Important Update: The Withdrawal of Relyvrio

If you are searching for information online, you may see mentions of a drug called Relyvrio (also known as AMX0035). It is important to know its current status to avoid confusion. Relyvrio received “accelerated approval” from the FDA based on early phase 2 data [14][15]. However, the larger Phase 3 trial called PHOENIX demonstrated that the drug did not significantly slow the disease or improve quality of life compared to a placebo [16][17]. Based on these results, the manufacturer voluntarily withdrew the drug from the market in 2024 [18][19]. Relyvrio is no longer available as a treatment for ALS.

Clinical Trials

Because current therapies offer modest benefits, many patients choose to participate in clinical trials to access experimental treatments. Organizations like the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) are excellent resources for finding active trials that you may be eligible for [2][20].

Frequently Asked Questions

What are disease-modifying therapies for ALS?
Disease-modifying therapies are medications designed to alter the course of ALS and slow its progression. While they are not cures, they can help preserve physical function and extend survival time for some patients.
What are the side effects of Riluzole?
Riluzole can cause liver inflammation, so patients taking this medication require regular blood tests to monitor their liver enzymes. Your care team will track these results closely to ensure the drug remains safe for you to use.
How is Edaravone administered?
Edaravone is available as both an intravenous (IV) infusion and an oral liquid. Both forms require an intensive cycling schedule, typically involving 14 days of daily dosing followed by 14 days off.
Who is eligible for Tofersen?
Tofersen is a highly specialized treatment specifically designed for ALS patients who have a confirmed mutation in the SOD1 gene. Your doctor will need to order genetic testing to determine if you are a candidate for this medication.
Is Relyvrio still available for ALS patients?
No, Relyvrio is no longer available as a treatment for ALS. The manufacturer voluntarily withdrew it from the market in 2024 after a large Phase 3 clinical trial showed it did not significantly slow the disease or improve quality of life.

Questions for Your Doctor

  • • Am I a candidate for Riluzole or Edaravone, and what are the realistic benefits I can expect from these treatments?
  • • Has my genetic testing come back for the SOD1 mutation? If so, should we discuss starting Tofersen?
  • • What are the specific side effects and monitoring requirements (like blood tests) for the medications you're recommending?
  • • Given the rigorous cycle of Edaravone, does the oral form make more sense for my lifestyle than the IV infusion?
  • • Can you refer me to resources like the NEALS consortium to help me find a clinical trial?

Questions for You

  • • How do I feel about the potential benefits versus the side effects of the currently available medications?
  • • Am I prepared for the rigorous administration schedules, such as regular blood tests or cyclic dosing?
  • • Am I interested in participating in clinical trials to access experimental therapies?

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References

  1. 1

    Novel Selenium-based compounds with therapeutic potential for SOD1-linked amyotrophic lateral sclerosis.

    Amporndanai K, Rogers M, Watanabe S, et al.

    EBioMedicine 2020; (59()):102980 doi:10.1016/j.ebiom.2020.102980.

    PMID: 32862101
  2. 2

    Prevalence of Amyotrophic Lateral Sclerosis - United States, 2015.

    Mehta P, Kaye W, Raymond J, et al.

    MMWR. Morbidity and mortality weekly report 2018; (67(46)):1285-1289 doi:10.15585/mmwr.mm6746a1.

    PMID: 30462626
  3. 3

    Edaravone: a new hope for deadly amyotrophic lateral sclerosis.

    Bhandari R, Kuhad A, Kuhad A

    Drugs of today (Barcelona, Spain : 1998) 2018; (54(6)):349-360 doi:10.1358/dot.2018.54.6.2828189.

    PMID: 29998226
  4. 4

    Riluzole and Edavarone: The Hope Against Amyotrophic Lateral Sclerosis.

    Rokade AV, Yelne P, Giri A

    Cureus 2022; (14(10)):e30035 doi:10.7759/cureus.30035.

    PMID: 36381733
  5. 5

    Current Therapy of Drugs in Amyotrophic Lateral Sclerosis.

    Lu H, Le WD, Xie YY, Wang XP

    Current neuropharmacology 2016; (14(4)):314-21 doi:10.2174/1570159x14666160120152423.

    PMID: 26786249
  6. 6

    Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis.

    Cho H, Shukla S

    Pharmaceuticals (Basel, Switzerland) 2020; (14(1)) doi:10.3390/ph14010029.

    PMID: 33396271
  7. 7

    Ethnical Disparities in Response to Edaravone in Patients With Amyotrophic Lateral Sclerosis.

    Jayasinghe M, Jena R, Singhal M, et al.

    Cureus 2022; (14(6)):e25960 doi:10.7759/cureus.25960.

    PMID: 35855239
  8. 8

    Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis.

    Karros M, DiFulco M, Nogid A

    The Annals of pharmacotherapy 2026; 10600280251408862 doi:10.1177/10600280251408862.

    PMID: 41640104
  9. 9

    Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations.

    McGuigan A, Blair HA

    CNS drugs 2025; (39(9)):903-912 doi:10.1007/s40263-025-01204-5.

    PMID: 40640528
  10. 10

    Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.

    Miller T, Cudkowicz M, Shaw PJ, et al.

    The New England journal of medicine 2020; (383(2)):109-119 doi:10.1056/NEJMoa2003715.

    PMID: 32640130
  11. 11

    Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.

    Miller TM, Cudkowicz ME, Genge A, et al.

    The New England journal of medicine 2022; (387(12)):1099-1110 doi:10.1056/NEJMoa2204705.

    PMID: 36129998
  12. 12

    Profiling tofersen as a treatment of superoxide dismutase 1 amyotrophic lateral sclerosis.

    Oliveira Santos M, de Carvalho M

    Expert review of neurotherapeutics 2024; (24(6)):549-553 doi:10.1080/14737175.2024.2355983.

    PMID: 38758193
  13. 13

    Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.

    Miller TM, Cudkowicz ME, Shaw PJ, et al.

    JAMA neurology 2026; (83(2)):115-125 doi:10.1001/jamaneurol.2025.4946.

    PMID: 41661214
  14. 14

    An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis.

    Sun Y, Li X, Bedlack R

    Expert review of neurotherapeutics 2023; (23(1)):1-7 doi:10.1080/14737175.2023.2174018.

    PMID: 36705941
  15. 15

    Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.

    Paganoni S, Macklin EA, Hendrix S, et al.

    The New England journal of medicine 2020; (383(10)):919-930 doi:10.1056/NEJMoa1916945.

    PMID: 32877582
  16. 16

    Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.

    Ketabforoush A, Faghihi F, Azedi F, et al.

    Clinical drug investigation 2024; (44(7)):495-512 doi:10.1007/s40261-024-01371-1.

    PMID: 38909349
  17. 17

    Ultra-high dose methylcobalamin and other emerging therapies for amyotrophic lateral sclerosis.

    Kaji R, Izumi Y, Oki R

    Current opinion in neurology 2024; (37(5)):593-602 doi:10.1097/WCO.0000000000001311.

    PMID: 39083229
  18. 18

    Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States.

    Calcagno N, Scirocco E, Clampffer E, et al.

    European journal of neurology 2025; (32(9)):e70360 doi:10.1111/ene.70360.

    PMID: 40965373
  19. 19

    A single ALS center experience with clinical use of sodium phenylbutyrate-taurursodiol.

    Quinn C, Baer M, Amado DA, et al.

    Muscle & nerve 2024; (70(1)):148-151 doi:10.1002/mus.28096.

    PMID: 38670927
  20. 20

    [Gold Coast Criteria: A New Diagnostic Paradigm in the Era of Disease-Modifying Therapy for Amyotrophic Lateral Sclerosis].

    Yamakawa I, Urushitani M

    Brain and nerve = Shinkei kenkyu no shinpo 2024; (76(11)):1217-1223 doi:10.11477/mf.1416202763.

    PMID: 39523614

This page provides educational information about ALS disease-modifying therapies. Always consult your neurologist to determine the safest and most appropriate treatment plan for your specific diagnosis.

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