Relyvrio Discontinued: Top Alternatives and How to Continue Your Treatment

Relyvrio brought a glimpse of hope to ALS patients in the USA with its accelerated FDA approval in 2022. However, the medicine's spark didn't last long. An EMA approval never came after two rejections. And in March 2024, the results of the PHOENIX trial failed to demonstrate Relyvrio's efficacy among a larger population ¹.

It seems inevitable that Relyvrio will be discontinued. However, there are over 4,000 patients in the USA taking the treatment, and perhaps more worldwide that have accessed it via Named Patient Import.

If you're one of them, here's what you should know about Relyvrio's failed clinical trial and your alternatives.

Relyvrio's failed clinical trial: What happened?

When Relyvrio got its accelerated approval in the USA, the FDA did remark on the insufficient evidence that the medicine could help prolong survival or slow the disease progression of ALS patients ⁶. However, at the time there was (and still is) a clear unmet treatment need. Therefore, the FDA decided to move forward with the approval, instead of waiting for the Phase 3 PHOENIX trial results.

Fast forward to the beginning of 2024 and the results of the PHOENIX trial have been underwhelming, to put it mildly. After 48 weeks of treatment, Relyvrio did not show any significant benefit compared to placebo. The clinical benefit was measured by changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) score ¹.

There were also no statistically significant benefits of Relyvrio over placebo on any other secondary outcomes. These included decline in slow vital capacity, quality of life, decline in King’s and Milano-Torino staging, ventilation-free survival, and long-term survival ².

These results have come as a negative surprise to many doctors and patients. Especially given the outcomes of the Centaur trial, where Relyvrio slowed the decline in ALSFRS-R score compared to placebo, particularly in fine motor skills. Patients treated with Relyvrio had a 44% lower risk of death, with a median survival of 25 months compared to 18.5 months for the control group. After 24 months, Relyvrio patients had a 51.6% chance of survival versus 33.9% for the placebo group ⁷.

However, the data are the data. What happens next?

Is Relyvrio being taken off the market?

Yes. On 4 April 2024, Relyvrio's manufacturer Amylyx announced that it had started the process of taking Relyvrio off the market ³. Relyvrio's revocation will apply to both markets where it's approved - the USA and Canada. According to Amylyx's press release, any patients who are currently taking Relyvrio and wish to continue their treatment, will be transitioned to a free program ³.

If you're affected by Relyvrio's removal from the market, here are some of your options and alternatives.

What are your Relyvrio alternatives?

If you or someone you love have been taking Relyvrio, the news of its failed clinical trial must be difficult to deal with. Especially if you had seen good results with it.

However, there are some actions you can take. All of these require a discussion with the treating doctor.

Continue to access Relyvrio via the manufacturer

If you've been satisfied with your Relyvrio treatment and your doctor wishes to keep you on it, you can contact Amylyx to get included in their free program. This can be the best option for you and it won't have any financial consequences, either.

Unfortunately, if you've been taking Relyvrio in a country where it hasn't been approved yet (via the Named Patient Import regulation), the free program may not apply to you. You would have to check with Amylyx and discuss your individual situation with the company.

If you aren't eligible for the free program and would like to stay on Relyvrio, there is another alternative to discuss with your doctor.

Replace Relyvrio with its ingredients (Ammonaps and Tudca)

Relyvrio's active ingredients are sodium phenylbutyrate and taurursodiol. To continue your Relyvrio treatment after the medicine is off the market, you could purchase both active ingredients and take them together.

• Ingredient #1:Tudca. Taurursodiol (also called tauroursodeoxycholic acid) can be purchased under the name Tudca or Tudcabil. Tudca is approved in Italy. It is currently involved in a clinical trial of its own for the treatment of ALS, for which it has been granted an orphan medicine designation by the EMA ⁸. To order Tudca outside of Italy, you can get in touch with our team at Everyone.org. We'll help you purchase and import it as a Named Patient.

Buy Tudcabil

• Ingredient #2: Ammonaps. Sodium phenylbutyrate is available to purchase under the name Ammonaps. It's approved by the EMA and FDA for the treatment of urea cycle disorders. It is not approved anywhere for the treatment of ALS. However, your doctor can prescribe it to you in combination with Tudca for this indication (known as off-label prescription). If you have a prescription, we can help you get the medicine wherever you are.

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Other Relyvrio alternatives

If you have not started your Relyvrio treatment yet, or were not getting the results you wanted, you'd have to explore other alternatives. Below are some options to start the discussion with your doctor.

• Edaravone

  Also known as Radicava or Radicut, this medicine is FDA-approved for the treatment of ALS. Although Edaravone doesn't have EMA approval yet, you could access it from anywhere via Named Patient Import. You will need a prescription from your doctor, though.

  Edaravone is intended to slow the progression of ALS. Clinical studies in Japan have shown that patients treated with Edaravone experienced a slower decline in functional abilities compared to those receiving a placebo ⁴.

  However, some meta-analyses have not found a statistically significant difference in functional ability scores between Edaravone-treated patients and the control group ⁵. Regarding survival outcomes, a recent meta-analysis reported a statistically significant increase in survival rates for ALS patients treated with Edaravone compared to those given a placebo ⁵.

  Whether this medicine could be an option for you is for your doctor to decide.

   

Buy Edaravone

• Rilutek (riluzole)

  Rilutek (riluzole) has been FDA-approved for the treatment of ALS since 1995. It works by modulating the release of glutamate, a neurotransmitter believed to play a role in the neurodegeneration seen in ALS. By reducing glutamate levels, Rilutek aims to slow the disease progression.

  Rilutek is widely available worldwide. However, if it's not approved or available in your country, you can access it anyway via Named Patient Import. Get in touch with our team if you have a prescription for Rilutek, but no access to the medicine locally.

What if a Relyvrio alternative is not available in your country?

ALS patients are (justifiably) frustrated by the lack of treatment options available to them. Equally frustrating is knowing there's an option but having to wait until it's available in your country.

The good news is, any option that is approved somewhere in the world, you can get anywhere via Named Patient Import. Everyone.org specializes in helping patients access the treatments they need regardless of where they are approved. If your doctor decides to replace Relyvrio with its ingredients, switch you to Edaravone, or go for another option, rest assured that you can get the treatment you need.

Simply get in touch with us and send us your prescription. We'll do our best to help you, so that Relyvrio being discontinued doesn't disrupt your treatment.

References:

1. PHOENIX Trial of AMX0035 did not meet endpoints – ALS Society of Canada. ALS Society of Canada, 8 March 2024.
2. Meglio, Marco. Amylyx Mulls Over Pulling AMX0035 Following Disappointing Phase 3 PHOENIX Findings. NeurologyLive, 8 March 2024.
3. Cheng, Mira. ALS drug Relyvrio withdrawn from market after failed clinical trial. CNN, Accessed 14 May 2024.
4. Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686]. NCBI, 14 June 2022.
5. Safety and efficacy of edaravone in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurological Sciences, Accessed 14 May 2024. 
6. Novins, Olivia, et al. Relyvrio Approval: Lessons Learned. Parexel, Accessed 14 May 2024.
7. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. The New Englang Journal of Medicine, Accessed 14 May 2024.
8. EU/3/17/1844 - orphan designation for treatment of amyotrophic lateral sclerosis. European Medicines Agency, 31 March 2017.