Relyvrio's elusive approval in Europe: How to skip the wait

NOTE: This article was written before April 2024, when Relyvrio's manufacturer Amylyx announced that it would be pulling Relyvrio from the market. In light of this development, a Relyvrio EMA approval is unlikely to come. Instead, discuss some Relyvrio alternatives with your doctor. 

For decades, ALS patients in Europe have not seen any new medicine approvals. In 2023, Relyvrio provided a glimpse of hope for changing the ALS treatment landscape. After securing FDA approval, the medicine was on track for approval in Europe, until the CHMP rejected its application. Twice.

While medical approval authorities are simply doing their job being thorough, ALS patients are left with the frustration of waiting. Facing a lack of treatment options while racing against time, some have even resorted to mixing their own medicines ¹.

There are better solutions than this. Here's everything you need to know about Relyvrio's approval in Europe. Including the safe and quick options you have to get the treatment quickly.

What does Relyvrio/Albrioza do?

Relyvrio (marketed in Europe as Albrioza) is an oral medicine for adults with ALS. It combines two active ingredients - taurursodiol and sodium phenylbutyrate. Its exact mechanism of action isn't well understood. However, it's designed to prevent nerve cell death by blocking stress signals within two cellular compartments (mitochondria and the endoplasmic reticulum).

Relyvrio/Albrioza isn't a cure for ALS. Even so, clinical trial results suggest that it may help slow down the disease progression and help patients maintain physical functions for longer ².

Is Albrioza/Relyvrio effective?

Albrioza/Relyvrio's FDA approval was based on results from the CENTAUR clinical trial. The first phase of the trial compared Relyvrio with placebo to establish its safety and efficacy. The second phase of the trial focused on the long-term safety of the treatment.

The key outcomes from this trial were:

• Relyvrio slowed the rate of decline in the ALSFRS-R score vs placebo (1.24 points vs 1.66 points). This result was most prominent in fine motor skills ⁴;
• The risk of death was 44% lower for patients treated with Relyvrio vs placebo;
• Median survival was 25 months for the Relyvrio group and 18.5 months for the control group;
• At 24 months after start of treatment, Relyvrio patients had an estimated 51.6% chance of survival compared to 33.9% for the placebo group ³.

Results of the CENTAUR trial have been interpreted positively by the FDA, but there are limitations to the study. These limitations have contributed to Relyvrio's EMA rejection. The PHOENIX phase 3 clinical trial is currently ongoing, with an intention to confirm Relyvrio's efficacy and survival benefits. Hopefully, it will provide additional evidence to support a re-application to the EMA. The results of the PHOENIX trial are expected in 2024 ⁵.

Why was Relyvrio refused EMA approval?

As a patient, you're probably wondering why a treatment that is considered efficient enough by one agency is rejected by another. Medicine approval criteria and stringency differ across countries. And the EMA tends to be one of the stricter agencies out there.

When rejecting Relyvrio/Albrioza's application, the CHMP cited concerns regarding the medicine's efficacy and clinical trial data reliability. The commission was not convinced that Albrioza was effective in slowing down ALS progression. Their conclusion was that a positive benefit-risk balance could not be established ₆.

When will Relyvrio/Albrioza be available in Europe?

Despite the disappointment of the EMA rejection, Albrioza/Relyvrio's manufacturer is committed to addressing the concerns raised by the EMA and reapplying for approval. Hopefully, the PHOENIX trial results will be able to support that application in a positive way.

Typically, a marketing authorization application to the EMA takes about 210 days to review. However, Relyvrio has an orphan drug designation. This means that a potential reapplication with stronger evidence may be eligible for a faster review or conditional marketing authorization ⁷.

In any case, it doesn't seem likely for Relyvrio/Albrioza to be available in Europe within 2024.

How to get Relyvrio/Albrioza before its EMA approval

As Sabine Turgeman, head of the French Association for Research into ALS put it, "The disease is not on bureaucratic time"[1]. So even if we are a year away from Relyvrio's EMA approval (fingers crossed), that may still be a frustratingly long time for patients.

The good news is, you don't have to wait for approval. 

You have two options to start your Relyvrio treatment before the medicine is available in Europe. One option is to find and join a clinical trial involving Relyvrio/Albrioza. The other option is to buy Relyvrio right away as a Named Patient. 

Here’s what each of these options means.

Join a Relyvrio clinical trial

You can try joining an ongoing clinical trial to get quick access to Relyvrio/Albrioza. Finding trials isn't easy, but it's possible. To participate, you must meet the eligibility criteria and have your doctor's support. Be aware that you might receive a placebo instead of the active ingredient.

Here are some good places to start looking for ongoing Relyvrio clinical trials:

• ClinicalTrials.gov: This is a database with all clinical trials in the USA. However, some of the trials are also open to international participants. At the moment, there is one trial (NCT05619783) involving Relyvrio and recruiting international participants by invitation. However, it's worth keeping an eye on this list, as new trials may become available at any time.
• EUClinicaltrials.eu: This database contains all clinical trials in the European Union. Currently, it contains limited information on trials launched before 31 January 2022. For those trials, you can refer to the EU Clinical Trials Register.
• myTomorrows and FindMeCure: These organizations suppor patients in finding treatment options in clinical trials.

Buy Relyvrio as a Named Patient

If joining a clinical trial isn’t an option for you, you can buy Relyvrio/Albrioza right away as a Named Patient. This is made possible thanks to the Named Patient Import regulations in place in most countries. To make use of these regulations, you need to have a prescription for Relyvrio/Albrioza from your treating doctor.

Buy capivasertib

Already have a prescription? Send it to our team of Medicine Access experts and we'll support you in buying Relyvrio immediately. Wherever you are based.

Ultimately, the decision to seek access to Relyvrio/Albrioza before its EMA approval is between you and with your doctor. It's essential to approach this process with realistic expectations and a thorough understanding of the potential risks and benefits involved. This being said, when you're ready to start your treatment, our team is here to help you skip the wait.

References:

1. Every month counts: European ALS patients want new drugs. France 24, 28 February 2023.
2. Why RELYVRIO. RELYVRIO.com, Accessed 13 February 2024.
3. Long‐term survival of participants in the CENTAUR trial of sodium phenylbutyrate‐taurursodiol in amyotrophic lateral sclerosis. NCBI, Accessed 13 February 2024.
4. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. The New England Journal of Medicine, 3 September 2020.
5. Relyvrio for ALS. ALS News Today, Accessed 13 February 2024.
6. Albrioza | European Medicines Agency. European Medicines Agency, Accessed 13 February 2024.
7. Orphan designation: Overview | European Medicines Agency. European Medicines Agency, Accessed 13 February 2024.