AMX0035 Approved! How We Got Here and What Comes Next

Blog post from the ALS Association. View Original Source.

In the summer of 2014, millions of us took part in the ALS Ice Bucket Challenge. Celebrities, friends and family members all dumped ice on their heads to help raise awareness and funds for ALS. Thanks to everyone who donated, new ALS genes were discovered, new global research projects were funded and care services were expanded to help more people with ALS.  

One of the potential treatments that the ALS Association funded was AMX0035, which was first imagined by two Brown University students in a dorm room the year before the Ice Bucket Challenge.  

The ALS Association spent over $2 million helping fund the development and clinical trial of AMX0035. When the results of that trial showed it was safe and effective in treating ALS, the ALS Association led an advocacy campaign to push the FDA to approve the drug. After two years of advocacy, the FDA finally approved AMX0035. 

“This is a victory for the entire ALS community, which came together to advocate for early approval of AMX0035. We still have a lot of work to do to cure ALS, but this new treatment is a significant step in that fight,” ALS Association President and CEO Calaneet Balas said in a statement.  

In September of 2020, The ALS Association and I AM ALS submitted over 50,000 signatures to the FDA calling on the agency to approve AMX0035. In subsequent months, the Association held multiple meetings with FDA officials, including a public We Can’t Wait Action Meeting in May of 2021, so members of the ALS community could speak directly to FDA officials. The Association also provided scientific and regulatory guidance and in 2022, drove over 14,000 individual emails to the FDA urging approval. 

Steve Kowalski, who was diagnosed with ALS in 2017, testified twice before the FDA’s advisory committee pleading for quick approval.  

“This is a positive step forward on that path to making ALS a livable disease until we find a cure. It means the possibility of increasing precious time with friends and family, greater independence and improving the quality of life for people living with ALS today,” he said of the decision.  

Sunny Brous, a dedicated advocate for swift approval of safe and effective treatments, also celebrated the approval of AMX0035.  

“When I took the Ice Bucket Challenge, I never imagined I would be diagnosed with ALS a few months later at the age of 27. Approval of AMX0035 is a shared victory for everyone living with ALS, and a tribute to those we’ve lost. We can agree this disease is different for everyone and approval means a new line of defense while moving us one step closer to making ALS a livable disease,” she said. 

Before AMX0035 will be made available, payers like Medicare and private insurance companies have to make determinations on whether and how they will cover the drug.  

For more on how insurance coverage decisions are made, listen to this discussion on Connecting ALS.

This is a hugely meaningful win for the community. Getting effective new drugs approved and made available as quickly as possible is key to making ALS a livable disease. Thanks to everyone who worked tirelessly to make this happen, and to everyone who took the ALS Ice Bucket Challenge.  

What is AMX0035 (RELYVRIO)?

AMX0035 is an investigational drug, also known as RELYVRIO or PB/TURSO. AMX0035 is a combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO). 

How does AMX0035 work?

AMX0035 is an investigational drug, also known as RELYVRIO or PB/TURSO. AMX0035 is a combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO). 

How is AMX0035 administered?

AMX0035 comes in sachet packets of a powder that is dissolved in room temperature water. It can be administered by mouth or by feeding tube. In the phase 2 trial, the dose regimen was to take the drug once daily for first three weeks and then twice daily if tolerating. 

What have researchers learned about AMX0035 so far?

Amylyx published a peer-reviewed paper in the New England Journal of Medicine outlining the results of the CENTAUR phase 2 trial and another outlining the trial’s  overall survival data in the journal Muscle and Nerve.

Overall, the trial enrolled 137 people with ALS in 25 medical centers through the Northeast ALS (NEALS) Consortium from June 2017 to September 2019. It showed that AMX0035 was well-tolerated and there were no major safety concerns. Side effect rates were generally similar between the AMX0035 and placebo groups, but the AMX0035 group did report more gastrointestinal issues (for example, diarrhea). AMX0035 also significantly decreased the rate of decline in the Revised ALS Functional Rating Scale (ALSFRS-R) compared to placebo.

Almost three years after the first participant started in CENTAUR, in July 2020, the difference in survival between the AMX0035 group and the placebo group was evaluated. People with ALS who received AMX0035 at the start of the CENTAUR trial lived an average of 6.5 months longer than the comparison placebo group.

The CENTAUR trial included an open label extension phase, where all participants who completed the placebo-controlled phase could enroll and receive AMX0035. Analysis of the data from that study showed that AMX0035 extended life by 10 months and reduced the risk of death, tracheostomy or permanent assisted ventilation, and first hospitalization.

How has The ALS Association supported the development of AMX0035?

The ALS Association committed $750,000 to Amylyx in funding for AMX0035 research and $1.4M to the NEALS clinical trial consortium to support the phase 2 trial. These grants were made possible through the ALS Ice Bucket Challenge. ALS Finding a Cure also supported this study. 

Through a standard repayment clause, the Association could recoup up to 150% of its research investment, which it will reinvest in additional research. 

The Association, in collaboration with I AM ALS, submitted a petition to the FDA in November 2020 calling on the agency and Amylyx to act swiftly and with urgency to make AMX0035 available as soon as possible. The petition was signed by more than 50,000 people from across the country who have been affected by ALS.  

Learn more here. Learn how the FDA responded here. And how The ALS Association responded back to the FDA here. 

In September of 2020, The ALS Association and I AM ALS submitted over 50,000 signatures to the FDA calling on the agency to approve AMX0035. In subsequent months, the Association held multiple meetings with FDA officials, including a public We Can’t Wait Action Meeting in May of 2021, so members of the ALS community could speak directly to FDA officials. The Association also provided scientific and regulatory guidance and in 2022, drove over 13,000 individual emails to the FDA urging approval. 

After the FDA accepted a New Drug Application for AMX0035 and convened an advisory committee to consider the effectiveness data, the Association empowered more than 13,000 people to write emails to the FDA calling for approval of the treatment.  

How Can I Access AMX0035?

To ensure every eligible person who can benefit from RELYVRIO (formerly known as AMX0035) will have access to it, Amylyx will provide support to healthcare professionals, people living with ALS, and their loved ones through the Amylyx Care Team (ACT) Support Program.

ACT provides people living with ALS who have been prescribed RELYVRIO, and their loved ones, with a dedicated, single point of contact to guide their treatment journey. ACT will aid with navigating through insurance in an effort to overcome potential barriers to access and provides financial assistance options to eligible individuals with out-of-pocket costs. People with ALS, their caregivers, and healthcare professionals in the U.S. can now call 1-866-318-2989 or email amylyxcareteam@amylyx.com to speak with an ACT team member.

Learn more about AMX0035:

Amylyx’s website: www.Amylyx.com 

Read more about the PHOENIX phase 3 trial and your eligibility to participate.