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RELYVRIO™ is an FDA-approved, oral fixed-dose combination treatment for ALS in adults shown to help slow the loss of physical function1

See trial design and function and survival data below

The CENTAUR trial

The CENTAUR trial was designed in collaboration with clinical leaders, advocacy groups, and people living with ALS2-4

CENTAUR Study Design and Phases

*The OLE phase of CENTAUR included 56 participants from RELYVRIO group and 34 participants from the placebo group (n=90).
The OLE phase evaluated long-term safety and efficacy for up to 152 weeks, during which all participants were taking RELYVRIO + SOC.

The 2 Phases of the CENTAUR trial

  • CENTAUR was a multicenter study in adults with ALS that encompassed:
    • Randomized phase: A 24-week, randomized, double-blind, placebo-controlled phase (2:1 RELYVRIO to placebo)1
    • OLE phase: An open-label phase that evaluated long-term safety and efficacy for up to 152 weeks2

Abbreviation: SOC, standard of care.

Key inclusion criteria1

  • Diagnosis of definite sporadic or familial ALS per revised El Escorial criteria
  • ≤18 months since ALS symptom onset
  • Slow vital capacity >60% of predicted value
CENTAUR Clinical Trial Logo

Results were published in the 
New England Journal of Medicine
2

Key elements of the CENTAUR trial1,3

Primary efficacy end point

The primary end point of the randomized phase was a comparison of reduction rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score between RELYVRIO + SOC and placebo + SOC from baseline to 6 months.1

Baseline characteristics were generally balanced1

Balance icon representing baseline characteristics of participants being generally balanced
  • On average, participants in both arms had been diagnosed with ALS 6 months prior to baseline1
  • In both arms, the average time since onset of first ALS symptom was approximately 13.5 months1
  • The RELYVRIO arm had a higher percentage of trial participants with bulbar-onset disease vs the placebo arm (30% vs 21%, respectively)1

The majority of participants in CENTAUR were taking concomitant riluzole and/or edaravone1

77% icon representing a majority of patients treated with concomitant SOC
  • At or prior to study entry, 71% of participants were taking riluzole and 34% were taking edaravone1
  • 77% of participants took either or both of these FDA-approved ALS medications5
  • The CENTAUR trial was not designed to be a head-to-head comparison with other therapies for ALS1

RELYVRIO FUNCTION DATA (24 weeks)

RELYVRIO significantly slowed functional decline vs placebo1

MODIFIED INTENT-TO-TREAT (mITT) POPULATION (N=135):
ALSFRS-R TOTAL SCORE OVER 24 WEEKS1

Chart depicting how RELYVRIO had results as early as 6 weeks and had a 2.32-point difference at 6 months

Originally randomized to RELYVRIO + SOC (n=87)

Originally randomized to placebo + SOC (n=48)

2.32-point
difference
at the end of the 6-month
randomized phase (P=0.034)
95% CI: 0.18-4.47

 

A 2- to 3-point higher score on the ALSFRS-R may mean having a greater ability to breathe, speak, and walk, which may impact ability to live more independently.7

  • Mean ALSFRS-R total score was 2.32 points higher at week 24 compared to placebo (P=0.034)
  • As early as 6 weeks after treatment initiation, RELYVRIO showed slowing of progression1
  • Concomitant treatment with available therapies did not impact the primary outcome6

EACH POINT DECREASE ON THE ALSFRS-R REPRESENTS LOST CAPABILITY IN PERFORMING ACTIVITIES FUNDAMENTAL TO DAILY LIFE.

Comprising 12 items in 4 domains, each of these is measured on a scale of 4 to 0, with lower scores indicating less capability.

The ALSFRS-R is a validated, questionnaire-based tool for evaluating decline in physical function over time.

Bulbar function icon BULBAR Example: swallowing
Gross motor function icon GROSS MOTOR Example: climbing stairs
Fine motor function icon FINE MOTOR Example: dressing/hygiene
Respiratory function icon RESPIRATORY Example: respiratory insufficiency

Score of 4

Normal eating habits

Normal

Normal function

None

Score of 3

Early eating problems— occasional choking

Slow

Independent and complete self-care with effort or decreased efficiency

Intermittent use of bilevel positive airway pressure (BiPAP)

Score of 2

Dietary consistency changes

Mild unsteadiness or fatigue

Intermittent assistance or substitute methods

Continuous use of BiPAP during the night

Score of 1

Needs supplemental tube feeding

Needs assistance

Needs attendant for self-care

Continuous use of BiPAP during the night and day

Score of 0

NPO (exclusively parenteral or enteral feeding)

Cannot do

Total dependence

Invasive mechanical ventilation by intubation or tracheostomy

  • Mean ALSFRS-R total score was 2.32 points higher at week 24 compared to placebo (P=0.034)
  • As early as 6 weeks after treatment initiation, RELYVRIO showed slowing of progression1
  • Concomitant treatment with available therapies did not impact the primary outcome6

aThe post hoc intent-to-treat (ITT) analysis, including all 137 randomized participants, yielded results that were identical (within rounding error) to the primary mITT analysis (P=0.03).1

Abbreviation: SOC, standard of care.

RELYVRIO SURVIVAL DATA (AT UP TO 42 MONTHS FROM RANDOMIZATION)*

In a post hoc exploratory analysis, longer median overall survival was observed in participants originally randomized to RELYVRIO1

This exploratory analysis should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.1

OVERALL SURVIVAL ANALYSIS AT THE END OF THE OLE PHASE (UP TO 42 MONTHS FROM RANDOMIZATION)
ITT POPULATION (N=137)8

Chart depicting how patients on RELYVRIO had a 4.8-month longer median survival

Originally randomized to placebo + SOC (n=48)

Originally randomized to RELYVRIO + SOC (n=89)

A 4.8-month
longer median
overall survival8,a
was observed in the group originally randomized to RELYVRIO + SOC
compared to those originally
randomized to placebo + SOC
(HR, 0.644;
95% CI, 0.416-0.995)

Vital status was ascertained in 136 of 137 participants who were enrolled in CENTAUR.

Longer median overall survival was observed in the participants originally randomized to RELYVRIO + SOC compared to those originally randomized to placebo + SOC.1

*Up to 42 months from randomization; last participant, last visit in OLE phase. aMedian survival is the time at which 50% of participants have died.   Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intent to treat; NR, not reached.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Risk in Patients With Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders

RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (eg, biliary infection, active cholecystitis), severe pancreatic disorders (eg, pancreatitis), and intestinal disorders that may alter concentrations of bile acids (eg, ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions.

Use in Patients Sensitive to High Sodium Intake

RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (eg, those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately.

CONTRAINDICATIONS

None.

ADVERSE REACTIONS

The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment.

You may report side effects to FDA at 1-800-FDA-1088.

INDICATION

RELYVRIO is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults.

For more information about RELYVRIO, please see the full Prescribing Information(opens a PDF document in a new window).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Risk in Patients With Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders

RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (eg, biliary infection, active cholecystitis), severe pancreatic disorders (eg, pancreatitis), and intestinal disorders that may alter concentrations of bile acids (eg, ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions.

Use in Patients Sensitive to High Sodium Intake

RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (eg, those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately.

CONTRAINDICATIONS

None.

ADVERSE REACTIONS

The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment.

You may report side effects to FDA at 1-800-FDA-1088.

INDICATION

RELYVRIO is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults.

For more information about RELYVRIO, please see the full Prescribing Information(opens a PDF document in a new window).

References: 1. RELYVRIO. Package insert. Amylyx Pharmaceuticals Inc; 2022. 2. Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020;383(10):919-930. doi:10.1056/NEJMoa1916945 3. AMX0035 in patients with amyotrophic lateral sclerosis (ALS) (CENTAUR). ClinicalTrials.gov. Accessed December 13, 2021. https://clinicaltrials.gov/ct2/show/NCT03127514 4. Cohen, et al. Poster presented at: 2019 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference; April 13-17; Orlando, FL. 5. Paganoni S, Hendrix S, Dickson SP, et al. Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. J Neurol Neurosurg Psychiatry. 2022;93(8):871-875. doi:10.1136/jnnp-2022-329024 6. Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020;383(10)(suppl):919-930. Accessed December 13, 2021. https://www.nejm.org/doi/suppl/10.1056/NEJMoa1916945/suppl_file/nejmoa1916945_appendix.pdf 7. Cedarbaum JM, Stambler N, Malta E, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999;169(1-2):13-21. doi:10.1016/s0022-510x(99)00210-5 8. Paganoni S, Watkins C, Cawson M, et al. Survival analyses from the CENTAUR trial in amyotrophic lateral sclerosis: evaluating the impact of treatment crossover on outcomes. Muscle Nerve. 2022;66(2):136-141. doi:10.1002/mus.27569