sodium phenylbutyrate + taurursodiol

The drug sodium phenylbutyrate + taurursodiol (also known as PB-TURSO or AMX0035) is a combination medication used to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. It consists of 3 grams of sodium phenylbutyrate and 1 gram of taurursodiol (also called ursodoxicoltaurine) per dose[1][2][8]. ## Approval and Development Status The FDA approved this combination in September 2022 under the brand name Relyvrio, following priority review and orphan drug designations[2][4]. It received conditional approval in Canada in June 2022 under the brand name Albrioza[2][3]. The approval was based on the Phase 2 CENTAUR clinical trial, which demonstrated slower functional decline in ALS patients compared to placebo[4][5]. However, in March 2024, Amylyx Pharmaceuticals announced that their Phase 3 PHOENIX trial showed no statistically significant difference between Relyvrio and placebo in ALS patients[2]. This larger trial involved 664 American and European adults followed over 48 weeks. ## Mechanism of Action While the exact mechanism isn't fully understood, researchers believe sodium phenylbutyrate + taurursodiol works by: 1. Preventing neuronal death in ALS patients 2. Sodium phenylbutyrate appears to reduce endoplasmic reticulum stress 3. Taurursodiol (ursodoxicoltaurine) improves mitochondrial energy production[2][8] Together, these mechanisms may help slow the progression of ALS by protecting neurons from damage and death. ## Dosage and Administration The medication comes as a powder in single-dose packets that must be mixed with water before taking. The typical dosing regimen is: - Initial: 1 packet daily for the first 3 weeks - Maintenance: 1 packet twice daily thereafter[1][6][9] Each packet contains 3 grams of sodium phenylbutyrate and 1 gram of taurursodiol. The mixture should be taken within 1 hour after mixing, preferably before a meal or snack. It can be administered orally or through a feeding tube[1][6]. ## Side Effects The most common adverse effects are gastrointestinal, including: - Diarrhea - Abdominal pain - Nausea - Bitter taste in the mouth after administration[8][9] ## Cost and Accessibility As of 2023, AMX0035 costs approximately $158,000 annually in the US, which may present a financial barrier for many ALS patients[3]. ## Clinical Evidence The CENTAUR trial demonstrated that sodium phenylbutyrate + taurursodiol slowed functional decline in ALS patients as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The mean rate of change in ALSFRS-R score was -1.24 points per month with the active drug versus -1.66 points per month with placebo, representing a significant difference[5][7]. Follow-up data showed that patients who received the drug had longer survival times, with median key event-free survival being 4.8 months longer and median tracheostomy/permanent airway ventilation-free survival being 7.3 months longer compared to placebo[4].

Brand names

RelyvrioAlbrioza

Other names

sodium phenylbutyrate and taurursodiolPB-TUDCAAMX0035AMX-0035AMX 0035