Arimoclomol for ALS Fails to Meet Trial Endpoints

Clinical trials are extremely beneficial in learning how new and burgeoning treatment options can benefit patients. At the same time, these trials also offer insight into where treatments may not be effective – or where there is an unmet need to fulfill. According to ALS News Today, the second option is what happened within the Phase 3 ORARIALS-01 clinical trial. Altogether, the trial was evaluating the safety, efficacy, and tolerability of arimoclomol for patients with amyotrophic lateral sclerosis (ALS). Unfortunately, the trial failed to meet either the primary or secondary endpoints. Orphazyme, the drug’s developer, recently presented this data at the European Network to Cure ALS virtual meeting.


According to Orphazyme, arimoclomol is:

a first-in-class heat shock protein (HSP) amplifier:

  • A small molecule manufactured in a capsule formulation; designed to be swallowed whole, opened to allow contents to be mixed with soft foods/liquids or delivered through a nasal gastric tube or PEG
  • Designed to address neurodegenerative manifestations of disease

The investigational therapy, administered orally, helps produce more heat-shock proteins (HSPs). It can also move across the blood-brain barrier (BBB), which offers a more targeted treatment option. Normally, HSPs are able to stabilize misfolded proteins. In patients with ALS, toxic and abnormal proteins form clumps which contribute to cell damage and other health issues. Thus, researchers questioned whether arimoclomol could halt disease progression.

Altogether, 245 adult patients enrolled in the trial. All patients had experienced symptom onset within 18 months (1.5 years) of enrolling in the trial. During the trial, patients received either daily arimoclomol or a placebo for a 76-week (1.5 year) period. Researchers evaluated motor function improvement and overall survival rate as primary endpoints. However, neither of these were achieved. Additionally, secondary endpoints like task performance ability and lung function improvement also failed. While arimoclomol was relatively safe and well-tolerated, it offered no significant benefit to patients with ALS.

Outside of ALS, Orphazyme is evaluating arimoclomol as a potential treatment option for Gaucher disease, sporadic inclusion body myositis, and Niemann-Pick disease Type C.

Amyotrophic Lateral Sclerosis (ALS)

Also known as Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS) is a progressive neurological disease which is often fatal following chest muscle wasting. An estimated 5-10% of diagnoses are familial, meaning the ALS was caused by an inherited genetic mutation. However, in most cases, doctors are not sure of the exact cause of ALS; this form is called sporadic. As the disease progresses, nerve cells in the spinal cord, brain, and brain stem die. This causes muscle weakening and wasting, eventually preventing voluntary movement and control. ALS impacts males more than females. Additionally, ALS often affects those older than 60. Symptoms include:

  • Frequent tripping and falling
  • Fatigue or general malaise
  • Muscle weakness, particularly in the arms, legs, and hands
  • Unintended weight loss
  • Poor posture
  • Constipation
  • Loss of coordination
  • Shortness of breath
  • Muscle cramps and twitching
  • Depression and anxiety
  • Difficulty speaking, swallowing, performing small movements, or performing daily tasks (like walking)
  • Slurred or slowed speech
  • Inability to move muscles gradually affecting the entire body (including blinking)
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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