Phase 3 SIDEROS Trial for DMD Drug Idebenone Fails

While many pharmaceutical companies submit approval and marketing applications, not all are successful. According to Fierce Biotech, a subsidiary of Questex, Santhera Pharmaceuticals (“Santhera”), is one of the most recent companies to experience this failure. Following a failed interim analysis, Santhera halted their Phase 3 SIDEROS clinical trial. Ultimately, the trial was designed to support the potential approval of idebenone for patients with Duchenne muscular dystrophy (DMD).


According to DrugBank, idebenone is a small molecule:

[small molecule] synthetic analogue of ubiquinone, a vital cell antioxidant and essential component of the Electron Transport Chain (ETC). It has been proposed that by interacting with the ETC, idebenone increases ATP production required for mitochondrial function, reduces free radicals, inhibits lipid peroxidation, and consequently protects the lipid membrane and mitochondria from oxidative damage.

Outside of DMD, idebenone has been tested as a treatment for Alzheimer’s disease (unsuccessfully). However, it is EMA-approved for the treatment of patients with Leber’s hereditary optic neuropathy (LHON).

The journey for idebenone’s EMA approval for the treatment of DMD has been long and drawn out. In 2017, the EMA rejected the drug application. An appeal in 2018 was also unsuccessful. Next, Santhera filed for approval again in 2019 using data which showed how the drug prevented or slowed respiratory damage.

Santhera then began the Phase 3 SIDEROS trial. Ultimately, the plan was to use this data to file a separate drug application in the United States. 255 patients enrolled in the trial. Patients received either idebenone or a placebo. However, the results (not yet shared) were disappointing. Because the drug failed the interim analysis, Santhera ended the clinical trial. Now, as the global development program officially ends, Santhera must restructure the business. Their new focuses will be developing lonodelestat for cystic fibrosis (CF) and vamorolone for DMD.

Duchenne Muscular Dystrophy (DMD)

Inherited in an X-linked recessive pattern, Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy, a condition causing progressive muscle loss and weakness. Patients with DMD cannot make enough dystrophin in their muscles. Generally, DMD affects males significantly more frequently than females. Around 1 in 3500 male births and 1 in 50 million female births have DMD. Symptom onset usually occurs before age 6. Symptoms include:

  • Frequent falling
  • Fatigue
  • Muscle weakness which begins in the lower extremities
  • Poor motor function
  • Intellectual and developmental delays
  • Difficulty walking or changing positions
  • Heart disease (later stages)
  • Respiratory failure (later stages)

Learn more about DMD.

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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