Rare disease drug development can be challenging. Countries globally developed programs to incentivize innovation and development in this space. One of these initiatives is the designation of orphan drugs, or therapies used to treat rare and underserved conditions for which there’s a lack of existing or adequate treatment. In the United States, Orphan Drug designation is granted to therapies for conditions affecting fewer than 200,000 people nationwide; in the European Union (EU), this designation is granted to therapies for conditions affecting no more in 5 of every 10,000 people. Drug developers also receive numerous benefits. In the EU, Orphan Drug designation comes with fee reductions, protocol assistance, and 10 years of market exclusivity upon drug approval. Biopharmaceutical company Amylyx Pharmaceuticals recently shared that its therapy AMX0035 for Wolfram syndrome earned Orphan Drug status in the EU. (The drug previously received Orphan Drug designation in the U.S. four years ago.)
AMX0035 is an orally administered, fixed-dose combination of taurursodiol and sodium phenylbutyrate. The therapy works by targeting mitochondrial dysfunction and endoplasmic reticulum stress to prevent cell apoptosis (death) and associated neurodegenerative changes. Researchers are also exploring AMX0035 as a potential therapeutic intervention for progressive supranuclear palsy.
Orphan drug status comes following the presentation of positive interim data from the Phase 2 HELIOS clinical trial. 12 adults with Wolfram syndrome enrolled, with eight participants assessed in this interim data. After 24 weeks, the research team found that:
- Most individuals reported vision improvements.
- Wolfram syndrome did not progress in participants. Instead, disease progression and symptoms either improved or the disease was stabilized.
- Additionally, enrolled individuals saw better pancreatic function and glycemic control.
The HELIOS study remains ongoing. In addition to evaluating how safe and well-tolerated the treatment is, researchers also hope to understand how AMX0035 impacts neurological, endocrinological, and ophthalmologic function. Additional data should be available later this year.
A Deeper Dive into Wolfram Syndrome
Also known as: Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD)
The National Organization for Rare Disorders (NORD) describes Wolfram syndrome as:
an inherited condition that typically includes childhood-onset insulin-dependent diabetes mellitus and progressive optic atrophy [caused by changes in the WFS1 gene]. In addition, many people with Wolfram syndrome also develop diabetes insipidus, sensorineural hearing loss and autonomic nervous system degeneration.
Wolfram syndrome is often diagnosed in childhood or adolescence given the manifestation of symptoms. Outside of the above symptoms and characteristics, people with Wolfram syndrome may show signs of:
- Urinary tract abnormalities, such as improper bladder emptying
- Ataxia
- Poor balance
- Central sleep apnea
- Depression or anxiety
- Loss of smell
- Fatigue
- Abnormal temperature regulation (overheating)
- Autonomic dysfunction
- Constipation or diarrhea
- Dysphagia (difficulty swallowing)
- Hypogonadism
- Cataracts
- Choking
Treatment is symptomatic and supportive. There are no approved therapies for Wolfram syndrome specifically.
