Orphan drug designation was first introduced to the European Union in 2000. The designation is granted to therapies intended to treat, diagnose, or prevent a rare, life-threatening, or chronically debilitating illness. Rare conditions, in the EU, are those affecting no more than 5 in every 10,000 people. Additionally, to achieve this status, therapies must offer benefits over existing therapies—or fill an unmet need where no therapy exists. According to SMA News Today, the European Commission recently granted Orphan Drug designation to taldefgrobep alfa for spinal muscular atrophy (SMA).
Taldefgrobep alfa is an investigational, muscle-targeted recombinant protein that could improve muscle mass and strength when used alongside other therapies. Existing treatment options can halt disease progression but cannot reverse any muscle damage or degeneration. Biohaven, the company that is currently developing this therapy, explains that it works by targeting and blocking a protein called myostatin. Typically, this protein stops muscle growth to prevent your muscles from getting too big. Biohaven hopes that, by adding taldefgrobep alfa to other treatments, it will not only stop the disease from progressing, but increase muscle mass at the same time.
Recruitment is open for a Phase 3 clinical study evaluating the safety, efficacy, and tolerability of taldefgrobep alfa for SMA. Participants can be between four and 21 years old and must currently be on treatment. Ultimately, the study aims to identify the impact of taldefgrobep alfa on improving motor skills and function.
About Spinal Muscular Atrophy (SMA)
Spinal muscular atrophy refers to a group of rare genetic disorders characterized by mild-to-severe muscle weakness and degeneration. Most SMA results from SMN1 gene mutations. These mutations cause motor neurons (nerve cells in the brain and spinal cord) to die, leading to weak and atrophied muscles.
There are multiple types of SMA, such as:
- Type 0: This is considered the rarest and most severe form of SMA. It is typically diagnosed before birth and characterized by joint contractures, weak respiratory muscles, congenital heart defects, and low muscle tone. Unfortunately, this form is often fatal in early infancy.
- Werdnig-Hoffman disease (Type I): This severe form, diagnosed at or soon after birth, is also the most common type of SMA. It is characterized by muscle weakness, developmental delays, problems with breathing and swallowing, and an inability to control head movements or sit up without assistance. A bell-shaped chest may also contribute to respiratory issues. Unfortunately, this form is often fatal in early childhood without treatment.
- Dubowitz disease (Type II): Muscle weakness in this form often manifests between ages 6-12 months. While the affected children can sit without support, they often cannot stand or walk without help. Respiratory muscle weakness, tremors, and scoliosis are symptoms of SMA type II.
- Kugelberg-Welander syndrome (Type III): SMA type III often manifests in muscle weakness in early childhood or adolescence. Standing and walking without assistance is usually achievable, but climbing stairs can be difficult. Many people utilize a wheelchair later in life.
- Type IV: This rare, late-onset form begins in early adulthood and is characterized by mild-to-moderate muscle weakness, some respiratory issues, and tremors.