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Retrophin’s experimental PKAN drug fosmetpantotenate fails phase III trial
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease characterized by a progressive neurodegenerative disorder and buildup of iron in the brain which is estimated to affect up to 5000 patients worldwide. PKAN is inherited in an autosomal recessive manner and is caused by mutations in the PANK2 gene.
All individuals with PKAN have an abnormal buildup of iron in certain areas of the brain. A particular change, called the eye of the tiger sign seen on magnetic resonance imaging (MRI) scans of the brain.
Treatment depends on the symptoms.
There are two forms of PKAN, classical and atypical.
Classic PKAN: Symptoms of classic PKAN develop during early childhood, usually before age 10, and usually include:
- Dystonia
- Speech, chewing and swallowing problems
- Vision problems
- Intellectual disability and Psychiatric symptoms
- Speech difficulty
The first symptom is often difficulty with movement and walking and eventually lost of voluntary movements control. Muscle spasms combined with decreased bone mass can result in bone fractures. The disease may be stable for long periods of time and then undergo intervals of rapid deterioration, often lasting one to two months. Children usually lose the ability to walk by 10-15 years after the beginning of symptoms.
- Speech, chewing and swallowing problems that a feeding tube becomes necessary
- Vision problems: vision loss and night blindness.
- Intellectual disability: Cognitive functioning varies from person to person and can range from high average to below average.
Atypical form: Features of the atypical form usually progress more slowly and appear within the first three decades of life. Signs and symptoms may include:
- Speech difficulty
- Psychiatric symptoms such as behavioral problems.
- Movement problems: Loss of independent walking often occurs 15-40 years after the initial development of symptoms.
Shares dropped as much as 32% after the company announced that its investigational drug, fosmetpantotenate, did not meet the primary or secondary endpoints of the phase III study in patients with PKAN.
VB Leerink analyst Joseph Schwartz suggested that the trial had a slim change to success given that it was not based on solid data.
Developing therapeutics can be challenging due to absence of sufficient information on the Natural History of the diseases linked to the recent validated diagnosis and the small number of cases worldwide.
Many companies try to overcome the lack of natural history data with the adoption of placebo control arm study design. Unfortunately, this approach is in most of the cases not sufficient to prove a statistically significant treatment effect/s in slow progression diseases and a small number of patients enrolled in the clinical study.
Finally, we should not forget the enormous individual variability in the phenotypic clinical presentation and timing of diseases progression identified in most of these genetic and non-genetic rare diseases.
Thus, there is NOT a one-fits-all product development.
Experts should always interrogate to develop a clinical development plan that can be discussed with regulators very early in product development.
Specializing in rare disease, Boston Biotech Clinical Research works with biotech, pharmaceutical, device companies and investors to streamline the clinical trial process. Our experienced team helps each client reach their specific goals by customizing a clinical and regulatory road map of simplified programs and streamlined protocols to meet our clients’ requirements.