Fragile X syndrome

NPL-2005 and NPL-2009: Fragile X syndrome

The condition

Fragile X syndrome is the largest single cause of inherited mental retardation in the US and Europe, affecting around 1 in every 3,000 male children and 1 in 8,000 female children.

Symptoms of Fragile X syndrome include intellectual handicap, hyperactivity, attention problems, autism, emotional lability and epilepsy. There is currently no approved treatment for Fragile X syndrome.

Fragile X syndrome, which is thought to be the most common cause of inherited intellectual disability, is of considerable interest to medical, scientific and patient communities because the genetics and proteomics are fully understood. This suggests that successful treatment should be achievable.

Find out more about Fragile X syndrome in our Patients and Carers section.

The programs

Neuropharm is pursuing two separate but potentially complimentary compounds to treat the symptoms of Fragile X syndrome.

NPL-2005 is an anticonvulsant drug currently used to treat patients with Fragile X syndrome off-label, while NPL-2009, a glutamate receptor antagonist, is a targeted treatment directed at the underlying cause of symptoms.

The market

Based on the conservative estimate of 1 in every 4,000 males and 1 in every 7,000 females being sufferers of Fragile X syndrome, there is a potential US market of around 60,000 people and a potential EU market of around 90,000 people.

Our progress

NPL-2005 is an existing prescription anticonvulsant drug identified by Neuropharm and key opinion leaders.

We have completed a Phase II clinical trial in children and adolescents at a major European university hospital. The results of this open label study were presented in July 2008 at the Fragile X Foundation’s 11th International Fragile X Conference in St. Louis, Missouri. The clinical investigators conclude that data, although preliminary, suggest that NPL-2005 could be effective in the treatment of ADHD (behavioral) symptoms in young males with Fragile X syndrome. During the six months of active treatment in this pediatric population the drug was well tolerated and no treatment emergent adverse events were reported.

This was the first sponsor lead clinical study of a potential pharmaceutical treatment for Fragile X syndrome in Europe.

Neuropharm was granted Orphan Drug Designation for the use of NPL-2005 in the treatment of Fragile X syndrome in May 2008. We plan to develop NPL-2005 into an oral granule for easy administration.

NPL-2009 is a compound which has been progressed through preclinical and clinical development to Phase II trials by an international pharmaceutical company for a different medical use, before being discontinued.

Neuropharm acquired the rights to data on NPL-2009 through a collaboration in the US with the Fragile X Research Foundation (FRAXA), a patient group seeking to advance treatment of Fragile X syndrome. In conjunction with FRAXA, we have completed an exploratory Phase II trial of NPL-2009 in male and female adult patients with Fragile X syndrome. The results of this single dose, open label study which investigated the tolerability and pharmacokinetics of NPL-2009 in this patient group were published in January 2009 in the peer-reviewed Journal of Medical Genetics. The investigators conclude that the favorable safety profile and clinical effects noted in this study support implementation of further controlled trials of NPL-2009 in adults with Fragile X syndrome. In addition, the results are believed to mark the first time that the effects o a potential targeted treatment have been reported in patients with Fragile X Syndrome. We have since been working on improving the product formulation prior to additional clinical study.

Neuropharm was granted a US Orphan Drug Designation for the use of NPL-2009 in the treatment of Fragile X syndrome in November 2006.

Key points

• Neuropharm is working on two compounds which could relieve the symptoms of Fragile X syndrome: NPL-2005 and NPL-2009
• Neuropharm has completed exploratory Phase II trials for both NPL-2005 and NPL-2009 in patients with Fragile X syndrome that suggest that further clinical development work is warranted
• Neuropharm’s study with NPL-2005 was the first sponsor lead trial of pharmaceutical in Fragile X syndrome in Europe
• Neuropharm’s study with NPL-2009 was the first trial of a targeted treatment in Fragile X syndrome

Regulatory

• NPL-2005 and NPL-2009 granted Orphan Drug Status in the US

Commercialization

• We opened a US office in 2008 to build and implement plans to commercialize our neurodevelopmental compounds alone or in partnership

Market Opportunity

• There is currently no licensed treatment for Fragile X syndrome in the US or EU
• The lack of approved treatments for Fragile X syndrome represents a significant unmet medical need
• Market opportunity of approximately 60,000 sufferers in the US and 90,000 in the EU