NPL-2008: Autism
The condition
Autism Spectrum Disorders affect 1 in 110 children in the US,
according to the US
Center for Disease Control.
It is a complex neurological disorder that typically impacts the
development of children, persists into adult life, and embraces a
range of conditions of varying degrees of severity.
Find out more about autism in our Patients and Carers section.
The program
NPL-2008 is based on the generic compound fluoxetine, a
selective serotonin reuptake inhibitor (SSRI) designed to increase
serotonin levels in the brain.
Our rationale is that fluoxetine is able to address the low levels
of serotonin observed in patients with autism, increasing brain
activity and decreasing repetitive behavior. This has been backed
by peer-reviewed academic research and off-label prescribing of
fluoxetine.
The market
It is estimated that there are more than 1.8 million cases of
Autism Spectrum Disorders in the US and around 2.8 million
cases in the EU. There is currently no approved drug for a core
symptom of autism in the US.
Our market research in the US shows us that clinicians believe that
up to 65% of patients would benefit from SSRI therapy.
There has been a positive reaction from key opinion leaders, child
and adolescent psychiatrists and pediatric neurologists regarding
the potential of NPL-2008 in treating autism.
Our progress
In 2006 Neuropharm acquired the rights to the NPL-2008 program from the Mount Sinai School of Medicine in New York, where Professor Eric Hollander was granted Orphan Drug Designation (ODD) in 1999 for the use of fluoxetine in autism.
Orphan drug status would allow seven years marketing exclusivity
for fluoxetine in autism and is key to the commercial viability of
NPL-2008.
Professor Hollander has already completed a series of clinical
trials of fluoxetine in children and adults in work funded by the
Food & Drug Administration’s Office of Orphan Product
Development.
In February 2007, Neuropharm formed an agreement with Catalent
Pharma Solutions under which fluoxetine will be delivered through
their patented Zydis® tablet. Zydis® is the fastest orally
dissolving tablet in the world and designed to enhance compliance
in both children and adults.
Catalent developed NPL-2008 in three dosage strengths in
preparation for Neuropharm’s SOFIA (Study of Fluoxetine in Autism)
trial at 19 centers of excellence in the US, the study was carried
out in collaboration with the US patient organization Autism
Speaks. FDA granted Special Protocol Assessment for SOFIA, as well
as granting Fast Track Status in April 2008. Neuropharm commenced a
Rolling NDA submission in September 2008, which is still
ongoing.
In February 2009, Neuropharm announced the completion of the Phase
III SOFIA study. The novel Zydis® formulation of fluoxetine was
generally well tolerated by patients and no serious adverse events
were reported. However, in this low-dose study the primary
endpoint, which was a reduction in the measurement of repetitive
behaviors at the end of treatment, was not achieved. The SOFIA
study showed that repetitive behaviors were reduced after both
NPL-2008 and placebo treatment; a statistically significant
difference between the two groups was not demonstrated.
Neuropharm has completed a detailed analysis and review of the SOFIA data to gain a better understanding of the results. This analysis has led us to conclude that NPL-2008 merits further study in the treatment of Autistic Disorder and that the compound retains the potential to be the world’s first licensed therapy for a core symptom of Autism. After lengthy discussion with experts in the field, we believe that an improved trial design with the inclusion of different dose titration options will be necessary to fully demonstrate the effectiveness of this compound.
Key points
- Over 10 years’ work on the program by Professor Eric Hollander, now a consultant to Neuropharm
- The FDA Office of Orphan Drug Development has funded two clinical trials, showing a continued involvement with the program
- US Orphan Drug Status allows seven years marketing exclusivity upon approval
- Collaboration with Catalent for customized, low dose, fast melt Zydis® formulation
- 20 compounds have already been successfully formulated and marketed in Zydis®
- Formulation and manufacturing program is on track
Market opportunity
- Over 1.8 million US patients and 2.8 million patients in the EU with Autism Spectrum Disorders