Retrophin, Inc. has signed an agreement with Novartis Pharma AG for an exclusive US license for Syntocinon nasal spray, the intranasal formulation of a synthetic version of the naturally occurring peptide hormone oxytocin, for an upfront payment of $5.0 million plus milestone payments and royalties.

Syntocinon nasal spray was approved in the US in 1960 to assist initial postpartum milk ejection, but was discontinued by Novartis in 1997 for commercial reasons. Retrophin plans to reintroduce the product for prescription use in the US in Q2 2014. Additionally, the company intends to pursue a clinical trial program with Syntocinon for its potential use as a treatment for schizophrenia and autism.

Difficulty breastfeeding newborn infants is an unmet medical need. There is no FDA-approved drug currently available in the US for this patient population. In a Retrophin-conducted survey of 50 obstetricians, respondents indicated that 16 per cent of new mothers in their care have problems with milk let-down, and 79 per cent of these physicians said they would use Syntocinon if it became available for this indication.

One per cent of Americans suffer from schizophrenia according to National Institute of Mental Health estimates. Over the past four years, three randomized, double-blind, placebo-controlled, independent proof-of-concept schizophrenia trials were conducted in patients whose symptoms were inadequately controlled despite receiving therapeutic doses of an atypical antipsychotic123. All three studies suggest that intranasal oxytocin administered as an adjunct to subjects' antipsychotic drugs improves positive and negative symptoms, as assessed by the Positive and Negative Syndrome Scale (PANSS), significantly more than placebo.

Preclinical evidence indicates that oxytocin has a critical role in the regulation of brain-mediated processes that are strongly relevant to many neuropsychiatric disorders. Small studies suggest that even a single dose of intranasally delivered oxytocin can have significant, pro-social effects on human behavior. Finally, there have been several positive findings with oxytocin in animal models of schizophrenia.

Commenting on today's news, Martin Shkreli, founder and chief executive officer of Retrophin, noted, "We believe the reintroduction of intranasal Syntocinon for lactation deficiency would be a welcome option for obstetricians and their patients, while providing Retrophin with a revenue stream. Equally important, we believe that Syntocinon is an underutilized drug. Compelling data from studies that show positive results in patients with schizophrenia and autism lead us to believe that this drug may have significant utility in treating these conditions. We look forward to initiating a clinical programme in order to develop the drug for these indications."

Clinical studies also suggest that oxytocin may have positive effects in patients with autism spectrum disorders. Studies have shown that the administration of oxytocin improves mental representations of self, social cognition, and quality of life in patients with autism. Evidence suggests that, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism. Large, controlled studies are warranted to confirm these findings.

In a recent article discussing oxytocin as a potential therapeutic target for schizophrenia and other neuropsychiatric conditions, Dr David Feifel (Department of Psychiatry, University of California, San Diego, San Diego, CA) stated that if preliminary results are confirmed in larger trials, "..it may signal the beginning of an exciting new era in the treatment of schizophrenia and perhaps other neuropsychiatric disorders, something desperately needed given the disappointing lack of progress in developing efficacious novel mechanism treatments in this field."

Retrophin is a pharmaceutical company focused on the development, acquisition and commercialization of drugs for the treatment of serious, catastrophic or rare diseases for which there are currently no viable options for patients.