New data shows that SEP-363856 curtails most of the debilitating side effects linked to current schizophrenia drugs.
Justine M. Kent, MD
A major reason why patients suffering from schizophrenia do not adhere to medication is the current stable of drugs come with side effects such as weight gain and cardiovascular disease.
However, after positive results from a phase 2 study, as well as an additional 6-month open label extension, investigators from Sunovion Pharmaceuticals in collaboration with PsychoGenics believe SEP-363856 could safely treat patients with schizophrenia without the accompanying side effects.
“Essentially, what we were most impressed about when we saw the data was that this was associated with very meaningful clinical improvement over 6 months of treatment and appears to target a broad array of schizophrenia symptoms,” Justine M. Kent, MD, Head of Global Clinical Research, Psychiatry, at Sunovion, explained in an interview with HCPLive®. “In addition, what we found most interesting was what we did not see in terms of side effects.”
A total of 193 of the 245 enrolled patients completed the original 4-week study and were offered the opportunity to continue for the additional 6 months. Of these 193 patients, 166 patients continued in the open label extension, where patients were given 25-75 mg of SEP-363856.
One of the reasons for the success of the new drug is that it targets something different than what current medications target.
“The compound itself is quite novel in that it does not bind either dopamine D1 or D2 receptors and it also doesn't bind to serotonin 2A 5-HT2A receptors,” Kent said. "So, all of the currently marketed antipsychotics target either D1, D2 or both and 5HT2A.”
Rather than target those receptors, SEP-363856 influences the dopamine system in a different manner through the trace damage associated with the TAAR1 (trace amine-associated receptor 1) and 5-HT1A (serotonin 1A) receptors.
One of the main reasons for the excitement regarding the new treatment is it confers a very different side effect profile than current medications.
Typical antipsychotics feature some negative side effects that often lead to medication nonadherence, including weight gain, hyperprolactinemia, and increasing the risk of diabetes, cardiovascular disease, and tardive dyskinesia.
However, the new drug with a different molecular profile seems thus far to have a different profile in relation to those class-related side effects.
In the open-label extension, adverse events occurring in at least five percent of patients included exacerbation of schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), and anxiety (5.1%), while the effects on weight, lipids, glycemic indices, prolactin, and extrapyramidal symptoms (EPS) measures were negligible and not clinically meaningful.
According to Kent, it is particularly important to limit the side effects associated with medication because it tends to be a lifelong and chronic illness where the majority of patients diagnosed are in their late teens or early 20s.
Kent also said the side effects are usually cumulative over time, which lead to significant medical morbidity, especially for cardiovascular disorders, obesity, metabolic syndrome, and diabetes.
Along with some improvements across a broad array of symptoms, the investigators found patients taking SEP-363856 in the trial significantly improved functionally as well.
Patients treated with SEP-363856 demonstrated clinically meaningful improvements in the Positive and Negative Syndrome Scale (PANSS) total score (-22.6), the Clinical Global Impression Scale-Severity (CGI-S) score (-1.0), as well as the Brief Negative Symptom Scale (BNSS) total score (-11.3).
Sunovion recently launched the global clinical development program for the phase III study for the drug at 4 major global sites that they are currently in the enrollment stage for. Those studies are expected to be completed within 2 years.
The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for SEP-363856 for schizophrenia last May.
The investigators presented data from the 6-month extension study during the 58th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in Orlando in December.
The drug is also currently being studied in the US for Parkinson disease psychosis, with additional indications also under consideration.