The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to novel investigative therapy SEP-363856 for the treatment of schizophrenia.
The Sunovion and PsychoGenics psychotropic has been given an expedited pathway toward regulatory approval based on the findings of a pivotal phase 2 trial presented at the Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in December last year, as well as from a six-month, open-label, safety and tolerability extension trial.
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The therapy was found to be generally well tolerated among treated patients, with similarities to placebo in discontinuation rates, restlessness symptom rates, and changes in metabolic metrics.
What exactly does this mean? Is this significant or just another let down?
I think it’s in phase 2. But if it makes it, it could be another iti-007.
What do you mean by another iti-007?
Very low side effects. Supposedly.
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This is interesting:
SEP-363856 holds promise to be the first agent for the treatment of schizophrenia that does not bind to dopamine 2 (D2) receptors —
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“For more than 60 years, the treatment of schizophrenia has focused on blocking dopamine receptors. Finding a schizophrenia medication that works outside of a direct action on the dopamine system would be highly desirable, and SEP-363856 may represent such a breakthrough. The results of the Phase 2 trial are consistent in showing improvement in positive and negative symptoms, without the traditional side effects associated with dopamine blockers,” said Shitij Kapur, M.B.B.S, Ph.D., F.R.C.P.C., F.Med.Sci., Dean Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne. “The results need to be replicated in further studies and broader populations, but, if these results hold, it could be a remarkable advance for patients and health care providers, as well as a great new avenue for exploration of new scientific mechanisms for psychotic disorders.”
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Well, I must say that I do find this one exciting. No binding to dopamine - could this have an effect on motivation I wonder?
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It’s a race to be first, as Naben also has no binding to dopamine receptors, nor does Evenamide and they are all entering or in phase 3. However, it looks like both of those will be add-ons and SEP-363856 will be a primary med.
Oh and I’m not sure but I think MIN 101 as well. Also in phase 3.
KarXt?
Pimavanserin as well.
All of these stand to be approved in the next 2-5 years.
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This is a link about Sunovion Pharm. presentations from May 2, 2019.
It mentions it hopes for a Phase 3 trial start of SEP-363856 within the next year.
Sunovion comments May 2, 2019
“The Phase 3 program for SEP-363856 is expected to be initiated in FY2019 (April 1, 2019 – March 31, 2020).”
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I hope it works out. I like to see something that’s not a 30 day injection of a drug already on the market.
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Although the exact mechanism of action is unknown, SEP-363856 is believed to activate TAAR1 (trace amine-associated receptor 1) in addition to 5-HT1A (serotonin 1A) receptors.
it is not binding dopamine receptors but with TAAR1 receptor it alter brain dopamine… i think it have positive effect for motivation and anhedonia
Trace amines have been identified as neurotransmitters in invertebrates, and they are considered as potential neuromodulators. In particular, beta-phenylethylamine and p -tyramine have been reported to modify the release and/or the response to dopamine, norepinephrine, acetylcholine and GABA, while evidence of cross-talk between TAAR1 and other aminergic receptors has been provided.
Let’s hope so. The fact that it is still modulating dopamine through TAAR1 worries me a little bit in terms of negatives.
After four weeks, patients taking SEP-363856 showed statistically significant and clinically meaningful improvement in the Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) compared with placebo (-17.2 vs. -9.7; P=0.001, effect size = 0.45).
what does that mean? @twinklestars
-17.2 vs -9,7
x2 better than placebo?? or this numbers diffirent?
TAAR1 helps regulate dopamine, norepinephrine and serotonin transmission, and has effects in the brain’s immune system. Direct activation of dopamine and serotonin receptors, meanwhile, is believed to mediate the effects of current antipsychotic drugs, which for decades have focused on blocking dopamine receptors, the companies said.
brain’s immune system. interesting
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Yes that looks like people on the active drug had about twice the improvement in PANSS score over the time period.
Someone who knows statistics could explain the effect size better, but basically 0.45 is almost a “medium” effect size. If two groups means don’t differ by more than 0.2, the difference might not really be meaningful even though it reaches statistical significance. So the effect size is alright. It looks pretty good from those numbers.
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I really hope with all the new technology and computer science going into psychopharmacology they come out with something like clozapine without the side effects
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