Ulotaront (SEP-363856) Effective for Negative Symptoms


The long-term study of ulotaront has an estimated primary completion date of November 2022…


This is an old article right. There’s 2 clinical trials that’s supposed to be completed recently but I can’t seem to find the results

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I’m not sure about other trials, I’m waiting for November 2022… :slight_smile:

There’s 2 phase iii completed in October and November 2021 but results not announced yet

This was published on the 9/12/21, so today…

Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study | npj Schizophrenia (nature.com)

“Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25–75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront.”


What does that mean?

“PANSS total score of −22.6 (−25.6, −19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of −1.0 (−1.2, −0.8; effect size, 1.07)”


Ulotaront is the new name for Sep 3…

Positive and negative symptoms reduction by points on a scale the docs use. The reduction is a good thing, I am led to believe.

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Is it better than current APs for negative symptoms?

I don’t know what the PANsS scores are for the other aps.

This is the game changer they reckon for new aps. It is supposed to be good for negative symptoms too.


Ulotaront Effective for Negative Symptoms in Patients With Acute Schizophrenia - Psychiatry Advisor

“Ulotaront was found to result in significantly greater improvement in negative symptoms on the Brief Negative Symptom Scale (BNSS) total score (ES 0.48) and factor scores, the MARDER Positive and Negative Syndrome Scale (PANSS) negative symptom factor (ES 0.46), and the Uncorrelated PANSS Score Matrix negative deficit of expression (UPSM-NDE, ES 0.32) and Uncorrelated PANSS Score Matrix negative-apathy/avolition (UPSM-NAA ES 0.32) factors.”


Good news for you, isn’t it? Got a few years to wait for it though.


That’s a nice big effect size for the PANSS total score.

Not as big for the negative symptom scale BNSS, but still respectable. (effect size 0.48) This is a medium effect size.

Effect size deals with the magnitude of the effect between groups. A treatment could be statisically significant without being meaningful. This looks like a meaningful, and not just statistically significant, difference.


Looking at the publication that came out today, the 26 week open label extension. I think it looks really good. I hope that they will replicate this in a longer placebo controlled trial.

Mean change from double-blind baseline to open-label baseline in PANSS total score was −22.6; and mean changes from double-blind baseline to open-label weeks 4, 12, 20 and 26 were −34.1, −36.3, −37.4, and −42.4, respectively.

42 points down on PANSS is big. Although this group of patients had experienced an acute exacerbation and probably had a high starting PANSS - I don’t know what the average was.

They talk a little bit about the response rates. That’s important because we want to know did the drug benefit most of the people or just a subset? It looks like it benefited most people.

Treatment response rates (≥30% reduction in PANSS total score from double-blind baseline) for double-blind ulotaront and double-blind placebo patients, respectively, were 94.1% and 92.5% at week 26

a 30% reduction in ~95% of people is pretty damn good.

They also found a ≥50% decrease in PANSS in about two thirds of patients. That’s even better.

response rates (≥50% reduction in PANSS) were 76.5% and 67.9% at week 26

There were no significant changes in body weight, cholesterol, glucose, or prolactin.

Up to 26 weeks of open-label treatment with ulotaront was associated with minimal changes in body weight (mean observed change from double-blind baseline to week 26, −0.3 kg)

No noteworthy changes were observed in metabolic laboratory parameters, including total cholesterol (median change from double-blind baseline to week 26, −2.0 mg/dL), triglycerides (−5.0 mg/dL), glucose (+2.0 mg/dL), or HbA1c (0.0%; Table 4). Treatment with ulotaront had no clinically meaningful effect on serum prolactin levels in either female (median change at week 26, −3.4 ng/mL) or males (−2.7 ng/mL

No patient had a QTcF interval ≥480 msec at any time point during the 26-week extension phase

In the open label study (everyone on the active drug) adverse events reported were:

schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), and anxiety (5.1%)

Since everyone was on the drug, I don’t know how helpful this is in terms of whether or not these were caused by the drug. But low incidences anyway.

A small improvement in sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) global score, was observed at week 26 (mean [SD] change from open-label baseline −2.0 [3.0]).

Movement disorder scales showed no clinically meaningful changes from open-label baseline to week 26 (observed case): mean (SD) changes in the Simpson–Angus Scale (SAS) mean score, Barnes Rating Scale for Drug-Induced Akathisia (BARS) total score, and the Abnormal Involuntary Movement Scale (AIMS) total score were −0.0 (0.1), −0.1 (0.2), and 0.0 (0.1), respectively.

Overall, looks very promising.


There are still five Phase 3 clinical trials recruiting, one of which is in Japan.
5 trials recruiting


Does anyone know what year can we expect this medication?

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The study is conducted ages ago, it’s a repost

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2023 scheduled to release in usa and probably some parts of EU can ship it over, later half of 2020 to be released in asia

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2023 on market in the USA, I don’t know about other countries.

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I’m getting mixed results from people who say the medication is no better than current APs and people like you who say it’s the opposite. What is the difference between PANSS and BNSS. There are litterally no reviews from people about this medication online. I’m really interested in it possibly working for just generally anhedonic people. Who knows but we need more info on this drug for sure

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