Effects of Roluperidone (MIN-101) on two dimensions of the negative symptoms factor score: Reduced emotional experience and reduced emotional expression

everhopeful · September 7, 2019, 10:12am

ncbi.nlm.nih.gov

Effects of Roluperidone (MIN-101) on two dimensions of the negative symptoms factor score: Reduced emotional experience and reduced emotional expression.

PD Harvey, JB Saoud, R Luthringer, S Moroz, Y Blazhevych, C Stefanescu and M Davidson, Schizophrenia research, Sep 2019 02

Recent research has suggested that negative symptoms (NS) can be considered in terms of two different dimensions: reduced expression (expressive deficit) and reduced experience (experiential deficit). Roluperidone, a compound with high affinities for 5 HT2A and sigma2 receptors, has previously shown superiority over placebo on improving NS in a prospective study in patients with schizophrenia. The objective here is to explore the effect of roluperidone compared to placebo, on the 2 domains of the Negative Symptoms.This was a multi-national Phase 2b trial that enrolled 244 symptomatically stable patients with schizophrenia who had baseline scores ≥20 on the NS subscale of the PANSS. Patients were randomized to daily monotherapy with roluperidone 32 mg, roluperidone 64 mg, or placebo in a 1:1:1 ratio. All enrolled patients were Caucasian, and 137 (56%) were male. The 3 treatment groups were balanced on all demographic and illness-related baseline characteristics.Both doses of roluperidone were superior to placebo on both domains: Reduced Experience (p ≤ .006 for the 32 mg; p ≤ .001 for the 64 mg) with persistent superiority from Week 2 for the 64 mg dose and Week 8 for the 32 mg dose; Reduced Expression (p ≤ .003 for 32 mg; p ≤ .001 for 64 mg) with similar persistence.Both doses of roluperidone previously improved PANSS negative symptoms in general and demonstrated tolerability in stable schizophrenia patients. The post hoc analysis reported here found the drug to work on both the reduced emotional experience and reduced emotional expression sub-scales empirically derived from the PANSS.

MisterCrowley · September 7, 2019, 10:15am

everhopeful:

duced expression (expressive deficit) and reduced experience (experiential deficit). Roluperidone, a compound with high affinities for 5 HT2A and sigma2 receptors, has previously shown superiority over placebo on improving NS in a prospective study in patients with schizophrenia. The objective here is to explore the effect of roluperidone compared to placebo, on the 2 domains of the Negative Symptoms.This was a multi-national Phase 2b trial that enrolled 244 symptomatically stable patients with schizophrenia who had baseline scores ≥20 on the NS subscale of the PANSS. Patients were randomized to daily monotherapy with roluperidone 32 mg, roluperidone 64 mg, or placebo in a 1:1:1 ratio. All enrolled patients were Caucasian, and 137 (56%) were male. The 3 treatment groups were balanced on all demographic and illness-related baseline characteristics.Both doses of roluperidone were superior to placebo on both domains: Reduced Experience (p ≤ .006 for the 32 mg; p ≤ .001 for the 64 mg) with persistent superiority from Week 2 for the 64 mg dose and Week 8 for the 32 mg dose; Reduced Expression (p ≤ .003 for 32 mg; p ≤ .001 for 64 mg) with similar persistence.Both doses of roluperidone previously improved PANSS negative symptoms in general and demonstrated tolerability in stable schizophrenia patients. The post hoc analysis reported here found the drug to work on both the reduced emotional experience and reduced emotional expression sub-scales empirically derived from the PANSS.

Cant wait for this drug to come out seems its going to be exceptional.

anon9805972 · September 7, 2019, 2:28pm

Anyone with access to the article: What were the adverse effects?

When is Roluperidone going to be available?

Andrey · September 7, 2019, 4:05pm

If I remember well, a drug must go through 3 successive FDA-regulated phases before it can be approved, depending on the results of each phase.
This was phase 2b for Roluperidone. So maybe in two years, if everything goes well, it can start being commercialized.

YoungSchizo · September 7, 2019, 10:23pm

These are indeed phase 2b result as a stand-alone drug for both positive and negative symptoms.

However, it’s in phase III as add-on to antipsychotics and results are delayed I guess
(to the end of 2019) because it was expected in mid 2019. The timeline before it’ll pass as an add-on and can be commercialized in US/EU is indeed within 1/2 years.

anon9805972 · September 8, 2019, 2:46am

within 1/2 years: This is so great!

twinklestars · September 8, 2019, 7:09pm

That’s very encouraging. Glad to read some good news.

saymana66 · September 14, 2019, 4:21am

Patients in the 32 mg/d group saw improvement in negative symptoms at 2 weeks, and both MIN-101 groups saw improvements at 8 weeks. Improvements were maintained throughout the trial. No notable improvement or worsening of positive symptoms occurred over the 12 weeks, and there was no significant change in body weight. Among those taking MIN-101 who reported adverse events (57.7% in the 32 mg/d group and 57.1% in the 64 mg/d group), headache (7.5%) and anxiety (6.8%) were the most common. Others included insomnia, schizophrenia symptoms, asthenia, and nausea.

revv · September 14, 2019, 6:11am

This drug doesn’t work on positive symptoms… big yikes, just another drug to feel happy

twinklestars · September 14, 2019, 9:26pm

This was tested as a monotherapy in place of a regular antipsychotic. The people involved were stable on an antipsychotic, and then switched to MIN-101 or placebo. Since the participants on MIN-101 instead of their regular med didn’t have any worsening of positive symptoms, it would appear that it does work for positive symptoms, at least as well as the other APs these folks were on.

saymana66 · September 14, 2019, 10:00pm

improvement in negative symptoms may be caused from stopping AP ?

Air · September 14, 2019, 10:36pm

Can you find any information on a possible release date? I haven’t found anything exact

twinklestars · September 15, 2019, 6:42pm

If so, then why more improvement in the active group than the placebo group?

That’s why they have placebo control blinded trials.

twinklestars · September 15, 2019, 6:50pm

There is a clinical trial (NCT03397134) underway scheduled to complete in March 2020. These almost never end on time. Apparently recruitment has been slow, and they are still recruiting so my guess is it will end sometime after March 2020.

They’ll spend some time analyzing the results and making an application to the FDA if the results were positive. The FDA will take 4 months to a year or so to approve or disapprove it, and then it usually takes awhile (months or more) to make it to pharmacies.

My guess is it could possibly be approved in 2021 if the phase 3 trial is a success - which we don’t know yet.

anon9805972 · November 29, 2019, 7:40pm

I don’t understand why recruitment has been slow. There are so many people interested in it here.

twinklestars · November 29, 2019, 11:03pm

Some news came out later that the reason recruitment was slow was because someone hacked one of their vendors.

It didn’t affect Minerva or their data but apparently it caused some problems with the recruitment website.