Medications Currently in Trials for Schizophrenia

Medications
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@brandotron

These are the major meds in phase 2 and 3 development. There are others, like cannabidiol, and existing meds being repurposed (like Exenatide, Raloxifene, simvastatin, tocilzumab, stiltuximab) Vanderbilt/Lundbeck’s apparently unnamed drug, Reviva’s RP-5063 which seems to have stalled out, and dietary supplements like NAC and suforaphane not covered here. And there are more in phase 1, but there’s too little info to make listing those worthwhile.

Intracellular Theraputic’s Lumateperone (ITI-007)
Mechanism: 5-HT2A receptor antagonist
partial agonist of presynaptic D2 receptors and an antagonist of postsynaptic D2 receptors
serotonin transporter blocker
affinity for the D1 receptor
and lower affinity for the Alpha-1A_adrenergic_receptor and Alpha-1B_adrenergic_receptor 5-HT2C receptor and D4 receptor, indirect glutamatergic modulation
Phase: Completed phase 3, submitted to FDA for approval
What’s it for? antipsychotic
What’s so great about it?: Better, safer side effect profile. Possible benefits for disrupted sleep patterns and negative symptoms.

Minerva’s Roluperidone (MIN-101)
Mechanism: 5-HT2A and sigma-2 receptor antagonist
Phase: In the midst of phase 3, study to end about March 2020. Topline results from double-blind expected in 2019.
What’s it for?: Negative, and perhaps positive symptoms of schizophrenia
What’s so great about it?: Potentially the first medication for negative symptoms. Side effect profile looks good. Company believes it may be useful for positive symptoms as well, and may be “disease modifying.”

Newron’s Evenamide
Mechanism: glutamate modulation and voltage-gated sodium channel blockade
Phase: Company says they will begin phase 3 in the 2nd quarter of 2019 (that would be by the end of June)
What’s it for?: Add-on for the positive, negative and cognitive symptoms of schizophrenia
What’s so great about it?: No dopaminergic side effects (weight gain, sexual, cardiac, extrapyramidal). 75% of the treatment group in phase 2 responded to it. It may be useful in treatment resistant schizophrenia, or for people with an insufficient response to antispychotics.

SyneuRx’s Naben
Mechanism:: D amino acid oxidase inhibition
May increase levels of D-serine in the brain
Phase: Combined Phase2/3 scheduled for completion June 30, 2019
What’s it for?: cognition and negative symptoms
What’s so great about it?: An add-on of a well tolerated/generally recognized as safe food preservative may improve cognition and negative symptoms

Sunovion’s SEP-363856
Mechanism: 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.
Phase: Completed phase 2 and has been awarded “Breakthrough Therapy” designation by FDA.
What’s it for: Positive and negative symptoms
What’s so great about it?: Novel, non D2 mechanism. May treat negative and positive symptoms. Good safety profile.

Karuna’s KarXt
Mechanism: M1/M4 muscarinic acetylcholine receptor agonist plus a blocking agent to prevent sweating and gastro side effects.
Phase: Phase 2 expected to be completed in November 2019
What’s it for?: Preclinically (in mice) it improves positive, negative, and cognitive symptoms. Whether or not this translates to people is unknown, but it was effective on cognition in humans with Alzheimer’s. The addition of the tropsium chloride blocker could reduce or eliminate the worst side effects.

Astella Pharma’s ASP-4345
Mechanism: Undefined
Phase: Phase 2 to be completed December 2019
What’s it for?: The primary indication is for cognition. It would be an add-on to antipsychotics.

Boehringer Ingelheim’s BI 425809
Mechanism: GlyT1 inhibitor
Phase: Phase 2 to be completed February 2020
What’s it for?: Treating cognitive impairment

Takeda’s TAK-831
Mechanism: D amino acid oxidase inhibitor
Phase: Phase 2 scheduled to complete in April 2020
What’s it for?: negative symptoms and cognitive impairment

Hoffman La-Roche’s RO6889450
Mechanism: Undefined
Phase: Phase 2 scheduled to be completed July 2020
What’s it for?: Negative symptoms

Biogen’s BIIB-104
Mechanism: positive allosteric modulator (PAM) of the AMPA receptor
Phase: Phase 2 scheduled to be complted April 2020
What’s it for?: Cognitive impairment in schizophrenia

Notes:
Companies plan an end date to their trials, but often they end up getting extended.
Timelines: It typically takes 2-3 years for a phase 3 study, and the FDA 9 months to a year for review, if there were positive results. Phase 2 can take around 2 years, it can vary. There is often significant time in between the phases as the companies strategize, raise capital, analyze data, etc.

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Thank you so much! This was above and beyond what I was expecting to see!

Now if we could just get this stickied so it doesn’t get lost, I had no idea there were so many in the pipeline targeting negative symptoms and cognitive issues.

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You’re welcome. It does look substantial when it’s all typed out, doesn’t it? I know they won’t all succeed, but we’ll probably have some successes.

I think you can bookmark it. On mobile, there’s a little “…” and if you click it there’s an icon like a bookmark.

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I wonder if I can take 3 antipsychotics. I want to try these new ones but am afraid to let go of the old ones.

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Some of them, like Naben and Evenamide are being developed for adjunctive use. They have different mechanisms than 1st and 2nd gen APs. They are being tested on people who are also on APs. Looks like the ones targeting cognition will be adjunctive.

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Sticky this, allot of work went into it. Thanks for your time and effort twinkle.

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Great job.
I was tracking the prostate cancer pipeline. Put my report into a free website at sites.google.com . Then I would update the free website and link to it. Example: free pipeline website example

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Bump for @SzAdmin , this is a good summary to pin.

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I’m too scared to try new meds. Not enough long term human examples. I won’t risk it. For now.

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disease modifying? how?

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Min 101 sounds like a keeper.

Somebody bump this when it comes out. I don’t see the pinned threads. That sounds like my third AP.

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All I have seen is that they think this may be the case because of preclinical findings that it increases the expression of BDNF and GDNF.

demonstrate that administration of roluperidone significantly increased BDNF release by astrocytes and hippocampal neurons obtained from the cerebral cortex of newborn rats, as well as the release of GDNF (Glial cell derived neurotrophic factor) in cultured astrocytes. Furthermore, data showed that roluperidone enhanced BDNF gene expression at drug concentrations similar to those observed in humans at tested doses.Based on these results, researchers suggested that the effect of roluperidone on BDNF and GDNF may indicate the potential of this investigational compound for disease modification and improved neuroplasticity, in addition to its observed effects on the sigma2 and serotoninergic 5-HT2A neurotransmitter pathways.

I hope it works, it would be a major breakthrough.

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You forgot positive to is what they said

I enjoyed reading that though

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The trial on KarXt is supposed to be wrapping up. Might see news in the next several months, though it can take longer.

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New drug to add:

Takeda’s TAK-041
Mechanism: GPR139 agonist
Phase: Phase 2 scheduled to complete in Nov 2019
What’s it for?: Motivational anhedonia and cognitive impairment

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Great post sir.

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may be 4 years after phase 2 …!!

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Adding this info from Karuna. Looks like the topline results for phase 2 on positive symptoms have not yet been released. However they have planned two phase 1B trials to focus on cognition and negative symptoms.

Their phase 2 is not specifically measuring negative or cognitive symptoms, although they are measuring change in PANSS which of course includes a negative symptom scale, so we may still get some specific info.

Looks like they are splitting it this way in order to look at specific patient groups with predominantly positive, negative, or cognitive symptoms.

https://karunatx.com/the-unmet-need/

PHASE 2
Karuna is conducting a Phase 2 trial of our lead product candidate, KarXT, in schizophrenia patients experiencing acute psychosis.
Top line data is expected by the end of 2019.

PHASE 1B
A Phase 1B study of KarXT for the treatment of the cognitive symptoms of schizophrenia is expected to begin in 2020.

PHASE 1B
A Phase 1B study of KarXT for the treatment of the negative symptoms of schizophrenia is also expected to begin in 2020.

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Long way to go…!!!

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