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.”
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.
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
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.
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
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
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
Phase: Phase 2 scheduled to be completed July 2020
What’s it for?: Negative symptoms
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
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.