Therapeutics

Masupirdine

Overview

Name: Masupirdine
Synonyms: SUVN-502
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Suven Life Sciences Ltd

Background

Developed by Suven Inc., the Delaware-based subsidiary of Indian company Suven Life Sciences, SUVN-502 is an orally available, brain-penetrant, selective antagonist of the 5-HT6 serotonin receptor (Nirogi et al., 2017). This G protein-coupled receptor is expressed mostly in the brain, where it mediates neurotransmission for functions including cognition and memory. Blocking this receptor increases cholinergic and glutamatergic signaling, and other 5-HT6 receptor antagonists have been reported to improve cognition. Several were being developed as treatments for Alzheimer's, and all were discontinued due to lack of efficacy (Upton et al., 2008IntepirdineIdalopirdineDimebon; PF-05212377).

In preclinical work, one rat study reported that masupirdine had procognitive effects, reversed age-related memory decline, increased brain acetylcholine and glutamate levels, and potentiated the effects of memantine and donepezil on brain neurotransmitters and electrical activity (Nirogi et al., 2018).

Findings

According to the company's website, Phase 1 studies were conducted in Switzerland in 2008. Suven scientists reported positive safety and pharmacokinetic data from single and multiple doses in healthy young adults and elderly volunteers (Nirogi et al., 2018).

In September 2015, a Phase 2a proof-of-concept trial began enrolling what would be 543 patients with probable Alzheimer's disease as diagnosed by the 1984 NINCDS-ADRDA criteria and an MMSE of between 12 and 20. The trial compared 26 weeks of treatment with 50 or 100 mg of SUVN-502 daily to placebo, all given in addition to donepezil and memantine. Conducted at 57 sites in the United States, this trial measured change on the ADAS-cog as primary, and change on the CDR and various clinical and functional scales as secondary outcomes. The trial missed its primary outcome, according to data presented at the 2019 CTAD (Dec 2019 conference news, slide presentation). After 26 weeks, there was no difference between groups on the ADAS-cog, nor were there changes in any secondary measures.

The company stated in a Nov 2019 press release that it would continue developing masupirdine based on subgroup analyses indicating potential benefit in some patients. Suven will provide masupirdine to eligible trial participants under an expanded access protocol, without evaluation for efficacy or safety.

For trials of this compound, see clinicaltrials.gov.

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Suven Life Sciences Ltd NCT02580305
N=537

Last Updated: 10 Jan 2020

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References

News Citations

  1. At CTAD, Early Failures and Hints of Success, from Small Trials

Therapeutics Citations

  1. Intepirdine
  2. Idalopirdine
  3. Dimebon
  4. PF-05212377

Paper Citations

  1. . Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects. Clin Drug Investig. 2018 May;38(5):401-415. PubMed.
  2. . Discovery and Development of 1-[(2-Bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole Dimesylate Monohydrate (SUVN-502): A Novel, Potent, Selective and Orally Active Serotonin 6 (5-HT6) Receptor Antagonist for Potential Treatment. J Med Chem. 2017 Mar 9;60(5):1843-1859. Epub 2017 Feb 17 PubMed.
  3. . 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease. Neurotherapeutics. 2008 Jul;5(3):458-69. PubMed.
  4. . SUVN-502, a novel, potent, pure, and orally active 5-HT6 receptor antagonist: pharmacological, behavioral, and neurochemical characterization. Behav Pharmacol. 2018 May 29; PubMed.

Other Citations

  1. I

External Citations

  1. slide presentation
  2. Nov 2019 press release
  3. clinicaltrials.gov

Further Reading

Papers

  1. . The role of 5 HT6-receptor antagonists in Alzheimer's disease: an update. Expert Opin Investig Drugs. 2018 Jun;27(6):523-533. Epub 2018 Jun 18 PubMed.