Name: RVT-101
Synonyms: SB-742457 , GSK 742457
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease, Dementia
U.S. FDA Status: Alzheimer's Disease (Phase 2), Dementia (Phase 2)
Company: Axovant Sciences Ltd.


Originally developed by GSK under the name SB-742457, RVT-101 is an antagonist of the serotonin receptor 6 (5-HT)6, a largely CNS-specific member of the serotonin receptor subfamily. The serotonergic neurotransmitter system is impaired as Alzheimer’s develops and progresses, and modulating it is seen as a potential therapeutic avenue (Upton et al., 2008). SB-742457 has been reported to reverse both experimentally induced and age-related learning deficits in rats (de Bruin et al., 2013Callaghan et al., 2012). This drug does not target central AD pathways of Aβ amyloidosis and tauopathy; rather, it represents an approach to enhancing cognition in Alzheimer's and other forms of dementia (Codony et al., 2011).


Several Phase 1 studies compared SB-742457 in capsule and tablet formulations, and showed that the compound was well-tolerated.

GSK completed four Phase 2 studies of this compound, all in patients with mild to moderate AD. Between 2005 and 2007, a six-month dose-ranging trial of SB-742457 monotherapy measured the effect that 5 mg, 15 mg, or 35 mg of the drug taken once daily had on cognition (ADAS-Cog) and global clinical function (Change plus Caregiver Input, CIBIC-plus) in 371 patients in the European Union, Croatia, Russia, South Africa, Chile, South Korea, and New Zealand. That trial reported a small but dose-dependent benefit of the study drug on both measures, as well as acceptable tolerability (Maher-Edwards et al., 2011; August 2008 conference news).

In December 2014, Axovant Sciences acquired rights to this drug and renamed it RVT-101. At AAIC 2015, Axovant presented a completer analysis of prior phase 2b GSK data that had previously been analyzed based on the intent-to-treat population, and came up with a slightly larger effect size on essentially similar efficacy results. According to Axovant, a Phase 3 program for mild to moderate AD, as well as trials in other forms of dementia, is in planning (see company press release). On Oct 6, 2015, the company announced that it had begun screening for a trial of a once-daily dose of 35 mg RVT-101 added to stable donepezil therapy in 1,150 patients with mild to moderate AD. Set to run until October 2017, this registration trial aims to confirm the prior GSK study, with a standard co-primary outcome of ADAS-cog and ADCS-ADL. A 12-month open-label extension is also being offered. For trials of this compound, see clinical and clinical

At the 2015 CTAD conference, Axovant presented a poster claiming nearly full recptor occupancy at the dose used in phase 3. Axovant also announced plans to evaluate this drug in dementia with Lewy bodies (DLB). 


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News Citations

  1. Chicago: More News From Phase 2s

Paper Citations

  1. . SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study. Int J Geriatr Psychiatry. 2011 May;26(5):536-44. PubMed.
  2. . 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease. Neurotherapeutics. 2008 Jul;5(3):458-69. PubMed.
  3. . Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP-induced deficits in reversal learning in the two-lever operant task in male Sprague Dawley rats. Behav Brain Res. 2013 May 1;244:15-28. Epub 2013 Feb 4 PubMed.
  4. . Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457. Neuropharmacology. 2012 Oct;63(5):890-7. Epub 2012 Jul 2 PubMed.
  5. . 5-HT(6) receptor and cognition. Curr Opin Pharmacol. 2011 Feb;11(1):94-100. Epub 2011 Feb 15 PubMed.

External Citations

  1. company press release
  2. clinical
  3. clinical

Further Reading


  1. . 5-HT(6) receptor and cognition. Curr Opin Pharmacol. 2011 Feb;11(1):94-100. Epub 2011 Feb 15 PubMed.
  2. . 5-HT6 receptor antagonists as potential therapeutics for cognitive impairment. Curr Top Med Chem. 2010;10(2):207-21. PubMed.