Rovatirelin
An oral TRH mimic for spinocerebellar ataxia
Rovatirelin is an investigational oral drug that mimics thyrotropin-releasing hormone, the hypothalamic peptide also used in Japan as taltirelin to treat spinocerebellar degeneration. It improved ataxia in mouse and rat models, but two phase 3 trials in cerebellar ataxia found no significant benefit on their primary measure.
What is it?
Thyrotropin-releasing hormone is a three-amino-acid peptide that, beyond its role in thyroid control, acts in the brain. TRH and the TRH mimetic taltirelin are used in Japan for spinocerebellar degeneration, a group of progressive ataxias. Rovatirelin is a newer synthetic TRH mimetic designed for oral use; in rodents it activated the central noradrenergic system, improved motor function in the rolling mouse Nagoya model of hereditary ataxia, and ameliorated gait problems in a rat model of sporadic ataxia.
Two phase 3 trials then tested it in patients with cerebellar ataxia. KPS1301 randomised 374 patients to 1.6 mg, 2.4 mg or placebo; KPS1305 randomised 203 to 2.4 mg or placebo, over 24 to 28 weeks. Neither showed a significant difference in the primary endpoint, change in the Scale for the Assessment and Rating of Ataxia. A pooled analysis of patients meeting the second trial's criteria found a small difference favouring the 2.4 mg dose.
In a human mass-balance study, it was steadily absorbed with peak levels 5 to 6 hours after an oral dose, circulating with a major metabolite. It is not approved.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
Studies of rovatirelin, from their PubMed abstracts.
Two phase 3 trials in cerebellar ataxia
In KPS1301 (374 randomised) and KPS1305 (203), rovatirelin did not differ significantly from placebo on change in SARA score; a pooled analysis of 278 patients favoured 2.4 mg slightly.
Human mass balance
After a single oral dose in healthy men, rovatirelin was steadily absorbed with peak plasma levels at 5-6 hours, and it and its metabolite TAMP were the main circulating components.
Hereditary ataxia mice
Rovatirelin dose-dependently improved motor function in the rolling mouse Nagoya model of hereditary ataxia and was compared with taltirelin.
Sporadic ataxia rats
Oral rovatirelin ameliorated motor dysfunction in a cytosine arabinoside-induced rat model of sporadic spinocerebellar degeneration.
Central noradrenergic effects
Rovatirelin, a synthetic TRH mimetic, acted on the central noradrenergic system, and its effects were compared with taltirelin, which is approved for spinocerebellar degeneration in Japan.
Interaction with itraconazole
In 16 healthy subjects, the CYP3A4/5 and P-glycoprotein inhibitor itraconazole raised rovatirelin's peak concentration 3.05-fold and exposure 2.82-fold, while lowering its metabolite TAMP.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
No label; it is investigational.
Legal Status
Rovatirelin is investigational.
Frequently Asked Questions
?What is rovatirelin?
An investigational oral drug that mimics thyrotropin-releasing hormone, developed for spinocerebellar ataxia.
?Did rovatirelin work in ataxia?
Not on the main measure: two phase 3 trials found no significant difference from placebo, though a pooled analysis slightly favoured the higher dose.
?How is it related to taltirelin?
Both are TRH mimetics. Taltirelin is approved in Japan for spinocerebellar degeneration; rovatirelin was developed as a newer oral alternative but has not been approved.
?How long were the phase 3 trials?
KPS1301 treated patients for 28 weeks and KPS1305 for 24 weeks, each followed by 4 weeks of follow-up, with change in the Scale for the Assessment and Rating of Ataxia as the primary endpoint.
?How is rovatirelin handled by the body?
In healthy men given a single radiolabelled oral dose, it was steadily absorbed, peaking at 5 to 6 hours, and circulated with its metabolite TAMP; total radioactivity exposure was about five times that of the parent drug.
?Is rovatirelin available anywhere?
No. It has not been approved, so it is not available outside clinical trials.
?Does rovatirelin interact with other drugs?
Yes. In a study in healthy volunteers, itraconazole, which blocks the enzyme CYP3A4/5 and the transporter P-glycoprotein, nearly tripled rovatirelin's blood levels.
References
- [clinical-trial] Nishizawa M, et al. "Effect of rovatirelin in patients with cerebellar ataxia: two randomised double-blind placebo-controlled phase 3 trials." J Neurol Neurosurg Psychiatry, 2020;91(3):254-262. PMID: 31937586.
- [pubmed] Kobayshi K, et al. "Human mass balance, pharmacokinetics and metabolism of rovatirelin and identification of its metabolic enzymes in vitro." Xenobiotica, 2019;49(12):1434-1446. PMID: 30747023.
- [pubmed] Ijiro T, et al. "Ameliorating effect of rovatirelin on the ataxia in rolling mouse Nagoya." Eur J Pharmacol, 2020;882:173271. PMID: 32534077.
- [pubmed] Ijiro T, et al. "Rovatirelin ameliorates motor dysfunction in the cytosine arabinoside-induced rat model of spinocerebellar degeneration via acetylcholine and dopamine neurotransmission." Clin Exp Pharmacol Physiol, 2022;49(9):950-958. PMID: 35637550.
- [pubmed] Ijiro T, et al. "Effect of rovatirelin, a novel thyrotropin-releasing hormone analog, on the central noradrenergic system." Eur J Pharmacol, 2015;761:413-22. PMID: 26142830.
- [clinical-trial] Kobayashi K, et al. "Pharmacokinetic Drug Interactions of an Orally Available TRH Analog (Rovatirelin) With a CYP3A4/5 and P-Glycoprotein Inhibitor (Itraconazole)." J Clin Pharmacol, 2020;60(10):1314-1323. PMID: 32459872.
Sources & Citations
Studies were read from their PubMed records, October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.