Piromelatine

Neurim Pharmaceuticals has developed and globally patented Piromelatine, a New Chemical Entity.

Piromelatine is a melatonin MT1/2/3 and serotonin 5-HT-1A/1D receptors agonist developed for Sleep disorders and Alzheimer’s Disease.

Piromelatine in insomnia patients

Piromelatine, a novel investigational multimodal sleep medicine is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine is thought to work through a combination of MT1\MT2 (sleep promoting effects, neuroprotective effects) and 5HT1A\D (antidepressant and anxiolytic effects) receptors agonism.

All potential effects of Piromelatine were demonstrated in relevant rodent models of central sensitivity syndrome and sleep maintenance (Liu et al 2014), pain (Chen et al 2014), neuroprotection and cardioprotection (He et al 2013, Yu et al 2014), diabetes (She et al 2009, She et al 2014, Wang et al 2013, Li et al 2013), hypertension (Huang et al 2013), neurodegenerative diseases (He et al 2013), anxiety and depression (Tian et al 2010).

Neurim completed a Phase II clinical trial for this multi-targeted drug candidate that has already demonstrated efficacy and safety in patients aged 18–80 with primary insomnia. In this study, Piromelatine demonstrated a good potential for the treatment of insomnia characterized by sleep maintenance disturbances. Additionally, Piromelatine was found to preserve REM sleep and induce deeper sleep with less arousal. Piromelatine was generally safe and well tolerated, with no detrimental effects on next-day psychomotor performance.

Piromelatine in Alzheimer’s Disease patients

In preclinical studies in cell and animal models of Alzheimer’s Disease Piromelatine was found to protect from neural damage, facilitate memory performance and improve cognitive impairment (He et al 2013) and attenuate Alzheimer’s disease risk factors such as insulin resistance (She et al 2009, She et al 2014, Wang et al 2013, Li et al 2013), hypertension (Huang et al 2013, Yu et al 2014) and sleep disorders (Liu et al 2014).

Neurim has already completed a Phase II study with Piromelatine for insomnia, in which the drug has demonstrated dose dependent efficacy in improving sleep maintenance and a good safety profile. Based on its mechanism of action and the preclinical and clinical data generated so far, and the recent discovery of causal relationship between sleep and Alzheimer’s Disease incidence and progression, the company is initiating a Phase IIB study on the efficacy and safety of Piromelatine in patients with mild Alzheimer’s Disease.

Piromelatine is expected improve sleep, circadian rhythms control and subsequently cognition in the patients through its action at MT receptors, improve memory and mood enhance slow wave sleep and reduce wakefulness during the night through its 5-HT1A activity and increase neurogenesis through the synergistic activation of melatonergic and 5-HT1A receptors. Piromelatine’s novel multi-targeted mechanism of action represents a new thinking on Alzheimer’s Disease pathogenesis and holds potential breakthrough benefits in sleep disorders and Alzheimer’s Disease.

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