▎WuXi AppTec Content Team Report

Today(July 5), The official website of China's National Medical Products Administration (NMPA) has recently announced that the mirogabalin besylate tablets submitted by Daiichi Sankyo have been approved for marketing.According to publicly available information from Daiichi Sankyo,Mirogabalin is a new generation calcium ion channel modulator., The indication approved this time isDiabetic Peripheral Neuropathic Pain（DPNP）。

Screenshot source:NMPA Official Website

DPNP is often referred to as "sugar pain",Refers to peripheral neuropathic pain caused by diabetes or prediabetes. Prolonged pain can severely impact the patient's normal physiological and psychological state, often leading to adverse effects such as insomnia, restricted movement, malnutrition, anxiety, and depression, significantly affecting their quality of life and work.

The mechanism of DPNP formation is complex, involving peripheral sensitization, central sensitization, dysfunction of descending inhibitory systems, and changes in ion channels, with multiple mechanisms influencing each other. After diabetes affects peripheral nerve injury, voltage-gated ion channels on the dorsal root ganglion and axonal cell membrane undergo varying degrees of change, leading to spontaneous discharge and painful neuropathy in the damaged nerves.

The voltage-gated calcium channel (VGCC) family is an important class of signal transducers on the cell surface. It is a complex protein composed of 4-5 subunits, including α1, α2δ, and β subunits. Among them, the α2δ subunit is a membrane-anchored extracellular glycoprotein that can regulate VGCC trafficking and calcium currents, and its function is associated with neuropathic pain and epilepsy. Studies have found,DPNP induces overexpression of the α2δ subunit on calcium channels (mainly presynaptic membranes) in the dorsal horn of the spinal cord, leading to abnormal opening of calcium channels, which results in hyperalgesia and allodynia. Therefore, blocking the α2δ target of calcium channels can inhibit DPNP.。

Mirogabalin is a drug developed by Daiichi Sankyo for the treatment of chronic pain. Based on in vitro studies,The drug can selectively bind to the α2δ1 and α2δ2 subunits of VGCCs. Milnacipran has a high affinity and slow dissociation for the α2δ1 subunit, and a low affinity and fast dissociation for the α2δ2 subunit.Mirogabalin was first approved for marketing in Japan in 2019 for the treatment of peripheral neuropathic pain (PNP). In March 2022, its indications were expanded to include central neuropathic pain (CNP).

Mirogabalin TreatmentDPNPThe efficacy and safety have also been validated in multiple clinical studies. In a multicenter, randomized, controlled phase 3 study, the researchers evaluated 834 cases.DPNPEfficacy and Safety of Milnacipran or Placebo in Patients Over 14 Weeks. The data shows that the dose of Milnacipran 30mg/d,The average daily pain score (ADPS) improved significantly compared to baseline, with a significantly higher proportion of patients achieving a ≥50% reduction in ADPS compared to placebo, and these patients also experienced significant improvements in sleep quality.。

In addition, a systematic review (including three randomized controlled trials, with a total of 1,732 patients with DPNP) also showed that mirogabalin had a good effect in reducing the mean daily pain score. The most common adverse reactions in the mirogabalin group were dizziness, weight gain, peripheral edema, and somnolence.

[2] Current Status of Calcium Channel Modulators in the Treatment of DPNPStatus and Progress. Retrieved Aug 31, 2023, from https://mp.weixin.qq.com/s/Y9t25uubSl-UsdCBKvZScw
[3] Daiichi Sankyo (China) submitted the marketing application for Mirogabalin Besilate Tablets, indicated for diabetic peripheral neuropathic pain.. Retrieved Jan 17，2023, from From https://mp.weixin.qq.com/s/i1uqXhTfps2d4_hx0wN9UA