Mirogabalin expands treatment option for Asians with peripheral neuropathic pain

Mirogabalin besylate appears to provide an early analgesic effect in Asian patients with peripheral neuropathic pain (PNP) with a tolerable safety profile, according to a pooled analysis of two phase III studies.

Pain relief occurred within 2 days of treatment initiation, with the effect intensifying as the daily dose of mirogabalin increased, the investigators said. “Most treatment-emergent adverse events (TEAEs) were mild or moderate, and many patients could continue treatment without interruption or discontinuation during the study period.”

A novel, selective ligand of the α2δ subunit of voltage-gated calcium (Ca2+) channels, mirogabalin has exhibited potent and long-lasting analgesic effects in rat models of neuropathic pain and fibromyalgia. Other α2δ ligands, such as gabapentin and pregabalin—drugs used to prevent seizures—are used off-label to relieve their pain. [J Pain Palliat Care Pharmacother 2013;27:268-283; Pain Med 2015;16:2075-2083]

“However, the optimal dosing of α2δ ligands has been limited by AEs, most of which affect the central nervous system. Common AEs observed in association with α2δ ligands include fatigue, dizziness, sedation, somnolence, ataxia, peripheral oedema, and increased weight,” the investigators noted. [Expert Rev Neurother 2016;16:1263-1277]

In the current study, the investigators synthesized data from the two pivotal phase III studies of mirogabalin in Asian patients with the aim of gaining a deeper insight into the safety of mirogabalin for PNP and to present clinicians with more detailed information regarding the use of the selective α2δ ligand across the spectrum of diabetic (D)PNP and postherpetic neuralgia (PHN) patients, including the elderly and those with other comorbidities. [J Diabetes Investig 2019;10:1299-1306; Pain 2019;160:1175-1185]

Conducted at multiple sites in Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand, the two studies were almost identical. A total of 1,587 patients (824 with DPNP; 763 with PHN) with baseline average daily pain score (ADPS) of <6 or ≥6 had been randomly assigned to placebo (n=633), mirogabalin 15-mg once daily (QD; n=316), mirogabalin 10-mg twice daily (BID; n=318), or mirogabalin 15-mg BID (n=320) treatment groups.

The most common TEAEs were somnolence (3.8 percent, 10.8 percent, 14.5 percent, and 19.1 percent, respectively) and dizziness (2.7 percent, 5.7 percent, 9.1 percent, and 13.1 percent). Drowsiness led to treatment discontinuation in two patients (0.6 percent) given mirogabalin 15 mg QD, while both dizziness and somnolence ended in withdrawal in six (1.9 percent) and three (0.9 percent) patients in the mirogabalin 15-mg BID group, respectively. In the mirogabalin 10-mg BID group, somnolence, oedema, and peripheral oedema each resulted in three (0.9 percent) treatment cessation.  [Clin Ther 2021;doi:10.1016/j.clinthera.2021.03.015]

At week 14, ADPS significantly decreased on mirogabalin 10 mg BID and 15 mg BID vs placebo (least squares mean changes, −0.31 and −0.63, respectively). Of note, the analgesic effect of the two dosing schedules was evident after only 2 days.

“Subgroup analysis also showed that aside from baseline ADPS, no other factors influenced the efficacy of mirogabalin to a notable extent. Thus, [the] findings … suggest that the effects of mirogabalin might be consistent across most subpopulations defined according to demographic and baseline features,” according to the investigators.

While female sex, age ≥65 years, and baseline weight <60 kg may influence the safety of mirogabalin, specifically the incidence of somnolence and dizziness, these factors had no notable impact on efficacy, the investigators added.

“Considering the pathophysiology of PNP and the analgesic mechanism of action of mirogabalin … [the drug] is expected to be an important new treatment option for many patients with PNP,” they pointed out.

Mirogabalin is approved to treat PNP in several countries, and current Japanese guidelines recommend the selective α2δ ligand as a first-line treatment option. [Drugs 2019;79:463-468; https://minds.jcqhc.or.jp/english/english_guideline/G0000989]