Dersimelagon (MT-7117)

Dersimelagon is an oral selective melanocortin 1 receptor agonist that increases eumelanin production. Three randomized placebo-controlled trials have been completed in these disorders. The phase 2 ENDEAVOR trial randomized 102 adults to placebo or dersimelagon 100 mg or 300 mg once daily; the least-squares mean difference from placebo in change from baseline to week 16 in average daily time to first prodromal symptom was 53.8 minutes at 100 mg (P = 0.008) and 62.5 minutes at 300 mg (P = 0.003). The first phase 3 trial, MT-7117-G01, randomized 184 adults and adolescents to two undisclosed doses or placebo and did not meet its primary endpoint at week 26: the least-squares mean difference from placebo was 9.8 minutes at the low dose (95% confidence interval -18.52 to 38.12; P = 0.496) and 22.7 minutes at the high dose (95% confidence interval -5.68 to 51.09; P = 0.116). Because sequential testing stopped at that point, all secondary P values from that trial are nominal. The second phase 3 trial, INSPIRE, randomized 165 participants aged 12 to 75 years, 82 to dersimelagon 200 mg once daily and 83 to placebo, and met its primary endpoint over weeks 12 to 16 with a placebo-adjusted least-squares mean difference of 23.19 minutes (P = 0.004); the presenter reported that time to prodrome was similar between groups at week 16 alone. Patient Global Impression of Change differed by -1.83 points (P < 0.001) and total pain events were 39% lower (P = 0.004). No INSPIRE results have been posted to any registry and no peer-reviewed publication exists. Reported adverse events across the program are consistent with the mechanism and include melanocytic nevi, skin hyperpigmentation, nausea, headache, and diarrhea. One death occurred, from cholestasis in the high-dose arm of MT-7117-G01, assessed as probably related by the investigator and unlikely or unrelated by the sponsor. One serious treatment-emergent adverse event in INSPIRE was a malignant melanoma in situ identified on day 36 in a participant with a family history of melanoma and a pre-existing lesion.