Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study

Wiping Out CGRP: Potential Cardiovascular Risks

“…Thus far, the results from the Phase II clinical trials evaluating the efficacy and tolerability of antibodies directed against CGRP or the CGRP receptor are promising [16,17,[38][39][40]. This is potentially good news for patients with migraine or (possibly) cluster headache because specifically designed, effective, and well-tolerated prophylactic agents against these diseases are currently not available.…”

“…However, these studies were performed in normal, anesthetized animals without pre-existing or induced ischemia. In patients with migraine, no cardiovascular adverse events were observed in five, relatively small and short-lasting, Phase II clinical trials with four different antibodies directed against CGRP or its receptor [16,17,[38][39][40]. The issue of cardiovascular safety was specifically addressed in two small studies, one in 31 healthy women [41] and another in 56 cynomolgus monkeys [42].…”

Anti-CGRP monoclonal antibodies in migraine: current perspectives

“…At 9-12 weeks vs baseline, while, in the placebo group, there was a least square mean (LSM) change in number of migraine days of -3.46 ± 5.40, the change was -6.27 ± 5.38 for TEV-48125 at 225 mg and -6. The authors conclude that both doses of TEV-48125 are effective and safe in migraine prevention when delivered at the regimen of 3 administrations over a 12-week period, thus supporting the plan to perform phase 3 clinical trials in this field [89].…”

“…Nevertheless, in a recently published article, Pasqual [94] underlined how, in the trials with TEV-48125, 45 % of patients who received high doses and 47 % of those receiving low doses do not meet the main goal of a 50 % reduction of moderate or severe headache days, normally regarded as the basic positive outcome of a preventative regimen [89,90]. Among the reasons for the apparent lack of satisfactory effects of CGRP antibodies in some patients, the author considers the multifactorial nature of migraine pathophysiology, with other molecules in addition to CGRP (e.g., vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, glutamate) involved in pain generation [95].…”

Headache Highlights 2016: Junior Editors’ Choice

“…Consequently, CGRP antagonists and antibodies have reached phase IIb and phase III clinical trials. In late 2015, Bigal et al published the results of two multicentre randomised double-blind placebo-controlled phase IIb clinical trials of TEV-48125, a subcutaneously administered monoclonal anti-CGRP antibody, for the preventive treatment of episodic and chronic migraine (7,8). For episodic migraine, the investigators demonstrated that during the third cycle (weeks 9-12), there was a significant difference between the reduction in migraine headache days in the group receiving the study drug as compared to placebo of 2.8 days in patients given 225 mg and 2.6 days in patients given 675 mg of TEV-48125 when the drug was given once a month for three months.…”