Dr Sheena K AuroraSheena K. Aurora, MBBS
The humanized monoclonal antibody against calcitonin gene-related peptide (CGRP), galcanezumab, has now been shown to be efficacious in comparison to placebo in reducing mean monthly migraine days in those with chronic migraine and history of preventive treatment failures.

Additionally in this randomized phase 3 clinical trial (NCT02614261), the Eli Lilly product, marketed as Emgality, was also shown to be superior in other key outcomes, including ≥50% and ≥75% responder rates, reductions in acute medication use, and enhancements in Migraine-Specific Quality of Life Questionnaire Role Function Restrictive (MSQ RF-R) domain scores.

The investigators, including Sheena K. Aurora, MBBS, Medical Fellow, Global Launch Leader, Eli Lilly, and colleagues wrote that these data “suggest that galcanezumab is efficacious in patients with chronic migraine who have previously failed other migraine preventive treatments and may also be suitable in patients without any prior preventive treatment failure.” They added that it may be a viable option for those with high unmet need and who may be at risk of managing their disease with only acute medications.

All told, the trial included 1113 patients, randomizing them 2:1:1 to placebo (n = 558), a 120-mg dose (n = 278), and a 240-mg dose (n = 277). From baseline to Month 3, the number of monthly migraine days was improved significantly (P <.01) in patients with ≥2 prior failures. The reductions were by 5.35 days (standard error [SE], 0.54) and 5.53 days (SE, 0.60) with the 240-mg and 120-mg doses, respectively, compared to 2.02 days (SE, 0.49) with placebo.

Of the patients with ≥2 prior failures treated with galcanezumab, 29.6% (SE, 4.7) and 18.7% (SE, 3.3) of patients in the 120- and 240-mg arms experienced a ≥50% reduction of monthly mean headache days, respectively. In those who only had ≥1 prior failure those rates of ≥50% reduction were 31.2% (SE, 3.7) and 20.5% (SE, 3.0), respectively. In comparison, only 11.3% (SE, 1.7) of placebo patients experienced this reduction (P <.01).

This significant difference was also shown with galcanezumab 120-mg and 240-mg, respectively, in a subgroup of patients with ≥3 prior failures, reducing monthly migraine days by 5.64 days (SE, 0.97) and 1.74 days (SE, 0.91) compared to 0.39 days (SE, 0.76) with placebo (P <.001).

“This was likely driven by the lower placebo response in patients with prior failures (2 and 1) versus no prior failures, as the galcanezumab responses were comparable across subgroups,” Aurora and colleagues detailed. “Similar to results reported here, in phase 2b and phase 3b studies of erenumab, a monoclonal antibody against [the] CGRP receptor, lower placebo response was seen in patients with prior failure (2 or 1) versus no prior failure.”

They added that the relationship between placebo response and patient expectations is a complex one. It is possible, they noted, that a lower placebo response in patients with prior failures could be reflective of similarly lower expectations with these patients. “On the other hand, the subgroup with a history of never receiving or never failing a preventive treatment may have more optimistic expectations,” they wrote.

As well, significantly larger overall reductions from baseline were observed in mean monthly migraine days with acute medication use for in patients with ≥2 prior failures. Those reductions were 5.81 days (SE, 0.69) and 3.40 days (SE, 0.65) in the 120- and 240-mg arms, respectively, compared to placebo’s reduction of 1.35 days (SE, 0.53; P <.05).

MSQ RF-R domain scores were improved by 19.13 (SE, 2.87) with 120-mg galcanezumab and 19.24 (SE, 2.61) with 240-mg galcanezumab in patients with ≥2 failures. In comparison, placebo scores improved by 10.67 (SE, 2.12). Similar results were seen in patients with ≥1 failure (overall P <.05).

“The results of this study are important, given that clinicians will need to evaluate the best treatment options for this subgroup of patients with high unmet need who have been treated previously with preventives but failed to respond or discontinued for safety- and/or tolerability-related reasons,” the investigators wrote.

They concluded noting that those who are challenged with these patients might “perceive that this subpopulation is less likely to respond to any preventive migraine treatment,” but should be aware that this work showed “consistent results across patients with different histories of prior preventive failures” in a number of outcomes.
Ruff DD, Ford JH, Tockhorn-Heidenreich A, et al. Efficacy of galcanezumab in patients with chronic migraine and a history of preventive treatment failure. Cephalagia. Published online May 19, 2019. doi: 10.1177/0333102419847957.