Galcanezumab Treatment Research Articles

Anti-CGRP antibody galcanezumab modifies the function of the trigeminovascular nocisensor complex in the rat

BackgroundMonoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) are effective in the prevention of chronic and frequent episodic migraine. Since the antibodies do not cross the blood brain barrier, their antinociceptive effect is attributed to effects in meningeal tissues. We aimed to probe if such an antibody can be visualized within the dura mater and the trigeminal ganglia following its administration to rats and to examine if the activity of the trigeminovascular nocisensor complex is influenced by this treatment.MethodsEffects of the anti-CGRP antibody galcanezumab on the trigeminovascular nocisensor complex was examined by measuring release of sensory neuropeptides and histamine from the rat dura mater. Deposits of galcanezumab were visualized by fluorescence microscopy in the trigeminal ganglion and the dura mater.ResultsFluorophore-labelled galcanezumab was detected in the dura mater and the trigeminal ganglion up to 30 days after treatment affirming the long-lasting modulatory effect of this antibody. In female rats, seven days after systemic treatment with galcanezumab the capsaicin-induced release of CGRP was decreased, while that of substance P (SP) was increased in the dura mater. In control rats, release of the inhibitory neuropeptide somatostatin (SOM) was higher in females than in males. Stimulation with high concentration of KCl did not significantly change the release of SOM in control animals, while in rats treated with galcanezumab SOM release was slightly reduced. Galcanezumab treatment also reduced the amount of histamine released from dural mast cells upon stimulation with CGRP, while the effect of compound 48/80 on histamine release was not changed.ConclusionsGalcanezumab treatment is followed by multiple changes in the release of neuropeptides and histamine in the trigeminal nocisensor complex, which may contribute to the migraine preventing effect of anti-CGRP antibodies. These changes affecting the communication between the components of the trigeminal nocisensor complex may reduce pain susceptibility in migraine patients treated with CGRP targeting monoclonal antibodies.

Real-life experiences with galcanezumab and predictors for treatment response in Turkey

BackgroundThe complexity of clinical practice extends far beyond the controlled settings of trials, and there is a need for real-world studies aimed at identifying which patients will respond to anti-CGRP monoclonal antibodies in different countries. This study aimed to investigate the efficacy and safety of galcanezumab in treating migraine in a real-life setting in Turkey, as well as identify predictors of treatment response.MethodsA total of 476 patients who diagnosed with migraine according to ICHD-3 criteria and treated with galcanezumab by headache specialists were voluntarily participated in this cross-sectional study. Galcanezumab is indicated for the prevention of migraine in adults who have at least 4 monthly migraine days in Turkey. All patients filled out a survey on Google Form that comprised 54 questions, addressing various aspects such as demographics, migraine characteristics, previous use of acute symptomatic medication, failures with preventive drug classes, comorbidities, most bothersome symptoms, as well as the interictal burden of migraine.ResultsAmong the participants, 89.3% reported that galcanezumab treatment was beneficial for them. A decrease in the frequency (80.0%), severity (85.7%), and acute medication usage for migraine attacks (71.4%) was reported with galcanezumab treatment. An adverse effect related to galcanezumab was reported in 16.3% of cases, but no serious adverse reactions were observed. Remarkably, 14.3% of participants reported no longer experiencing any headaches, and 18.9% did not require any acute treatment while receiving galcanezumab treatment. A logistic regression model showed that male gender, lack of ictal nausea, and previous failure of more than 2 prophylactic agents may predict the non-responders.ConclusionsThe first large series from Turkey showed that galcanezumab treatment is safe and effective in most of the patients diagnosed with migraine by headache experts in the real-life setting. Patients reported a significant decrease in both ictal and interictal burden of migraine and expressed satisfaction with this treatment.

Predictors of galcanezumab response in a real-world study of Korean patients with migraine

To assess factors associated with galcanezumab response in a real-world study of Korean patients with migraine. Predictors of the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP(-R) mAb) have been rarely investigated in Asians. We prospectively recruited and followed up patients with migraine who received monthly galcanezumab treatment in a single university hospital from June 2020 to October 2021. We defined the treatment response with ≥ 50% reduction in moderate/severe headache days in the 3rd month of treatment compared to baseline. Responders and non-responders were compared in terms of demographics, disease characteristics and severity, and previous response to migraine prophylactic treatments. Potential predictors of anti-CGRP(-R) mAb response were tested by using the univariable and multivariable logistic regression analyses. Among 104 patients (81.7% female; mean age 42.0 ± 13.02; 76.9% chronic migraine; and 45.5% medication overuse headache) included, 58 (55.7%) were responders. Non-responders had more chronic migraine, medication overuse headache, monthly headache days, days with acute medication, and daily headaches (i.e. chronic migraine persisting everyday without remission). The multivariable logistic analysis showed chronic migraine (OR 0.05 [95% CI 0.00–0.82], p = 0.036) and the number of previously failed preventive medication classes (OR 0.55 [95% CI 0.33–0.92], p = 0.024] were independently associated with treatment response. Chronic migraine and multiple failures from preventive medication are associated with poor galcanezumab response. Further studies are needed to investigate if earlier treatment before disease chronification or multiple failures may lead to a greater therapeutic gain from anti-CGRP(-R) mAb treatment.

Switching from galcanezumab to fremanezumab in migraine patients: a retrospective analysis (P7-12.011)

Switching from galcanezumab to fremanezumab in migraine patients: a retrospective analysis (P7-12.011)

Predictors of response to galcanezumab in patients with chronic migraine: a real-world prospective observational study.

Despite high efficacy and tolerability, not all patients with chronic migraine benefit from anti-CGRP monoclonal antibodies. We aimed to identify the clinical predictors of the response to galcanezumab treatment in patients with chronic migraine from real-world data. We prospectively recruited patients with CM who underwent galcanezumab injections between December 2019 and February 2022. Treatment response was determined after three months of follow-up and was defined as ≥ 50% reduction in monthly headache days. The migraine characteristics, comorbidities, and other treatment responses were compared between the responder and non-responder groups. Of 238 patients with CM, 153 (64.3%) showed treatment response. The responder group was younger, had lower frequency of baseline headache days, and had more accompanying symptoms such as nausea, vomiting, and photophobia. Better triptan response and less depression were also observed in the responder group. Multivariable regression analysis revealed that the everyday headache (OR = 0.351, 95% CI = 0.133-0.874, p = 0.017), depression (OR = 0.439, 95% CI = 0.216-0.896, p = 0.024) and absence of accompanying symptoms (OR = 0.314, 95% CI = 0.118-0.834, p = 0.020) were significantly associated with response to galcanezumab treatment. Our real-world data showed the efficacy of galcanezumab in patients with CM, regardless of medication overuse. Everyday headache, presence of depression, and absence of accompanying symptoms of migraine were significant predictors of a poor response.

Efficacy and Safety of Galcanezumab as a Preventive Treatment for Episodic Migraine in South Korean Patients: A Post-Hoc Analysis of a Phase 3 Clinical Trial.

The estimated prevalence of migraines in South Korea is 6.0%, with affected patients having unmet needs. The efficacy, safety, and tolerability of galcanezumab, a humanized monoclonal antibody, for episodic migraine (EM) prevention was evaluated in South Korean patients. During the double-blind period of the EVOLVE-2 phase 3 trial, patients with EM were randomized into placebo, 120 mg-galcanezumab, and 240-mg galcanezumab treatment groups. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days during the 6-month double-blind period. We conducted a post-hoc analysis of the South Korean cohort in EVOLVE-2. Among 98 South Korean patients in the intent-to-treat population, significant changes from baseline were observed in the number of monthly migraine headache days in the 240-mg galcanezumab group compared with the placebo group (-2.64, p=0.013), in the percentage of patients with ≥50% reduction in the number of monthly migraine headache days (120 mg: odds ratio=2.43, p=0.030; 240 mg: odds ratio=2.60, p=0.019), in the number of monthly migraine headache days with acute medication use (120 mg: -2.22, p=0.006; 240 mg: -2.23, p=0.005), and in the Migraine-Specific Quality-of-Life Role Function-Restrictive (120 mg: 8.34, p=0.040). Numerical improvements from baseline were observed relative to the placebo group in at least one galcanezumab group for: the percentage of patients with ≥75% reduction in the number of monthly migraine headache days functional impairment, and disease severity. The most common treatment-emergent adverse event in the combined galcanezumab group was injection site reaction, which led to treatment discontinuation for one patient. Galcanezumab treatment demonstrated efficacy and a favorable safety and tolerability profile in South Korean patients with EM.

Improving distress perception and mutuality in migraine caregivers after 6months of galcanezumab treatment.

This prospective cohort, real-life study aimed to evaluate whether galcanezumab, a monoclonal antibody anti-calcitonin gene-related peptide (CGRP) ligand, can reduce caregivers' distress and improve their mutuality with patients. Migraine is a highly disabling chronic disease that negatively impacts patients' and often their relatives' lives, occurring during an active phase of life with direct consequences on leisure- and work-related activities. The figure of caregiver is crucial in several neurological conditions but poorly accounted for in migraine care so far. Studies on monoclonal antibodies against the CGRP pathway, recently introduced as migraine-preventive treatments, demonstrated that they significantly reduce migraine frequency and disability in the first weeks of treatment. Consecutive patient-caregiver dyads were evaluated at baseline and after 6months of treatment with galcanezumab (V6) at our headache center from September 2020 to September 2021. Enrolled patients were requested to report their monthly migraine days, monthly intake of acute medications, attack pain intensity (on the Numeric Rating Scale), concomitant preventives, and disability questionnaires (Headache Impact Test, Migraine Disability Assessment). Each dyad filled in the Mutuality Scale to check their reciprocity; moreover, the Relatives' Stress Scale was used to detect caregivers' distress. We enrolled 27 patient-caregiver dyads. At 6months, migraine burden significantly improved with reductions in monthly migraine days (falling from 14.8 [SD=4.8] days by 10.3 [SD=4.8] days; 95% CI: 8.4, 12.2; p< 0.001) and Migraine Disability Assessment scores (lowering from 83.6 [SD=46.7] by 71.5 points [SD=49.3]; 95% CI: 51.2, 91.9; p< 0.001). From baseline to month 6, the caregiver Relatives' Stress Scale score significantly decreased (falling from 20.7 [SD=13.7] by 6.5 [SD=14.1] points; 95% CI: 0.8, 12.2; p= 0.027), while the Mutuality Scale's caregiver total score increased (from 3.04 [SD=0.61] by 0.29 [SD=0.49] points; 95% CI: -0.508, -0.064; p= 0.014). Our findings preliminarily demonstrated that patients' migraine improvement after 6months of galcanezumab treatment could be favorably perceived by caregivers, significantly reducing their distress with better reciprocity within the dyad.

Real-world efficacy of galcanezumab for the treatment of migraine in Korean patients

We aimed to provide real-world data on the effectiveness of an anti-calcitonin gene-related peptide monoclonal antibody administered for treating migraine in Korean patients. We prospectively recruited patients with migraine who received galcanezumab treatment at a single university hospital from June 2020 to April 2021. The treatment response was assessed after three consecutive monthly injections. A 50% responder rate was evaluated based on ≥50% reduction in the number of moderate/severe headache days. Overall, 87 patients were included in the analysis. Most patients were women (83.9%). They had a mean age of 41.7 ± 12.3 years (range 17-72). Sixty-five patients (74.7%) had chronic migraine, 35 patients (40.2%) had a history of medication-overuse headache, and 32 patients (36.8%) were previously unresponsive to or found intolerable five classes of preventive medication. After three months of treatment, mean changes in numbers of monthly headache days, moderate/severe headache days, crystal clear days, and days of acute medication use were -7.2 ± 8.43, -4.3 ± 9.76, 7.3 ± 8.50, and -4.1 ± 7.93, respectively. The 50% responder rates were 58.3%, 44.2%, and 40.6% for patients with unsuccessful previous use of 0-1, 2-4, and 5 preventive medication classes, respectively. Headache Impact Test-6 and Migraine Disability Assessment Test scores also decreased (-4.4 ± 8.09 and -32.9 ± 77.04, respectively). In our cohort, the effectiveness and safety of galcanezumab were comparable with those reported in clinical trials, whereas a higher response rate was observed in the difficult-to-treat patient subset than that reported in trials. We provide real-world evidence of galcanezumab treatment benefits in Asian patients with migraine.

Treatment satisfaction with calcitonin gene-related peptide monoclonal antibodies as a new patient-reported outcome measure: A real-life experience in migraine.

To evaluate treatment satisfaction with galcanezumab as a patient-reported outcome measure (PROM) in migraine. Patients with ≥8 headache days/month that had failed at ≥3medications were included. Demographic and medical history were collected. Patient´s satisfaction (effectiveness, safety, convenience, and global satisfaction [GS]) was assessed by the Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4©). We included 30 patients with migraine (76.7% chronic migraine). After 12weeks of galcanezumab treatment, median monthly headache days (MHDs) decreased 11.5 (IQR 14.0) and median monthly migraine days (MMDs) 9.0 (IQR 7.5); at 24weeks, the change was 15.0 (IQR 12.0) and 8.0days (IQR 6.0). HIT-6 score decreased from 68.0 (IQR 7.5) to 54.0 (IQR 9.5) at 12weeks (p<.001) and to 52.0 (IQR12.0) at 24weeks (p<.001) and MIDAS from 60.0 (IQR 62.7) to 25.5 (IQR 41.2, p=.004) and 7.0 (IQR 18.5, p<.001), respectively. TSQM-1.4© at 12weeks was higher compared to other preventive therapy in effectiveness (80.6/50.4, p<.001), convenience (83.3/66.7, p=.001), and GS (78.6/50.0, p<.001). These rates of satisfaction were similar at 24weeks of galcanezumab treatment. Reductions in HIT-6 (r=-.444, p=.014), MIDAS (r=-.423, p=.020), MMDs (r=-.515, p=.004), and MHDs (r=-.477, p=.008) were associated significantly with GS at 12weeks. This correlation was significantly associated with changes in HIT-6 and MHDs at 24weeks. The results of this study suggest that migraine patients receiving galcanezumab are significantly more satisfied compared to other preventive therapies, associating treatment GS with meaningful reductions in frequency, impact, and disability caused by migraine.

Trigeminal sensory modulatory effects of galcanezumab and clinical response prediction.

Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, is an emerging migraine preventative. We hypothesized that the preventive effects are conveyed via the modulation of somatosensory processing and that certain sensory profiles may hence be associated with different clinical responses. We recruited migraine patients (n = 26), who underwent quantitative sensory tests over the right V1 dermatome and forearm at baseline (T0), 2 to 3 weeks (T1) and 1 year (T12) after monthly galcanezumab treatment. The clinical response was defined as a reduction of ≥30% in headache frequency based on the headache diary. Predictors for clinical response were calculated using binary logistical regression models. After galcanezumab (T1 vs T0), the heat pain threshold (°C, 44.9 ± 3.4 vs 43.0 ± 3.3, P = 0.013) and mechanical pain threshold (log mN, 1.60 ± 0.31 vs 1.45 ± 0.26, P = 0.042) were increased exclusively in the V1 dermatome but not the forearm. These changes were immediate, did not differ between responders and nonresponders, and did not last in 1 year of follow-up (T12 vs T0). However, baseline heat pain threshold (OR: 2.13, 95% CI: 1.08-4.19, P = 0.029) on the forearm was a robust predictor for a clinical response 3 months later. In summary, our data demonstrated that galcanezumab modulates pain thresholds specifically in the V1 dermatome, but this modulation is short-lasting and irrelevant to clinical response. Instead, the clinical response may be determined by individual sensibility even before the administration of medication.

Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures

BackgroundGalcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives.MethodsPatients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.ResultsGalcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo − 0.2; galcanezumab − 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1–3 (all p < 0.05) and at weeks 1–4 of month 1 compared to placebo (all p < 0.01).ConclusionGalcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments.Trial registrationClinicalTrials.gov, NCT03559257. Registered 18 June 2018.

Safety and efficacy of galcanezumab in Taiwanese patients: a post-hoc analysis of phase 3 studies in episodic and chronic migraine

Objective Migraine is a chronic, disabling neurological disease affecting >1 billion people worldwide. Migraine remains undertreated in Asia, including Taiwan. Galcanezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide, a peptide firmly established in the pathophysiology of migraine, with demonstrated efficacy and safety in patients with episodic or chronic migraine. Our objective was to evaluate the efficacy and safety of galcanezumab in Taiwanese patients with episodic or chronic migraine. Methods We conducted a sub-group analysis of the Taiwanese cohort from two double-blind, placebo-controlled, Phase 3 clinical trials of galcanezumab in the prevention of episodic and chronic migraine, EVOLVE-2 (NCT02614196) and REGAIN (NCT02614261), respectively. During the EVOLVE-2 and REGAIN double-blind periods, 2092 patients were randomly assigned to receive monthly injections of either placebo, 120 mg galcanezumab (240 mg loading dose), or 240 mg galcanezumab. In REGAIN, a 9-month open-label period followed. Post-hoc analysis on the Taiwanese population across both trials included 106 patients, 45 of whom continued into the open-label period in REGAIN. Results Our findings show that galcanezumab has similar efficacy and safety in the Taiwanese population, as compared to the “All Patients” population included in the study. Galcanezumab treatment reduced the number of monthly migraine headache days, determined a higher percentage of patients with a ≥ 50% response, and positively impacted quality of life. Conclusion Galcanezumab is a promising therapeutic for the preventive treatment of migraine in the Taiwanese population.

Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials

BackgroundMigraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine.MethodsAnalyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN:N = 1113). Patients were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. Safety and PK data included additional phase 2 and phase 3 trials for a larger sample size of patients > 60 years (range = 18–65 for all studies). Subgroup analyses assessed efficacy measures, adverse event (AE) occurrence, and cardiovascular measurement changes by patient age group. Galcanezumab PK were evaluated using a population analysis approach, where age was examined as a potential covariate on apparent clearance (CL/F) and apparent volume of distribution (V/F) of galcanezumab.ResultsNumbers of baseline monthly migraine headache days were similar across age groups. There were no statistically significant treatment-by-age group interactions for any efficacy measures, except in episodic migraine studies where older patients appeared to have a larger reduction than younger patients in the number of monthly migraine headache days with acute medication use. Age (18–65) had a minimal effect on CL/F, and no effect on V/F. Galcanezumab-treated patients ≥60 years experienced no clinically meaningful increases in blood pressure and no increased frequency in treatment-emergent AEs, discontinuations due to AEs, serious adverse events (SAEs) overall, or cardiovascular SAEs, compared to age-matched placebo-treated patients.ConclusionsAge (up to 65 years) does not affect efficacy in migraine prevention and has no clinically meaningful influence on galcanezumab PK to warrant dose adjustment. Furthermore, older galcanezumab-treated patients experienced no increases in frequency of AEs or increases in blood pressure compared with age-matched placebo-treated patients.Trial registrationsEVOLVE-1 (NCT02614183, registered 23 November 2015), EVOLVE-2 (NCT02614196, 23 November 2015), REGAIN (NCT02614261, 23 November 2015), ART-01 (NCT01625988, 20 June 2012, ), I5Q-MC-CGAB (NCT02163993, 12 June 2014, ), I5Q-MC-CGAJ (NCT02614287, 23 November 2015, ), all retrospectively registered.

Galcanezumab: A Review in the Prevention of Migraine and Treatment of Episodic Cluster Headache.

Galcanezumab (Emgality®) is a humanized monoclonal antibody targeting the calcitonin gene-related peptide (CGRP), thereby inhibiting its physiological activity, with CGRP playing a key role in the pathophysiology of migraine and headache disorders. In pivotal phase 3 trials, recommended dosages of subcutaneous galcanezumab once monthly were significantly more effective than placebo as preventive therapy in adults with episodic (EVOLVE-1 and -2; over 6months) or chronic (REGAIN; over 3months) migraine (± aura), including in patients who had failed several prior preventive migraine drugs (CONQUER; over 3months). The beneficial effects of galcanezumab preventive treatment in reducing the number of monthly migraine headache days (MHDs) and improving health-related quality of life (HR-QOL) were sustained during up to 1year of treatment. In adults with episodic cluster headache, galcanezumab treatment was associated with a significant reduction in the weekly frequency of cluster headache attacks across weeks 1-3 compared with placebo (primary endpoint), albeit during weeks 4-8, there was a convergence of results between these treatment groups. Although further evidence from the clinical setting is required to determine its long-term safety profile, given its convenient administration regimen, efficacy and short-term tolerability profile, monthly galcanezumab represents an important emerging option for the prevention of episodic and chronic migraine (± aura) and the treatment of episodic cluster headache.

Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review.

Migraine is a debilitating neurologic disease. People who experience migraine can have substantial disability, impaired functioning and a decreased quality of life (QoL). Expert recommendations suggest that people with frequent migraine attacks or severe impairment related to attacks may benefit from preventive treatment. Despite these recommendations and the existence of evidence-based guidelines for the use of preventive medication, many people who are candidates for preventive therapies do not receive them. Thus, there is still a substantial unmet need for preventive migraine treatment. Calcitonin gene-related peptide (CGRP) has a demonstrated role in the pathophysiology of migraine. Galcanezumab-gnlm (galcanezumab) is a humanized monoclonal antibody that binds to the CGRP ligand and prevents binding to its receptor. It is administered as a once-monthly subcutaneous injection. The aim of this review is to present a comprehensive overview of the existing short- and long-term efficacy and safety data for galcanezumab in patients with migraine. Data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies show that galcanezumab treatment for 3 or 6 months results in overall reduction in mean monthly migraine headache days in patients with episodic (EVOLVE-1 and EVOLVE-2) and chronic (REGAIN) migraine. Greater proportions of patients with episodic migraine receiving galcanezumab versus placebo demonstrated a ≥ 50%, ≥ 75% and 100% response to therapy and reported a lower level of disability and an improvement in functioning and QoL. Similarly, when compared with placebo, greater proportions of patients with chronic migraine treated with galcanezumab demonstrated a ≥ 50% and ≥ 75% response and reported improved functioning. A 12-month open-label study demonstrated the continued efficacy of galcanezumab for up to 12 months. In all studies galcanezumab was well tolerated. In conclusion, data from pivotal studies show that galcanezumab may fulfill an unmet need in the treatment of patients with migraine who require preventive therapy.

Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination

BackgroundMonoclonal antibodies (mAbs) targeting the CGRP pathway are safe and efficacious therapies for the prevention of migraine. In this study we assessed the effects of discontinuation of preventive erenumab and galcanezumab treatment in patients with chronic migraine.MethodsThis retrospective pooled analysis included completers of the open-label extension study phase for the preventive treatment of chronic migraine with galcanezumab (NCT02614261; 9 months) and erenumab (NCT02174861; 12 months) in a single headache center. We compare migraine data until week 12 after open-label treatment completion, when patients did not have any pharmacological preventive medication, to study baseline values of the double-blind trial period, and to the last 4 weeks of the open-label extension. The assessment included changes in monthly migraine days, headache hours, days with severe headache and acute headache medication use.ResultsData from 16 patients after galcanezumab (n = 9) and erenumab (n = 7) open-label treatment completion were analyzed. The mean number of monthly migraine days was 18.38 ± 3.74 at baseline, and 12.19 ± 4.53 in the last 4 weeks of the open-label extension (p < 0.001). Monthly migraine days remained significantly reduced compared to baseline during the entire 12-week observation period after open-label termination (p = 0.002), with a reduction of 5.38 ± 4.92 in weeks 1–4 (p = 0.001), 4.75 ± 4.15 in weeks 5–8 (p = 0.001), and 3.93 ± 5.45 in weeks 9–12 (p = 0.014). There was no significant difference in monthly migraine days between the 12 weeks after open-label termination and the last 4 weeks of the open-label phase (p = 0.228). All other analyses revealed numerical improvement through week 12 in comparison to baseline.ConclusionsIn this small, self-selected cohort, the results indicate a therapeutic effect of monoclonal antibodies targeting the CRGP pathway in chronic migraine prevention after treatment termination up to 12 weeks.

Effect of Age on Efficacy and Safety of Galcanezumab Treatment in Adult Patients with Migraine (P2.10-021)

Effect of Age on Efficacy and Safety of Galcanezumab Treatment in Adult Patients with Migraine (P2.10-021)

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies.

ObjectiveTo examine the likelihood of response with continued galcanezumab treatment in patients with episodic or chronic migraine without initial clinical improvement.BackgroundA percentage of patients with migraine may require additional time on pharmacotherapy but discontinue treatment prematurely. Additionally, recognizing when continued treatment is unlikely to provide improvement limits unnecessary exposure.MethodsPost hoc analysis of response after continued galcanezumab treatment was conducted in a subset of patients with episodic (N = 879) and chronic (N = 555) migraine who did not achieve “good” early improvement (episodic, ≥50% reduction in baseline migraine headache days [MHD] and chronic, ≥30% reduction) after 1 month of dosing (NR‐1; episodic, n = 450 and chronic, n = 306). This subset was categorized by level of reduction in MHD during 1 month of treatment: “modest” (>30% to <50% fewer MHD for episodic and >10% to <30% fewer MHD for chronic), “limited” (episodic only; >10% to ≤30% fewer MHD), or “minimal/no” early improvement (≤10% fewer MHD to ≤10% more MHD), or “worsening” (>10% more MHD). The percentages of patients having “better” (≥75% fewer MHD for episodic and ≥50% for chronic), “good,” or “little‐to‐no” (≤10% fewer MHD) response during the remaining treatment period were calculated for each category. Similarly, the subset of NR‐1 patients who did not achieve “good” early improvement after 2 months of treatment (NR‐2; episodic, n = 290 and chronic, n = 240) were categorized by level of their average monthly reduction across 1 and 2 months using similar categories.ResultsOf NR‐1 patients with episodic migraine having “modest” early improvement, 62% (96/155) achieved “good” and 20% (31/155) achieved “better” responses with continued treatment. A percentage of patients with “limited” (43%; 46/108) or “minimal/no” (34%; 29/85) early improvement, or “worsening” (20%; 20/102) achieved a “good” response after continued treatment. A percentage of NR‐1 patients with chronic migraine having “modest” early improvement achieved “good” (38%; 44/116) and “better” (13%; 15/116) responses with continued treatment. A “good” response was achieved for a percentage of patients with “minimal/no” early improvement (17%; 23/133). Similar patterns were observed for the NR‐2 subset, though percentages were lower.ConclusionsGalcanezumab‐treated patients with episodic or chronic migraine without response following 1 or 2 months of treatment appear to have a reasonable likelihood of continued improvement in months following initial treatment and this opportunity is more likely in patients showing greater early improvements. While a small percentage of patients with episodic or chronic migraine who experienced worsening in the number of MHD following initial treatment responded with continued treatment, most do not show substantial reduction in MHD. Overall benefit of therapy should be determined collaboratively between the patient and physician.

Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study.

Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here. Methods Patients aged 18-65 years with episodic migraine were evaluated in this multicenter, double-blind, randomized study. After randomization, 410 patients were administered 5, 50, 120 or 300 mg of galcanezumab or placebo subcutaneously once every 4 weeks for 12 weeks, followed by a post-treatment off-drug period lasting 12 weeks. Results Treatment-emergent adverse events (TEAEs) were primarily rated as mild to moderate. Serious adverse events reported in galcanezumab dose groups were appendicitis, Crohn's disease, suicidal ideation, and congenital ankyloglossia in an infant of a paternal pregnancy; each of these were reported by one patient. Adverse events leading to discontinuation with galcanezumab treatment were abdominal pain, visual impairment, and upper limb fracture, each reported by one patient. Treatment-emergent injection-site reactions were reported significantly more frequently ( p = 0.013) with galcanezumab (13.9%) than with placebo (5.8%). Injection-site pain was the most common injection-site reaction (galcanezumab 11.4%; placebo 2.9%, p = 0.004). Upper respiratory tract infection (galcanezumab 10.0%; placebo 8.8%) and nasopharyngitis (galcanezumab 7.0%; placebo 2.2%) also occurred more frequently with galcanezumab treatment. Potential hypersensitivity events were reported at similar frequencies in galcanezumab (3.3%) and placebo (5.1%) groups. Incidence of treatment-emergent anti-drug antibodies in galcanezumab dose groups (4.6% of patients during treatment period) did not appear to have any meaningful effects on safety, the pharmacokinetics of galcanezumab, or its ability to bind to the target ligand. Conclusion The results from this 3-month Phase 2b study support the initiation of larger Phase 3 trials of longer duration.