Emgality® (Galcanezumab)

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How should a patient be switched from another CGRP monoclonal antibody to galcanezumab for migraine prevention?

Information on switching from another CGRP mAb to galcanezumab for migraine prevention has not been systematically studied. Clinicians should use their judgment to determine whether a patient is a candidate for switching from one CGRP mAb to another.

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Switching From Another CGRP Monoclonal Antibody

Galcanezumab has been studied in phase 3, randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

  • episodic migraine (EVOLVE-1 and EVOLVE-2)1,2
  • chronic migraine (REGAIN),3 and
  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).4

Patients were excluded from study enrollment in these studies if they had prior or current exposure to

  • galcanezumab, or
  • another CGRP antibody.1-5 

The safety and efficacy of switching from 1 CGRP mAb to another for migraine prevention have not been systematically studied.

Clinicians are encouraged to use their independent clinical judgment to determine whether an individual patient is a candidate for switching from 1 CGRP mAb to another for migraine prevention. Decisions regarding the optimal time between taking 1 CGRP mAb and switching to another are best determined based on clinician and patient agreement that take into account the patient’s situation, needs, and preference.

Considerations Regarding Loading Dose of Galcanezumab When Switching From Another CGRP mAb Therapy

Most CGRP mAb therapeutic regimens, including galcanezumab, are commonly dosed monthly.5,6

The recommended galcanezumab dose is 120 mg injected subcutaneously once monthly, with a 240-mg loading dose as the initial dose.5

Pharmacokinetic modeling of phase 3 data confirmed that

  • the 240-mg loading dose achieved steady-state galcanezumab concentrations by month 1 for the 120-mg monthly dose regimen, and
  • without a loading dose, the 120-mg monthly dose did not achieve steady state until 4 to 5 months.7

Loading Dose at the Beginning of Open-Label Treatment in REGAIN and CONQUER Studies

The REGAIN study had a double-blind treatment duration of 3 months, with an optional 9-month open-label extension after completion of the double-blind phase. At the start of the double-blind treatment phase, patients were randomized in a 2:1:1 ratio to receive monthly subcutaneous injections of placebo, galcanezumab 120 mg with a 240-mg loading dose, or galcanezumab 240 mg.3

In this study, all patients who entered the open-label extension received a galcanezumab 240-mg loading dose at the first open-label dosing visit to maintain the blind to treatment assignment during the double-blind phase.5

CONQUER had a double-blind treatment duration of 3 months, with an optional 3-month open-label extension phase. Patients were randomized in a 1:1 ratio to receive monthly subcutaneous injections of placebo or galcanezumab 120 mg with a loading dose of 240 mg at the beginning of double-blind treatment.4

After completing double-blind treatment in CONQUER, patients could enter an open-label extension in months 4 to 6, in which all patients received galcanezumab 120 mg monthly.8

All patients received 2 injections to allow for blinded 240-mg loading dose of galcanezumab at month 3. Specifically,

  • patients randomized to placebo during double-blind treatment received a loading dose of galcanezumab 240 mg, and
  • patients randomized to galcanezumab during double-blind treatment received 1 injection of galcanezumab 120 mg and 1 injection of placebo.8

Subgroup analyses between patients who were randomized to placebo during the double-blind period compared with those who were randomized to active treatment during the double-blind period in the REGAIN and CONQUER studies are not available.

Real World Data: Switching From Another CGRP mAb to Galcanezumab

Limited real-world data on switching from another CGRP mAb to galcanezumab are available and are summarized below.9-11  

The safety and efficacy of switching from biologics has been explored in other disease states and are discussed in: Appendix: Efficacy and Safety of Switching From Biologics in Other Disease States . 

Retrospective Chart Review

The experiences of patients in a tertiary headache center who switched from erenumab to galcanezumab were evaluated in a retrospective chart review. This analysis included a review of 3789 prescriptions for erenumab or galcanezumab, of which there were 100 patients who switched from erenumab to galcanezumab (68 patients were still taking galcanezumab at the time of the chart review).10

On average, patients were on

  • erenumab for 7 months prior to switching to galcanezumab, and
  • galcanezumab for 4.8 months after the switch.10

In patients who switched from erenumab to galcanezumab, a similar percentage of patients reported improvement with erenumab and galcanezumab (51% and 50%, respectively). Other responses to treatment reported were

  • initial improvement then worsening back to baseline (11% of erenumab patients vs 2% of galcanezumab patients), and
  • no improvement (35% of erenumab patients vs 29% of galcanezumab patients).10

The most common reason for discontinuation in both groups was for lack of efficacy (53% erenumab vs 21% galcanezumab).10

The most common side effects reported were

  • constipation in erenumab-treated patients (35% erenumab vs 8% galcanezumab), and
  • injection site reactions in galcanezumab-treated patients (1% erenumab vs 10% galcanezumab).10

Case Series

A case series discussed 3 female patients suffering from chronic and episodic migraine and their experience with preventative medications prior to switching to galcanezumab.11

Each patient was switched from therapy with erenumab (70 mg or 140 mg per month for 3 or 6 months) to galcanezumab 120 mg (loading dose of 240 mg). Prior to erenumab, different preventative medications included topiramate, metoprolol, flunarizine, amitriptyline, propranolol, opipramol, valproate, or onabotulinum toxin A.11

A switch to galcanezumab 120 mg per month lead to a significant decrease in headache days in all 3 patients after 3 months of treatment. The number of headache days per month in the 3 patients ranged from

  • 10 to 20 before galcanezumab, and
  • 1 to 7 after galcanezumab.11

OVERCOME STUDY

Patient-reported reasons for starting, switching, and stopping CGRP mAbs (erenumab, fremanezumab, and galcanezumab) were assessed from a web-based survey conducted in the United States. Of the 20,782 respondents, 950 patients reported ever using ≥1 CGRP mAb for the preventive treatment of migraine.9

Of the 950 CGRP mAb users, 11.8% (n=112) had switched between mAbs. Although there are no data explaining how patients were switched between CGRP mAbs, the reasons for switching are provided in Patient Reasons for Switching Between CGRP mAbs: OVERCOME Study.9

Patient Reasons for Switching Between CGRP mAbs: OVERCOME Study9

Patient Reasons for CGRP mAb Use Behavior

Switcheda
n (%)

Efficacyb

57 (50.9)

Dosing or deliveryc

36 (32.1)

Recommendation or requestd

47 (42.0)

Tolerabilitye

28 (25.0)

Access or economicsf

54 (48.2)

Novelg

NA

Disease resolutionh

NA

Stigmai

NA

Other

2 (2.0)

Abbreviations: CGRP = calcitonin gene-related peptide; mAb = monoclonal antibody; NA = not applicable.

aSwitched = still taking a CGRP mAb but not the initial CGRP mAb.

bEfficacy: reasons pertaining to a medication working/not working (or believed to potentially work) by itself or compared with another medication, a specific outcome (eg, headache-free days, 50% to 100% response), or achieving a functional outcome.

cDosing or delivery: reasons pertaining to the delivery method (eg, autoinjector, prefilled syringe), dosing regimen/schedule, or ease of use.

dRecommendation or request: reasons pertaining to the recommendation of a healthcare provider or family/friend, or personal request by the patient.

eTolerability: reasons pertaining to side effects, drug-drug interaction, comorbid condition, or safety over time.

fAccess or economic: reasons pertaining to insurance coverage, out-of-pocket costs, being given free samples, or affordability.

gNovel: single-item “Is different from other migraine or severe headache treatments available."

hDisease resolution: single-item “My migraine/severe headaches got better."

iStigma: single-item “I did not want anyone to think I was just someone who complains.”

References

1Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212

2Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543

3Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640

4Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. http://dx.doi.org/10.1016/S1474-4422(20)30279-9

5Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6Raffaelli B, Neeb L, Reuter U. Monoclonal antibodies for the prevention of migraine. Expert Opin Biol Ther. 2019;19(12):1307-1317. http://dx.doi.org/10.1080/14712598.2019.1671350

7Kielbasa W, Quinlan T. Population pharmacokinetics of galcanezumab, an anti-CGRP antibody, following subcutaneous dosing to healthy individuals and patients with migraine. J Clin Pharmacol. 2020;60(2):229-239. http://dx.doi.org/10.1002/jcph.1511

8Detke HC, Reuter U, Lucas C, et al. Galcanezumab in patients with treatment-resistant migraine: results from the open-label phase of the CONQUER phase 3 trial. Poster presented at: 14th European Headache Federation (EHF Virtual); June 29-July 2, 2020.

9Buse DC, Schuh K, Nicholson RA, et al. Patients' reasons for starting, switching, and stopping CGRP targeted monoclonal antibodies: results of the OVERCOME study. Cephalalgia. 2020;40(1_suppl):20-21. Migraine Trust Virtual 2020 – Digital presentations abstract MTV20-DP-003. https://dx.doi.org/10.1177/0333102420962305

10Pham A, Burch R. A real-world comparison of erenumab and galcanezumab in a tertiary headache center. Headache. 2020;60(suppl):4. 62nd Annual Scientific Meeting American Headache Society abstract. https://doi.org/10.1111/head.13854

11Ziegeler C, May A. Non-responders to treatment with antibodies to the CGRP-receptor may profit from a switch of antibody class. Headache. 2020;60(2):469-470. http://dx.doi.org/10.1111/head.13729

12Mrowietz U, de Jong EMGJ, Kragballe K, et al. A consensus report on appropriate treatment optimization and transitioning in the management of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2014;28(4):438-453. http://dx.doi.org/10.1111/jdv.12118

13Tsai YC, Tsai TF. Switching biologics in psoriasis - practical guidance and evidence to support. Expert Rev Clin Pharmacol. 2020;13(5):493-503. http://dx.doi.org/10.1080/17512433.2020.1767590

14Cohen M, Maillart E, Tourbah A, et al. Switching from natalizumab to fingolimod in multiple sclerosis: a French prospective study. JAMA Neurol. 2014;71(4):436-441. http://dx.doi.org/10.1001/jamaneurol.2013.6240

15Kappos L, Radue EW, Comi G, et al. Switching from natalizumab to fingolimod: a randomized, placebo-controlled study in RRMS. Neurology. 2015;85(1):29-39. http://dx.doi.org/10.1212/wnl.0000000000001706

16Furst DE, Keystone EC, Fleischmann R, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis. 2010;69(Suppl 1):i2-i29. http://dx.doi.org/10.1136/ard.2009.123885

17Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784. http://dx.doi.org/10.1002/art.23721

18Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977. http://dx.doi.org/10.1136/annrheumdis-2016-210715

19Kerschbaumer A, Sepriano A, Smolen JS, et al. Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):744-759. http://dx.doi.org/10.1136/annrheumdis-2019-216656

20Smolen JS, Burmester GR, Combe B, et al. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study. Lancet. 2016;388(10061):2763-2774. http://dx.doi.org/10.1016/s0140-6736(16)31651-8

21Schiff M, Pritchard C, Huffstutter JE, et al. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis. 2009;68(11):1708-1714. http://dx.doi.org/10.1136/ard.2008.099218

22Bykerk VP, Ostor AJ, Alvaro-Gracia J, et al. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Ann Rheum Dis. 2012;71(12):1950-1954. http://dx.doi.org/10.1136/annrheumdis-2011-201087

Glossary

CGRP = calcitonin gene-related peptide

mAb = monoclonal antibody

Appendix: Efficacy and Safety of Switching From Biologics in Other Disease States

The following information while not specific to CGRP mAbs may be of assistance as a reference point to inform your independent clinical judgment.

Switching Biologics in Psoriasis

Consensus regarding treatment optimization and transitioning for moderate-to-severe plaque psoriasis suggests that switching from one biologic therapy to another

  • includes the use of a washout period if the switch is made due to an adverse event, and
  • does not include a washout period if the switch is made due to a lack of efficacy.12,13 

Switching Biologics in Multiple Sclerosis

Studies involving transitioning between biologics for multiple sclerosis suggest that the washout out period between mAbs be

  • no longer than necessary, and
  • less than 3 months.14,15

This is to balance concerns over multiple antibodies being present with concerns over elevated disease activity and subsequent patient impairment resulting from an extended washout period.14,15 

Switching Biologics in Rheumatoid Arthritis

For those diseases such as rheumatoid arthritis where mAbs have been available for an extended period of time, the safety and efficacy of switching due to tolerability or efficacy among biologics in the same class are well-established.16-19  

A series of trials in patients with rheumatoid arthritis ranging from 6 months to 2 years in length suggests a similar safety profile when switching occurs with or without a washout period.20-22

Fecha de la última revisión: 2020 M11 18


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