Emgality ® ▼ (galcanezumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Was alopecia reported in Emgality® ▼ (galcanezumab) clinical trials?

Treatment-emergent alopecia was reported in <1% of patients treated with galcanezumab in phase 3, double-blind, placebo-controlled trials. Events were mild or moderate in severity, and no galcanezumab-treated patients discontinued due to alopecia.

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Additional Information

Galcanezumab has been studied in migraine prevention.1-4 A brief overview of the phase 3 double-blind, placebo-controlled studies is provided in the Overview of Phase 3 Migraine Studies. Treatment-emergent adverse events related to alopecia are summarized below.

Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Additional information on alopecia can be found in the Additional Published Information on Alopecia.

Incidence and Characterization of Treatment-Emergent Alopecia in the Phase 3 Migraine Prevention Studies

The incidence and severity of alopecia during the double-blind treatment phase of EVOLVE-1, EVOLVE-2, and REGAIN for migraine prevention are summarized in Incidence and Severity of Treatment-Emergent Alopecia Events in EVOLVE-1, EVOLVE-2, and REGAIN Studies: Double-Blind Treatment Phase.

The alopecia events were mild or moderate in severity, with no severe events reported. One placebo-treated patient from the REGAIN study discontinued due to treatment-emergent alopecia.5


Incidence and Severity of Treatment-Emergent Alopecia Events in EVOLVE-1, EVOLVE-2, and REGAIN Studies: Double-Blind Treatment Phase5

TEAE

PBO
N=1451
n (%)

GMB 120 mg
N=705
n (%)

GMB 240 mg
N=730
n (%)

Alopecia

Incidence

5 (0.3)

3 (0.4)

4 (0.6)

Severity 

Mild

4 (0.3)

3 (0.4)

3 (0.4)

Moderate

1 (0.1)

0 (0.0)

1 (0.1)

Severe

0 (0.0)

0 (0.0)

0 (0.0)

Alopecia areata

Incidence

0 (0.0)

1 (0.1)

0 (0.0)

Severity

Mild

0 (0.0)

1 (0.1)

0 (0.0)

Moderate

0 (0.0)

0 (0.0)

0 (0.0)

Severe

0 (0.0)

0 (0.0)

0 (0.0)

Abbreviations: GMB = galcanezumab; PBO = placebo; TEAE = treatment-emergent adverse event.

No patients in the CONQUER study experienced treatment-emergent alopecia during double-blind treatment.5

Postmarketing Spontaneous Reports

Based on postmarketing spontaneous reports from the Eli Lilly and Company spontaneous adverse event (AE) database received through March 27, 2022,

  • alopecia has been rarely reported (≥0.01% and <0.1%), and
  • alopecia areata and androgenetic alopecia have been very rarely reported (<0.01%).5

Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an event.6

Spontaneous reporting has limited use due to

  • lack of control population
  • underreporting or reporting bias, and
  • missing or incomplete information regarding medical history or concomitant medications.6

Biological Plausibility

There are conflicting reports of the role of calcitonin gene-related peptide (CGRP) on hair growth in the published literature.7-10

Calcitonin-gene related peptide

  • has been shown to interact with peptides that control hair growth7-10
  • has immunomodulatory properties8
  • might be an important regulatory factor for maintenance and restoration of immune privilege at the proximal epithelium of hair follicles11
  • suppresses antigen presentation to lymphocytes and slows down their proliferation and reactivity, and8
  • expression decreases in alopecia areata lesions.11

Therefore, modulating CGRP function may have potential impact on the hair follicle. A further discussion of this topic is provided below Additional Published Information on Alopecia. 

References

1Skljarevski 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

2Stauffer 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

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.

6Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-C44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6

7Kinori M, Bertolini M, Funk W, et al. Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-gamma-induced collapse of human hair follicle immune privilege. Exp Dermatol. 2012;21(3):223-226. http://dx.doi.org/10.1111/j.1600-0625.2011.01432.x

8Pi L-Q, Jin X-H, Hwang ST, et al. Effects of calcitonin gene-related peptide on the immune privilege of human hair follicles. Neuropeptides. 2013;47(1):51-57. http://dx.doi.org/10.1016/j.npep.2012.07.008

9Samuelov L, Kinori M, Bertolini M, et al. Neural controls of human hair growth: calcitonin gene-related peptide (CGRP) induces catagen. J Dermatol Sci. 2012;67(2):153-155. http://dx.doi.org/10.1016/j.jdermsci.2012.04.006

10Suh DH, Eun HC. The effect of calcitonin gene-related peptide on hair growth in vitro. Ann Dermatol. 1995;7(4):308-312. https://doi.org/10.5021/ad.1995.7.4.308

11Paus R, Ito N, Takigawa M, Ito T. The hair follicle and immune privilege. J Investig Dermatol Symp Proc. 2003;8(2):188-194. http://dx.doi.org/10.1046/j.1087-0024.2003.00807.x

12Blume-Peytavi U, Blumeyer A, Tosti A, et al. S1 guideline for diagnostic evaluation in androgenetic alopecia in men, women and adolescents. Br J Dermatol. 2011;164(1):5-15. http://dx.doi.org/10.1111/j.1365-2133.2010.10011.x

13Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol. 2001;144(22):297–304. http://dx.doi.org/10.1046/j.1365-2133.2001.04018.x

14Norwood OT. Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg. 2001;27(1):53–54. https://www.ncbi.nlm.nih.gov/pubmed/11231244

15Varothai S, Bergfeld WF. Androgenetic alopecia: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):217-230. http://dx.doi.org/10.1007/s40257-014-0077-5

16Gan DCC, Sinclair RD. Prevalence of male and female pattern hair loss in Maryborough. J Investig Dermatol Symp Proc. 2005;10(3):184–189. https://doi.org/10.1111/j.1087-0024.2005.10102.x

17Olsen EA, Messenger AG, Shapiro J, et al. Evaluation and treatment of male and female pattern hair loss. J Am Acad Dermatol. 2005;52(2):301–311. https://doi.org/10.1016/j.jaad.2004.04.008

18Hamilton JB. Patterned loss of hair in man: types and incidence. Ann N Y Acad Sci. 1951;53(3):708–728. http://dx.doi.org/10.1111/j.1749-6632.1951.tb31971.x

19Alonso L, Fuchs E. The hair cycle. J Cell Sci. 119:391-393. http://dx.doi.org/10.1242/jcs02793

20Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev. 2001;81(1):449-494. http://dx.doi.org/10.1152/physrev.2001.81.1.449

21Cristoph T, Müller-Röver S, Audring H, et al. The human hair follicle immune system: cellular composition and immune privilege. Br J Dermatol. 2000;142(5):862-873. https://doi.org/10.1046/j.1365-2133.2000.03464.x

Appendix

Additional Published Information on Alopecia

Alopecia is more common in women than men, and its prevalence increases with age.12 In the United Kingdom and United States, the prevalence of alopecia is

  • 3% to 6% in women <30 years of age, and
  • 29% to 42% in women ≥70 years of age.12-14

The prevalence of alopecia also increases with age in men, affecting more than 80% of Caucasian men ≥70 years of age.12,15-18

The hair follicle is a unique organ in the body that undergoes cycles of

  • hair production (anagen)
  • apoptosis-mediated regression (catagen), and
  • relative quiescence (telogen).19

This cyclical process is complex and regulated by several factors, including sensory neurons.20 Sensory neurons release CGRP, which has been shown to be an important regulatory factor in hair growth.8

The proximal epithelium of anagen hair follicles are known to be an area of immune privilege.21 Immune privilege, is characterized by a low level of expression of major histocompatibility complex (MHC) class I antigens. The function of MHC is to present antigens to T-cells and if present on the hair bulb cells, they may facilitate damage to the hair follicle by the T-cells.8

Immune privilege at the anagen hair follicles is generated and maintained by a number of mechanisms, including 

  • local production of immunosuppressive agents, and
  • decreased MHC expression.11

CGRP might be an important regulatory factor for maintenance and restoration of immune privilege via suppression of MHC class I antigen, which in turn could protect proximal hair follicles from autoreactive cluster of differentiation 8 T-cell attack.11

Overview of Phase 3 Migraine Studies

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 randomized to either placebo or treatment in a

  • 2:1:1 ratio in the EVOLVE-1, EVOLVE-2, REGAIN studies,1-3 and
  • 1:1 ratio in the CONQUER study.4

The galcanezumab doses used and duration of the phase 3, double-blind, placebo-controlled migraine prevention studies are summarized in Summary of Phase 3, Double-Blind, Placebo-Controlled Galcanezumab Migraine Prevention Studies.


Summary of Phase 3, Double-Blind, Placebo-Controlled Galcanezumab Migraine Prevention Studies

Study Name

Treatments

Study Duration

EVOLVE-12
N=858
EVOLVE-21
N=915

PBO, GMB 120 mg,a
or
240 mg SQ monthly

6 months double-blind

REGAIN3
N=1,113

PBO, GMB 120 mg monthly,a
or
240 mg SQ monthly

3 months double-blind,
with optional 9-month open-label extension

CONQUER4
N=462

PBO or GMB 120 mg SQ monthlya

3 months double-blind, 
with optional 3-month open-label extension

Abbreviations: GMB = galcanezumab, PBO = placebo; SQ = subcutaneous.

aThe initial dose was administered as a 240-mg loading dose, followed by subsequent monthly doses of 120 mg.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: 22 June 2022


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