Emgality® ▼ (galcanezumab): Treatment Emergent Alopecia

Additional Information

Galcanezumab has been studied in migraine prevention.^1-3 A brief overview of the phase 3 double-blind, placebo controlled studies is provided in: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.

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 the phase 3 double-blind, placebo-controlled galcanezumab studies for migraine prevention are summarized in Table 1.

The alopecia events were mild or moderate in severity, with no severe events reported. One placebo-treated patient discontinued due to treatment-emergent alopecia.⁴

Table 1. Incidence and Severity of Treatment-Emergent Alopecia Events in Phase 3 Migraine Prevention Studies: Double-Blind Treatment Phase⁴

	PBO N=1451 n (%)	GMB 120 mg N=705 n (%)	GMB 240 mg N=730 n (%)
Alopecia	5 (0.3)	3 (0.4)	4 (0.6)
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	0 (0.0)	1 (0.1)	0 (0.0)
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.

Biological Plausibility

There are conflicting reports of the role of CGRP on hair growth in the published literature.^5-8

Calcitonin-gene related peptide

• has been shown to interact with peptides that control hair growth^5-8

• has immunomodulatory properties⁶

• might be an important regulatory factor for maintenance and restoration of immune privilege at the proximal epithelium of hair follicles⁹

• suppresses antigen presentation to lymphocytes and slows down their proliferation and reactivity, and⁶

• expression decreases in alopecia areata lesions.⁹

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

References

1. Skljarevski 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

2. Stauffer 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

3. Detke 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

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

5. Kinori 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

6. Pi 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

7. Samuelov 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

8. Suh 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

9. Paus 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

10. Blume-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

11. Birch 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

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

13. Varothai 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

14. Gan 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

15. Olsen 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

16. Hamilton 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

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

18. Stenn 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

19. Cristoph 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

Glossary

CD8 = cluster of differentiation 8

CGRP = calcitonin gene-related peptide

MHC = major histocompatibility complex

Appendix

Additional Published Information: Alopecia

Alopecia is more common in women than men, and its prevalence increases with age.¹⁰ 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.^10-12

The prevalence of alopecia also increases with age in men, affecting more than 80% of Caucasian men ≥70 years of age.^10,13-16

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).¹⁷

This cyclical process is complex and regulated by several factors, including sensory neurons.¹⁸ Sensory neurons release CGRP, which has been shown to be an important regulatory factor in hair growth.⁶

The proximal epithelium of anagen hair follicles are known to be an area of immune privilege.¹⁹ Immune privilege, is characterized by a low level of expression of MHC class Ia antigens. The function of MHC is to present antigens to T-cells⁶ and if present on the hair bulb cells, they may facilitate damage to the hair follicle by the T-cells. 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.⁹ Calcitonin-gene related peptide 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 CD8+ T-cell attack.⁹

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 and

• chronic migraine (REGAIN).³

The studies had a duration of

• 6 months for prevention of episodic migraine,^1,2 and

• 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.³ 

Patients were randomized at the beginning of double-blind treatment in a 2:1:1 ratio to receive monthly subcutaneous injections of 

• placebo

• galcanezumab 120 mg with a loading dose of 240 mg, or

• galcanezumab 240 mg.^1-3 

▼ 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.