Advertisement

New Drugs for Alopecias

  • Jacob GriggsEmail author
  • Rodrigo Pirmez
  • Antonella Tosti
Chapter

Abstract

The new drugs in the development of AGA include PGF2 analogs, a PGD2 receptor antagonist, Wnt pathway activators, an androgen receptor antagonist, a topical JAK inhibitors, and topical finasteride. While many of these have already shown efficacy compared to placebo, none have shown superiority to topical minoxidil; however, they may still have future as an adjuvant treatment with topical minoxidil. For AA, oral JAK inhibitors are a promising new development, although other new drugs are in development as well. A particularly interesting one is BNZ-1, which has the potential to suppress the autoimmune response without causing systemic immunosuppression.

Keywords

Alopecia Alopecia areata Androgenetic alopecia Bricitinib Bimatoprost BNZ-1 JAK inhibitors Latanoprost Ruxolitinib Setipiprant Tofacitinib 

References

  1. 1.
    Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57(1):9–17.  https://doi.org/10.1007/s12020-017-1280-y.CrossRefPubMedGoogle Scholar
  2. 2.
    Blumeyer A, Tosti A, Messenger A, Reygagne P, Del Marmol V, Spuls PI, et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. J Dtsch Dermatol Ges. 2011;9:S1–S57.  https://doi.org/10.1111/j.1610-0379.2011.07802.x.CrossRefPubMedGoogle Scholar
  3. 3.
    Jaworsky C, Kligman AM, Murphy GF. Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. Br J Dermatol. 1992;127(3):239–46. http://www.ncbi.nlm.nih.gov/pubmed/1390168. Accessed 3 Nov 2018.CrossRefGoogle Scholar
  4. 4.
    Law SK. Bimatoprost in the treatment of eyelash hypotrichosis. Clin Ophthalmol. 2010;4:349–58. http://www.ncbi.nlm.nih.gov/pubmed/20463804. Accessed 3 Nov 2018.CrossRefGoogle Scholar
  5. 5.
    Blume-Peytavi U, Lönnfors S, Hillmann K, Garcia Bartels N. A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia. J Am Acad Dermatol. 2012;66(5):794–800.  https://doi.org/10.1016/j.jaad.2011.05.026.CrossRefGoogle Scholar
  6. 6.
    Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv Ophthalmol. 2002;47(Suppl 1):S185–202. http://www.ncbi.nlm.nih.gov/pubmed/12204716. Accessed 29 Nov 2018.CrossRefGoogle Scholar
  7. 7.
    Duke University. Topical Bimatoprost effect on androgen dependent hair follicles. In: ClinicalTrials.gov. Bethesda: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/NCT01325350 NLM Identifier: NCT01325350. Accessed 3 Nov 2018.Google Scholar
  8. 8.
    Allergan. Safety and efficacy study of Bimatoprost in the treatment of men with Androgenic Alopecia. In: ClinicalTrials.gov. Bethesda: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/results/NCT01325337 NLM Identifier: NCT01325337. Accessed 3 Nov 2018.Google Scholar
  9. 9.
    Allergan A. Safety and efficacy study of Bimatoprost in men with Androgenic Alopecia (AGA). In: ClinicalTrials.gov. Bethesda: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/results/NCT01904721 NLM Identifier: NCT01904721. Accessed 3 Nov 2018.Google Scholar
  10. 10.
    Allergan. Safety and efficacy study of Bimatoprost in the treatment of women with female pattern hair loss. In: ClinicalTrials.gov. Bethesda: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/results/NCT01325350 NLM Identifier: NCT01325350. Accessed 3 Nov 2018.Google Scholar
  11. 11.
    Talavera-Adame D, Newman D, Newman N. Conventional and novel stem cell based therapies for androgenic alopecia. Stem Cells Cloning. 2017;10:11–9.  https://doi.org/10.2147/SCCAA.S138150.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012;4(126):126ra34.  https://doi.org/10.1126/scitranslmed.3003122.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ratner P, Andrews CP, Hampel FC, Martin B, Mohar DE, Bourrelly D, et al. Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from phase 2 and phase 3 randomized, double-blind, placebo- and active-referenced studies. Allergy, Asthma Clin Immunol. 2017;13(1):18.  https://doi.org/10.1186/s13223-017-0183-z.CrossRefGoogle Scholar
  14. 14.
    Premanand A, Reena Rajkumari B. Androgen modulation of Wnt/β-catenin signaling in androgenetic alopecia. Arch Dermatol Res. 2018;310(5):391–9.  https://doi.org/10.1007/s00403-018-1826-8.CrossRefPubMedGoogle Scholar
  15. 15.
    Samumed. Monthly Newsletter, August 2018. https://www.samumed.com/medium/image/monthly-newsletter-2018-7_387/view.aspx. Accessed 2 Nov 2018.
  16. 16.
    Yazici Y, Swearingen CJ, Simsek I, DiFrancesco A, Hood JD. Safety, tolerability and efficacy of a topical treatment (SM04554) for Androgenetic Alopecia (AGA): results from a phase 2 trial. In: Poster session presented at: American Academy of Dermatology (AAD). Washington, D.C; 2016 March 04-08.Google Scholar
  17. 17.
    Seykora J, Simsek I, DiFrancesco A, Swearingen C, Yazici Y. Safety and biopsy outcomes of a topical treatment (SM04554) for Male Androgenetic Alopecia (AGA): results from a phase 2, multicenter, randomized, double-blind, vehicle-controlled trial. In: Poster session presented at: American Academy of Dermatology (AAD). Orlando; 2017 March 03-07.Google Scholar
  18. 18.
    Cassiopea. Creating Innovation in Dermatology. In: Presented at: Jefferies global health care conference; 2016 June 9; New York. http://www.cassiopea.com/~/media/Files/C/Cassiopea/presentations/Jefferies_GHCC_Jun2016.pdf.
  19. 19.
  20. 20.
    Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, et al. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015;1(9):e1500973.  https://doi.org/10.1126/sciadv.1500973.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol. 2017;76(1):22–8.  https://doi.org/10.1016/j.jaad.2016.09.007.CrossRefPubMedGoogle Scholar
  22. 22.
    Caserini M, Radicioni M, Leuratti C, Terragni E, Iorizzo M, Palmieri R. Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia. Int J Clin Pharmacol Ther. 2016;54(1):19–27.  https://doi.org/10.5414/CP202467.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol. 2018;78(1):1–12.  https://doi.org/10.1016/j.jaad.2017.04.1141.CrossRefPubMedGoogle Scholar
  24. 24.
    Messenger AG, McKillop J, Farrant P, McDonagh AJ, Sladden M. British Association of Dermatologists’ guidelines for the management of alopecia areata 2012. Br J Dermatol. 2012;166(5):916–26.  https://doi.org/10.1111/j.1365-2133.2012.10955.x.CrossRefPubMedGoogle Scholar
  25. 25.
    Damsky W, King BA. JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736–44.  https://doi.org/10.1016/j.jaad.2016.12.005.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Renert-Yuval Y, Guttman-Yassky E. The changing landscape of Alopecia Areata: the therapeutic paradigm. Adv Ther. 2017;34(7):1594–609.  https://doi.org/10.1007/s12325-017-0542-7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014;20(9):1043–9.  https://doi.org/10.1038/nm.3645.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ghoreschi K, Gadina M. Jakpot! New small molecules in autoimmune and inflammatory diseases. Exp Dermatol. 2014;23(1):7–11.  https://doi.org/10.1111/exd.12265.CrossRefPubMedGoogle Scholar
  29. 29.
    Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1(15):e89790.  https://doi.org/10.1172/jci.insight.89790.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776.  https://doi.org/10.1172/jci.insight.89776.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Jabbari A, Sansaricq F, Cerise J, Chen JC, Bitterman A, Ulerio G, et al. An open-label pilot study to evaluate the efficacy of Tofacitinib in moderate to severe patch-type Alopecia Areata, Totalis, and Universalis. J Invest Dermatol. 2018;138(7):1539–45.  https://doi.org/10.1016/j.jid.2018.01.032.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Olsen E, Hordinsky M, McDonald-Hull S, Price V, Roberts J, Shapiro J, et al. Alopecia areata investigational assessment guidelines. National Alopecia Areata Foundation. J Am Acad Dermatol. 1999;40(2):242–6.  https://doi.org/10.1016/S0190-9622(99)70195-7.CrossRefPubMedGoogle Scholar
  33. 33.
    Almohanna HM, Perper M, Tosti A. Safety concerns when using novel medications to treat alopecia. Expert Opin Drug Saf. 2018;17(11):1115–28.  https://doi.org/10.1080/14740338.2018.1533549.CrossRefPubMedGoogle Scholar
  34. 34.
    Papp KA, Krueger JG, Feldman SR, Langley RG, Thaci D, Torii H, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol. 2016;74(5):841–50.  https://doi.org/10.1016/j.jaad.2016.01.013.CrossRefPubMedGoogle Scholar
  35. 35.
    Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75(5):831–41.  https://doi.org/10.1136/annrheumdis-2014-205847.CrossRefPubMedGoogle Scholar
  36. 36.
    Yamanaka H, Tanaka Y, Takeuchi T, Sugiyama N, Yuasa H, Toyoizumi S, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18(1):34.  https://doi.org/10.1186/s13075-016-0932-2.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Bayart CB, DeNiro KL, Brichta L, Craiglow BG, Sidbury R. Topical Janus kinase inhibitors for the treatment of pediatric alopecia areata. J Am Acad Dermatol. 2017;77(1):167–70.  https://doi.org/10.1016/j.jaad.2017.03.024.CrossRefGoogle Scholar
  38. 38.
    Ocampo-Garza J, Griggs J, Tosti A. New drugs under investigation for the treatment of alopecias. Expert Opin Investig Drugs. 2019. In Press;  https://doi.org/10.1080/13543784.2019.1568989.CrossRefGoogle Scholar
  39. 39.
    Happle R, Hausen BM, Wiesner-Menzel L. Diphencyprone in the treatment of alopecia areata. Acta Derm Venereol. 1983;63(1):49–52. http://www.ncbi.nlm.nih.gov/pubmed/6191489. Accessed 3 Nov 2018.PubMedGoogle Scholar
  40. 40.
    Lamb RC, Young D, Holmes S. Retrospective review of diphencyprone in the treatment of alopecia areata. Clin Exp Dermatol. 2016;41(4):352–8.  https://doi.org/10.1111/ced.12776.CrossRefPubMedGoogle Scholar
  41. 41.
    Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med. 2012;366(16):1515–25.  https://doi.org/10.1056/NEJMra1103442.CrossRefPubMedGoogle Scholar
  42. 42.
    Katikaneni R, Seymour AW, Gulati R, Ponnapakkam T, Gensure RC. Therapy for Alopecia Areata in mice by stimulating the hair cycle with parathyroid hormone agonists linked to a collagen-binding domain. J Investig Dermatol Symp Proc. 2015;17(2):13–5.  https://doi.org/10.1038/jidsymp.2015.32.CrossRefPubMedGoogle Scholar
  43. 43.
    Venten I, Hess N, Hirschmüller A, Altmeyer P, Brockmeyer N. Treatment of therapy-resistant Alopecia areata with fumaric acid esters. Eur J Med Res. 2006;11(7):300–5. http://www.ncbi.nlm.nih.gov/pubmed/16899425. Accessed 3 Nov 2018.PubMedGoogle Scholar
  44. 44.
    Ursini F, Russo E, De Giorgio R, De Sarro G, D’Angelo S. Current treatment options for psoriatic arthritis: spotlight on abatacept. Ther Clin Risk Manag. 2018;14:1053–9.  https://doi.org/10.2147/TCRM.S148586.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Blair HA, Deeks ED. Abatacept: a review in rheumatoid arthritis. Drugs. 2017;77(11):1221–33.  https://doi.org/10.1007/s40265-017-0775-4.CrossRefPubMedGoogle Scholar
  46. 46.
    Magdaleno-Tapial J, Valenzuela-Oñate C, Sánchez-Carazo JL, Alegre-de Miquel V. Improvement of alopecia areata with apremilast. Australas J Dermatol. 2018;  https://doi.org/10.1111/ajd.12934.CrossRefGoogle Scholar
  47. 47.
    Keren A, Shemer A, Ullmann Y, Paus R, Gilhar A. The PDE4 inhibitor, apremilast, suppresses experimentally induced alopecia areata in human skin in vivo. J Dermatol Sci. 2015;77(1):74–6.  https://doi.org/10.1016/j.jdermsci.2014.11.009.CrossRefPubMedGoogle Scholar
  48. 48.
    Liu LY, King BA. Lack of efficacy of apremilast in 9 patients with severe alopecia areata. J Am Acad Dermatol. 2017;77(4):773–4.  https://doi.org/10.1016/j.jaad.2017.05.034.CrossRefPubMedGoogle Scholar
  49. 49.
    Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe Atopic Dermatitis. N Engl J Med. 2014;371(2):130–9.  https://doi.org/10.1056/NEJMoa1314768.CrossRefPubMedGoogle Scholar
  50. 50.
    Penzi LR, Yasuda M, Manatis-Lornell A, Hagigeorges D, Senna MM. Hair regrowth in a patient with long-standing Alopecia Totalis and Atopic Dermatitis treated with Dupilumab. JAMA Dermatol. 2018;  https://doi.org/10.1001/jamadermatol.2018.2976.CrossRefGoogle Scholar
  51. 51.
    Mitchell K, Levitt J. Alopecia areata after dupilumab for atopic dermatitis. JAAD Case Rep. 2018;4(2):143–4.  https://doi.org/10.1016/j.jdcr.2017.11.020.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Iftikhar IH, Schimmel M, Bender W, Swenson C, Amrol D. Comparative efficacy of Anti IL-4, IL-5 and IL-13 drugs for treatment of eosinophilic asthma: a network meta-analysis. Lung. 2018;196(5):517–30.  https://doi.org/10.1007/s00408-018-0151-5.CrossRefPubMedGoogle Scholar
  53. 53.
    Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an Anti–IL-13 mAb. J Allergy Clin Immunol. 2018;  https://doi.org/10.1016/j.jaci.2018.05.029.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Dr. Phillip Frost Department of Dermatology and Cutaneous SurgeryUniversity of Miami, Leonard M. Miller School of MedicineMiamiUSA
  2. 2.Department of Dermatology Santa Casa da MisericordiaRio De JaneiroBrazil
  3. 3.Fredric Brandt Endowed Professor of Dermatology, Dr. Phillip Frost Department of Dermatology and Cutaneous SurgeryUniversity of Miami Miller School of MedicineMiamiUSA

Personalised recommendations