Table 1.
Current therapeutic pipeline for atopic dermatitis
| Strategy | Drug type and mode of application | Agent/company | Mode of action/target | Clinical development phase in atopic dermatitis | Clinical trial ID |
|---|---|---|---|---|---|
| Modulating the microbiome | Bacterial strains — topical | B244 (AOBiome) | Nitric oxide donor | IIb | NCT04490109 |
| ShA9 (NIAID) | Targeted microbiome transplant | I/IIa | NCT03151148 | ||
| FB-401 (Forte Biosciences) | Bacterial replacement, anti-inflammation via TLR5 and TNFR activation | IIb | NCT04504279 | ||
| Small molecule — topical | CLS-001/omiganan (Cutaneous Life Sciences) | Cell membrane enhancer | II | NCT02456480 | |
| ATx201/niclosamide (Union Therapeutics) | Protonophore activity | II | NCT04339985 | ||
| Bacterial strains — oral | EDP1815 (Evelo) | Modulation of systemic inflammation | Ib | NCT03733353 | |
| STMC-103H (Siolta therapeutics) | Immunomodulation via microbiome manipulation | Ib | NCT03819881 | ||
| Targeting the innate immune response | Small molecule — topical | Tapinarof/benvitimod (Dermavant) | AhR agonist | IIb | NA |
| Biologic — injection | Tezepelumab (Amgen/AstraZeneca) | TSLP | IIa | NCT02525094 | |
| Etokimab (AnaptysBio) | IL-33 | IIa | NCT03533751 | ||
| REGN3500 (Regeneron) | IL-33 | IIa | NCT03738423 | ||
| Astegolimab (Genentech) | IL-33 | IIa | NCT03747575 | ||
| MEDI3506 (MedImmune) | IL-33 | IIa | NCT04212169 | ||
| Bermekimab (Janssen) | IL-1α | IIa | NCT03496974 | ||
| Spesolimab (Böhringer Ingelheim) | IL-36R | IIa | NCT03822832 | ||
| Targeting the adaptive immune response | Biologic — injection | GBR 830/ISB 830 (Glenmark/Ichnos) | OX40 | IIb | NCT03568162 |
| KHK4083 (Kyrin) | OX40 | IIb | NCT03703102 | ||
| KY1005 (Kymab/Sanofi) | OX40L | IIa | NCT03754309 | ||
| Dupilumab (Regeneron/Sanofi) | IL-4Rα | Approved globally, staggered paediatric programme ongoing | NCT03346434 | ||
| CBP-201 (Connect Biopharma) | IL-4Rα | IIb | NCT04444752 | ||
| AK120 (Akesobio) | IL-4Rα | Ib | NCT04256174 | ||
| ASLAN004 (ASLAN) | IL-13Rα1 | Ib | NCT04090229 | ||
| Tralokinumab (LEO Pharma) | IL-13 | Approved in EU, staggered paediatric programme ongoing | NCT03526861 | ||
| Lebrikizumab (Allmiral/Lilly) | IL-13 | III, staggered paediatric programme ongoing | NCT04250350 | ||
| Benralizumab (AstraZeneca) | IL-5Rα | II | NCT04605094 | ||
| Omalizumab (Novartis) | IgE | II | NCT02300701 | ||
| FB825/anti-CεmX (LEO Pharma/Oneness Biotech) | mIgE | IIa | NCT04413942 | ||
| Fezakinumab (IIT) | IL-22 | IIa | NCT01941537 | ||
| LEO 138559 (LEO Pharma) | IL-22R1 | Ib | NCT03514511 | ||
| Secukinumab (Novartis) | IL-17A | IIa | NCT02594098, NCT03568136 | ||
| Risankizumab (AbbVie) | IL-23 | IIa | NCT03706040 | ||
| LY3471851 (Lilly) | rhIL-2 to Treg cells | Ib | NCT04081350 | ||
| Small molecule — oral | Adriforant (Novartis) | H4R | IIb | NCT03517566 | |
| LEO 152020/JW1601 (LEO Pharma) | H4R | I | NCT04203836 | ||
| RPT193 (RAPT Therapeutics) | CCR4 | IIa | NCT04271514 | ||
| Etrasimod (Arena Pharma) | S1PR1, S1PR4, S1PR5 | IIb | NCT04162769 | ||
| SCD-044 (Sun Pharma) | S1PR1 | IIa | NCT04684485 | ||
| LC51-0255 (LG Chem) | S1PR1 | I | NA | ||
| BMS-986166 (Bristol Myers Squibb) | S1PR1 | IIa | NCT03038711 | ||
| KT-474 (Kymera) | S1PR1 | Ib | NCT04772885 | ||
| Small molecule — topical | AKP-19 (Akaal Pharma) | S1PR1 | II | NA | |
| Lotamilast (RVT-501 /E6005) (Dermavant) | PDE4 | II | NCT03394677, NCT02950922 | ||
| Difamilast (OPA-15406/MM36) (Otsuka) | PDE4 | II | NCT02945657 | ||
| DRM02 (Dermira) | PDE4 | II | NCT01993420 | ||
| LEO 29102 (LEO Pharma) | PDE4 | II | NCT01037881 | ||
| Roflumilast (AstraZeneca) | PDE4 | II; pharmacokinetics and efficacy in paediatrics | NCT04156191 | ||
| Hemay-808 (Tianjin Hemay Pharmaceutical) | PDE4 | II | NCT04352595 | ||
| PF-07038124 (Pfizer) | PDE4 | II | NCT04664153 | ||
| BEN2293 (BenevolentiAI) | TRK | I/II | NCT04737304 | ||
| HY209 (Shaperon) | GPCR19 | IIa | NCT04530643 | ||
| VTP-38543 (Vitae Pharma) | Liver X receptor-β | I/II | NCT02655679 | ||
| ALX 101 (Ralexar) | Liver X receptor | II | NCT03859986 | ||
| Targeting itching | Biologic — injection | Nemolizumab (Galderma) | IL-31 | III | NCT03989349, NCT03985943 |
| Vixarelimab (Kiniksa Pharma) | OSMRβ | IIa/b | NCT03816891 | ||
| Small molecule — oral | Serlopitant (Menlo) | NK1R | II | NCT02975206 | |
| Tradipitant (Vanda) | NK1R | II | NCT03568331 | ||
| BLU-5937 (Bellus) | P2X3 | II | NCT04693195 | ||
| Inhibiting Janus kinases | Small molecule — topical | Delgocitinib (Japan Tobacco/LEO) | Pan-JAK | IIb in EU, approved in Japan | NCT03725722 |
| Ruxolitinib (Incyte) | JAK1/JAK2 | III | NCT03745638, NCT03745651 | ||
| Cerdulatinib (RVT/DMVT502) (Dermavant) | Pan-JAK/SYK | Ib | NA | ||
| Brepocitinib (Pfizer) | JAK1/TYK2 | IIb | NCT03903822 | ||
| ATI-1777 (Aclaris) | JAK1/JAK3 | II | NCT04598269 | ||
| CEE321 (Novartis) | Pan-JAK | I | NCT04612062 | ||
| Jaktinib (Suzhou Zeigen Biopharma) | Pan-JAK | IIa | NCT04539639 | ||
| SHR0302 (Reistone Biopharma) | JAK1 | II | NCT04717310 | ||
| Small molecule — oral | Baricitinib (Lilly) | JAK1/JAK2 | Approved in EU for adults, staggered paediatric programme ongoing | NCT03952559 | |
| Upadacitinib (AbbVie) | JAK1 | III, staggered paediatric programme ongoing | NCT03646604 | ||
| Abrocitinib (Pfizer) | JAK1 | III, staggered paediatric programme ongoing | NCT03627767 | ||
| SHR0302 (Reistone Biopharma) | JAK1 | II | NCT04162899 |
AhR, aryl-hydrocarbon receptor; BTK, Bruton tyrosine kinase; CCR4, C-C chemokine receptor 4; GPCR19, G protein-coupled receptor 19; H4R, type 4 histamine receptor; IL-4Rα, α-chain of the IL-4 receptor; IL-5Rα, α-chain of the IL-5 receptor; IL-13Rα1, α1 chain of the IL-13 receptor; IL-22R1, IL-22 receptor 1; JAK, Janus kinase; NK1R, neurokinin 1 receptor; NA, not applicable; OSMRβ, oncostatin M receptor-β; OX40L, OX40 ligand; PDE4, phosphodiesterase 4; P2X3, purinoreceptor 3; rhIL-2, recombinant human IL-2; S1PR1, sphingosine 1-phosphate receptor 1; Treg cell, regulatory T cell; TRK, tropomyosin receptor kinase; TSLP, thymic stromal lymphopoietin.