Table 2.
Emerging systemic treatments for HS
| Drug name (MOA) | Author or clinical trial # | Study type | Study goal and primary endpoint(s) | Patients enrolled | (Anticipated) Completion date | Results or recruitment status |
|---|---|---|---|---|---|---|
| MSB11022 (adalimumab biosimilar/TNF-α antagonist), SQ | Sabet et al. 2022 [23] | Phase 1 randomized, open-label, parallel-group |
Evaluate PK, safety, and tolerability Endpoints: Cmax), AUC0–t, and AUC0–∞ |
216 | March 2020 | Delivery via AI or PFS was comparable in terms of PK |
| Remsima (infliximab biosimilar/TNF-α antagonist), SQ | NCT05663268 | Phase 1 open-label |
Assess efficacy and safety in patients with resistant HS Endpoints: HiSCR, HS-PGA, and DLQI after 14 weeks |
16 | September 2023 | Active, not recruiting |
| Bermekimab (MABp1, IL-1α inhibitor), SQ | Gottlieb et al. 2020 [43] | Phase 2 open-label |
Evaluate safety, tolerability, and efficacy in patients with moderate-to-severe HS who had either failed initial treatment with anti-TNF agents or never received anti-TNF treatment Endpoint: number with adverse events up to day 93 |
42 | January 2019 | 61% and 63% of anti-TNF naïve and anti-TNF failure groups, respectively, achieved HiSCR after 12 weeks. No bermekimab-related adverse events except injection site reactions |
| Bermekimab (MABp1, IL-1α inhibitor), SQ | Kanni et al. 2018 [47] | Phase 2 double-blind, randomized placebo-controlled |
Assess efficacy in patients with moderate-to-severe HS Endpoint: differences in achievement of HiSCR at week 12 between treatment and placebo group |
20 | February 2017 | 60% of patients in active arm achieved HiSCR compared with 10% in placebo arm |
| Bermekimab (MABp1, IL-1α inhibitor), SQ | NCT04988308 | Phase 2 randomized, placebo- and active comparator-controlled, double-blind |
Evaluate clinical efficacy in patients with moderate-to-severe HS Endpoint: percentage of patients achieving HiSCR |
151 | November 2022 | Terminated |
| Bermekimab (MABp1, IL-1α inhibitor), SQ | NCT04019041 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 12 |
144 | November 2020 | Completed |
| Lutikizumab/ABT-981 (ABT-981, IL-1α/β dual variable domain), SQ | NCT05139602 | Phase 2 multicenter, randomized, double-blind placebo-controlled |
Compare lutikizumab (ABT-981) versus placebo for the treatment of adults with moderate-to-severe HS who have failed anti-TNF therapy Endpoint: achievement of HiSCR at week 16 |
160 | December 2023 | Recruiting |
| PF 06650833 (IRAK4 inhibitor), oral | NCT04092452 | Phase 2 multicenter, randomized, double-blind placebo-controlled |
Compare three kinase inhibitors (PF 06650833, PF 06700841, and PF 06826647) with placebo in moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
194a | January 2022 | Completed, results submitted |
| KT-474 (heterobifunctional small-molecule IRAK4 degrader), oral | NCT04772885 | Phase 1 randomized, placebo-controlled |
Assess safety, tolerability, and pharmacokinetics/pharmacodynamics in healthy volunteers and in patients with atopic dermatitis and HS Endpoints: incidence and severity of emergent adverse events up to 28 days, incidence and frequency of concomitant medications up to 28 days |
154 | October 2022 | Completed |
| MAS-825 (IL-1β and IL-18 inhibitor), SQ | NCT03827798 | Phase 2 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
200b | May 2023 | Recruiting |
| Bimekizumab (IL-17A/F inhibitor), SQ | NCT04901195 | Phase 3 open-label, parallel group extension |
Assess safety of long-term treatment in patients with moderate-to-severe HS Endpoint: percentage of patients with treatment-emergent adverse events from baseline until week 120 |
830 | April 2025 | Active, not recruiting |
| Bimekizumab (IL-17A/F inhibitor), SQ | Kimball et al. 2023 (BE HEARD II) [61] | Phase 3 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
509 | September 2022 | 53.8% of patients receiving monthly dosing and 52% of patients receiving twice monthly dosing achieved HiSCR at week 16, compared with 32.2% of placebo |
| Bimekizumab (IL-17A/F inhibitor), SQ | Kimball et al. 2023 (BE HEARD I) [61] | Phase 3 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
505 | March 2023 | 45.3% of patients receiving monthly dosing and 47.8% of patients receiving twice monthly dosing achieved HiSCR at week 16, compared with 28.7% of placebo |
| Bimekizumab (IL-17A/F inhibitor), SQ | Glatt et al. 2021 [60] | Phase 2 multicenter, investigator-blind, subject-blind, placebo-controlled |
Assess efficacy, safety, and pharmacokinetics in patients with moderate-to-severe HS compared with adalimumab and placebo Endpoint: achievement of HiSCR at week 12 |
90 | February 2019 | Efficacious compared with placebo. 57.3% of 44 patients receiving bimekizumab achieved HiSCR at week 12 compared with 26.1% receiving placebo |
| Brodalumab (IL-17 inhibitor), SQ | Frew et al. 2020 [62] | Early phase 1 |
Identify biomarkers of disease activity and clinical response in patients with moderate-to-severe HS Endpoints: biomarkers at weeks 12/24 and TEAEs until week 24 |
10 | June 2020 | 100% achieved HiSCR at weeks 4 and 24. No serious adverse events were reported |
| Brodalumab (IL-17 inhibitor), SQ | Frew et al. 2021 [63] | Early phase 1 |
Identify biomarkers of disease activity and clinical response in patients with moderate-to-severe HS Endpoints: biomarkers at weeks 12/24 and TEAEs from week 0 to week 24 |
10 | September 2020 |
100% achieved HiSCR at weeks 4 and 24 No serious adverse events or thoughts of self-harm were reported during the study |
| Brodalumab (IL-17 inhibitor), SQ | NCT04979520 | Early phase 1 open-label |
Characterize molecular response to this treatment, identify blood and tissue markers reflecting disease severity, and better understand disease mechanisms Endpoint: IL-17A receptor saturation during brodalumab administration at week 12 versus baseline |
4 | July 2022 | Completed, results not available |
| CJM112 (IL-17A inhibitor), SQ | Kimball et al. 2022 [68] | Phase 2 randomized, double-blind, placebo-controlled |
To determine efficacy and safety of multiple doses in comparison to placebo Endpoint: Decrease in HS-PGA score by at least 2 points after 16 weeks |
66 | November 2016 | Endpoint achieved in 32.3% (10/31) after 16 weeks compared with 12.5% (4/32) with placebo |
| Izokibep (IL-17A inhibitor), SQ | Acelyrin Inc. 2023 | Phase 2b randomized, double-blind |
Evaluate efficacy, safety, and immunogenicity in adults with moderate-to-severe HS Endpoint: Achievement of HiSCR after 16 weeks |
180 | February 2024 | Part A data: 71% achieved HiSCR and 33% achieved HiSCR100 at week 12 |
| Secukinumab (IL-17A inhibitor), SQ | Kimball et al. 2023 (SUNRISE) [78] | Phase 3 randomized, double-blind |
Assess efficacy, safety, and tolerability of secukinumab at week 52 in subjects with moderate-to-severe HS Endpoint: Achievement of HiSCR after 16 weeks |
544 | July 2022 | Significant HiSCR rates of 42% (every 2 weeks) and 46% (every 4 weeks) dosing compared with placebo at week 16 |
| Secukinumab (IL-17A inhibitor), SQ |
Kimball et al. 2023 (SUNSHINE) [78] |
Phase 3 randomized, double-blind |
Assess efficacy, safety, and tolerability of secukinumab at week 52 in subjects with moderate-to-severe HS Endpoint: achievement of HiSCR after 16 weeks |
545 | July 2022 | Significant HiSCR rate of 45% (every-2-week dosing) compared with placebo at week 16 |
| Secukinumab (IL-17A inhibitor), SQ | NCT04179175 | Phase 3 randomized, triple-blind | Evaluate maintenance of HiSCR response at week 104 in either continuous or interrupted therapy, comparing every-2-week dosing to every-4-week dosing in HiSCR responders after 52 weeks, or switched to placebo. Endpoint: time to loss of response during 52 week treatment duration up to week 104 | 856 | July 2026 | Recruiting |
| Sonelokimab (IL-17A/F inhibitor), SQ | NCT05322473 | Phase 2 randomized, parallel-group, double-blind, placebo-controlled |
Demonstrate clinical efficacy and safety sonelokimab compared with placebo and adalimumab in the treatment of adult participants with moderate-to-severe HS Endpoint: percentage of participants achieving HiSCR75 after 12 weeks |
210 | November 2023 | Active, not recruiting |
|
Guselkumab (IL-23 inhibitor), SQ |
NCT03628924 | Phase 2 randomized, placebo-controlled, double-blind |
Assess efficacy, safety, and tolerability of 2 doses of guselkumab compared with placebo in adults with moderate-to-severe HS Endpoint: achievement of HiSCR after 16 weeks |
184 | May 2020 | HiSCR at week 16 (not significant): 50.8% of those on 200 mg SQ every 4 weeks, 45% of those on 1200 mg IV at weeks 0, 4, and 8 followed by 200 mg SQ at week 12 and thereafter, and 38.7% in placebo group |
|
Guselkumab (IL-23 inhibitor), SQ |
NCT04061395 | Phase 2, open label |
Investigate changes in inflammatory pathways induced by IL-23p19 blockade with guselkumab, in HS lesional skin Endpoint: changes in inflammatory pathways induced by IL-23p19 blockade with guselkumab |
20 | December 2020 | Unknown |
| Risankizumab (IL-23 inhibitor), SQ | Kimball et al. 2023 [111] | Phase 2 randomized, placebo-controlled, double-blind |
Assess safety and efficacy of risankizumab 180 mg and 360 mg versus placebo for moderate-to-severe HS in adults Endpoint: achievement of HiSCR after 16 weeks |
243 | August 2022 | No significant difference in HiSCR achievement between treatment groups. Primary endpoint was not achieved |
| Spesolimab (IL-36 inhibitor), IV and SQ | Alavi et al. 2023 [122] | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy in patients with moderate-to-severe HS Endpoint: change from baseline in AN count at week 12 |
52 | April 2022 | 38.8% decrease in AN count in treatment group compared with 34.7% decrease in placebo group |
| Spesolimab (IL-36 inhibitor), IV and SQ | NCT04876391 | Phase 2 open-label, long-term extension trial |
Evaluate long-term safety of spesolimab Endpoint: occurrence of TEAEs up to week 120 |
45 | April 2024 | Active, not recruiting |
| Imsidolimab/ANB019 (IL-36 inhibitor), IV and SQ | NCT04856930 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy in adults with HS and compare results with placebo Endpoint: change from baseline in AN count at week 16 |
149 | December 2022 | Completed |
| Avacopan/CCX168 (C5a receptor inhibitor), oral | ChemoCentryx 2020 [127] | Phase 2 randomized, double-blind, placebo-controlled, parallel group |
Evaluate efficacy and safety in subjects with moderate-to-severe HS Endpoint: achievement of HiSCR after 12 weeks |
435 | March 2021 | Primary endpoint not met. Subgroup analysis: 42.6% of Hurley stage III patients achieved HiSCR at higher dose compared with 22.2% of placebo (significant) |
| Vilobelimab/IFX-1 (anti-C5a antibody), IV | Giamarellos-Bourboulis et al. 2020 [128] | Phase 2 open-label trial |
Evaluate safety and tolerability in patients with moderate-to-severe HS Endpoint: number of patients with TEAEs and anti-drug antibodies up to day 134 |
12 | July 2017 | 75% achievement of HiSCR at day 50 |
| Vilobelimab/IFX-1 (anti-C5a antibody), IV | Giamarellos-Bourboulis et al. 2020 [124] | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate the safety and tolerability of vilobelimab compared with placebo in patients with moderate-to-severe HS Endpoint: achievement of HiSCR after 16 weeks |
179 | January 2020 | HiSCR achievement was not superior in treatment groups compared with placebo. IHS4 scores and draining fistulae count decreased with every other week dosing |
| BDB-001 (C5a inhibitor), IV | NCT05093855 | Phase 2 open-label |
Evaluate efficacy and safety in patients with moderate-to-severe HS Endpoint: change in IHS4 score from day 0 until week 8 |
49 | December 2023 | Recruiting |
| BDB-001 (C5a inhibitor), IV | NCT05103423 | Phase 2 randomized, double-blind placebo-controlled |
Evaluate efficacy and safety in adults with moderate-to-severe HS Endpoints: TEAEs, anti-BDB-001 antibody development, PK parameters |
49 | June 2023 | Recruiting |
| Iscalimab/CFZ533 (CD40 inhibitor), SQ | NCT03827798 | Phase 2 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
200b | May 2023 | Recruiting |
| LYS006 (leukotriene A4 hydrolase inhibitor), oral | NCT03827798 | Phase 2 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
200b | May 2023 | Recruiting |
| Povorcitinib/INCB054707 (JAK-1 inhibitor), oral | NCT04476043 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy and safety of INCB054707 in participants with moderate-to-severe HS over a 16-week placebo-controlled period, followed by a 36-week extension period Endpoint: mean change from baseline in AN count at week 16 |
209 | August 2023 | Statistically significant difference in AN count across 3 doses compared with placebo at week 16 |
| Povorcitinib/INCB054707 (JAK-1 inhibitor), oral | Alavi et al. 2022 [8] | Phase 2 placebo-controlled study |
Evaluate the safety of INCB054707 over an 8-week treatment period in patients with moderate-to-severe HS Endpoint: number of TEAEs at week 12 |
35 | August 2019 | 65% achieved HiSCR in treatment group vs. 57% in placebo after 8 weeks |
| Povorcitinib/INCB054707 (JAK-1 inhibitor), oral | Alavi et al. 2022 [8] | Phase 2 open-label, single-arm study |
Evaluate the safety of INCB054707 in patients with moderate-to-severe HS Endpoint: number of TEAEs at week 12 |
10 | April 2019 | 43% achieved HiSCR at week 8; 3 participants discontinued treatment |
| Povorcitinib/INCB054707 (JAK-1 inhibitor), oral | NCT05620823 (STOP-HS1) | Phase 3 randomized, double-blind, placebo-controlled |
Evaluate the efficacy and safety of INCB054707 in participants with moderate-to-severe HS over a 12-week placebo-controlled period, followed by a 42-week extension period Endpoint: proportion of patients who achieve HiSCR at week 12 |
600 | January 2026 | Recruiting |
| Povorcitinib/INCB054707 (JAK-1 inhibitor), oral | NCT05620836 (STOP-HS2) | Phase 3 randomized, double-blind, placebo-controlled |
Evaluate efficacy and safety of INCB054707 in participants with moderate-to-severe HS over a 12-week placebo-controlled period, followed by a 42-week extension period Endpoint: proportion of patients who achieve HiSCR at week 12 |
600 | January 2026 | Recruiting |
| Upadacitinib (JAK-1 inhibitor), oral | NCT04430855 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy and safety in participants with moderate-to-severe HS Endpoint: proportion of patients who achieve HiSCR at week 12 |
68 | January 2022 | 38.3% achieved HiSCR in treatment group and 23.8% in placebo group |
| Brepocitinib/PF06700841 (TYK2/JAK1 inhibitor), oral | NCT04092452 | Phase 2 randomized, double-blind, placebo-controlled |
Compare 3 kinase inhibitors (PF 06650833, PF 06700841, and PF 06826647) with placebo in moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
194a | January 2022 | Completed, results submitted |
| Ropsacitinib/PF06826647 (tyrosine kinase 2 inhibitor), oral | NCT04092452 | Phase 2 randomized, multicenter, double-blind, placebo-controlled |
Compare efficacy of 3 kinase inhibitors (PF 06650833, PF 06700841, and PF 06826647) with placebo in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
194a | January 2022 | Results submitted |
| Tofacitinib (JAK inhibitor), oral | NCT04246372 | Phase 2 open-label |
Evaluate efficacy and safety of 5 mg twice daily in the treatment of multiple inflammatory conditions, including HS, in participants with Down syndrome Endpoint: number of TEAEs up to week 18 and change in interferon scores in the transcriptome of white blood cells |
47 | December 2024 | Recruiting |
| Remibrutinib/LOU064 (BTK inhibitor), oral | NCT03827798 | Phase 2 randomized, double-blind, placebo-controlled |
Assess safety and efficacy in patients with moderate-to-severe HS Endpoint: achievement of HiSCR at week 16 |
200b | May 2023 | Recruiting |
| Fostamatinib (spleen tyrosine kinase inhibitor), oral | NCT05040698 | Phase 2 exploratory, proof-of-concept |
A proof-of-concept study to evaluate efficacy Endpoint: Alterations in gene expression profiling, cell counts (CD3+, CD11c+, Neutrophil Elastase+, CD20+, CD138+) at weeks 4 and 12 compared with baseline |
20 | January 2023 | Completed |
| Apremilast (PDE-4 inhibitor), oral | Kerdel et al. 2019 [142] | Phase 2 open-label |
Evaluate efficacy and safety in patients with moderate HS Endpoint: proportion of patients who achieve HiSCR at week 16 |
20 | August 2017 | 55% HiSCR rate at week 16 |
| Apremilast (PDE-4 inhibitor), oral | Vossen et al. 2019 [143] | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy and short-term safety in patients with moderate HS Endpoint: proportion of patients who achieve HiSCR at week 16 |
20 | June 2018 | 53.3% in treatment group met HiSCR and 0% in placebo met HiSCR |
| Orismilast (PDE-4 inhibitor), oral | NCT04982432 | Phase 2 open-label |
Evaluate efficacy and safety for the treatment of mild, moderate, or severe HS in adults Endpoint: change from baseline in AN count at week 16 |
24 | December 2022 | Not yet recruiting |
| PTM-001 (glycan-targeting antibody), oral | NCT05020730 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate immunomodulatory activity of PTM-001 in participants with HS Endpoint: effect of PTM-001 on IL-1β protein levels in lesional skin biopsies at week 12 |
50 | June 2024 | Recruiting |
| RIST 4721 (CXCR2 antagonist), oral | NCT05348681 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy and safety in patients with HS Endpoint: incidence of TEAEs and SAEs until week 12 |
25 | February 2023 | Terminated |
| Eltrekibart/LY3041658 (ELR and CXC chemokine neutralizer), IV | NCT04493502 | Phase 2 randomized, double-blind, placebo-controlled |
Evaluate efficacy in patients with moderate-to-severe HS Endpoint: percentage of patients who achieve HiSCR at week 16 |
67 | October 2022 | 65.6% in treatment group met HiSCR compared with 41.4% in placebo group |
| Zunsemetinib/ATI-450 (small-molecule MK2 inhibitor), oral | Aclaris Therapeutics 2023 [157] | Phase 2 randomized, double-blind placebo-controlled |
Evaluate efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of ATI-450 versus placebo in patients with moderate-to-severe HS Endpoint: change in AN count at week 12 |
95 | January 2023 | Did not meet primary or secondary endpoints |
| CSL324 (anti-GCSF receptor), IV | NCT03972280 | Phase 1 open-label |
Evaluate safety and PK of repeat doses in subjects with HS or palmoplantar pustulosis Endpoints: incidence of TEAEs and AESIs up to 24 weeks |
39 | October 2022 | Completed |
| RGRN-305 (HSP90 inhibitor), oral | NCT05286567 | Phase 1 randomized, double-blind, placebo-controlled |
Evaluate efficacy in patients with moderate-to-severe HS Endpoint: percentage of patients who achieve HiSCR at week 16 |
15 | August 2022 | Completed |
AI autoinjector, AN abscess and inflammatory nodule, AUC0–∞ area under the concentration–time curve from time 0 extrapolated to infinity, AUC0–t area under the concentration–time curve from time 0 to the last quantifiable concentration, BTK bruton tyrosine kinase, C5a complement component 5a, Cmax maximum observed concentration, CXCR c-x-c chemokine receptor, DLQI Dermatology Life Quality Index, GCSF granulocyte colony-stimulating factor, HiSCR hidradenitis suppurativa clinical response, HS hidradenitis suppurativa, IHS4 International Hidradenitis Suppurativa Severity Score, IL interleukin, IRAK4 IL-1 receptor associated kinase 4, IV intravenous, JAK Janus kinase, MK2 mitogen-activated protein kinase (MAPK)-activated protein kinase-2, MOA mechanism of action, PDE phosphodiesterase, PFS pre-filled syringe, PGA Physician Global Assessment, PK pharmacokinetics, SQ subcutaneous, TEAEs treatment emergent adverse events, TNF tumor necrosis factor, TYK tyrosine kinase
aIncluding patients on PF 06650833, PF 06700841, and PF 06826647
bIncluding patients on MAS825, CFZ533, LYS006, and LOU064