Table 2.
Targeted therapies currently in clinical development in BP, CSU, PN, and CPUO
| Targeted molecule/pathway | Therapeutic product | Randomized placebo-controlled clinical trial | Current stage | Key efficacy outcomes | |
|---|---|---|---|---|---|
| BP | IL-4Rα (IL-4 and IL-13) | Dupilumab | BP ADEPT, phase II/III (NCT04206553) | Approved [25] (adult patients with BP) |
The proportion of patients achieving sustained remissiona at week 36 was 18.3% with dupilumab and 6.1% with placebo The proportion of patients achieving a ≥4-point improvement from baseline in PP-NRS at week 36 was 38.3% with dupilumab and 10.5% with placebo [25] |
| CSU | Free IgE | Omalizumab | NCT01287117 and NCT01292473 | Approved [97] (patients ≥12 years of age with CSU who remain symptomatic despite H1-antihistamine treatment) |
Mean change from baseline in ISS7 (SD) at week 12 was -6.66 (6.28) with omalizumab 150 mg, -9.40 (5.73) with omalizumab 300 mg, and -3.63 (5.22) with placebo Mean change from baseline in HSS7 (SD) at week 12 was -7.78 (7.08) with omalizumab 150 mg, -11.35 (7.25) with omalizumab 300 mg, and -4.37 (6.60) with placebo [97] |
| IL-4Rα (IL-4 and IL-13) | Dupilumab |
CUPID Study A and Study C (NCT04180488) |
Approved [25] (patients ≥12 years of age with CSU who remain symptomatic despite H1-antihistamine treatment) |
Study A/C mean change (SE) from baseline in ISS7 at week 24 was -10.44 (0.92)/-8.50(1.39) with dupilumab and -6.02(0.94)/-6.13(1.38) with placebo Study A/C mean change (SE) from baseline in UAS7 at week 24 was -20.99 (1.77)/-15.61(2.62) with dupilumab and -11.95(1.81)/-11.27(2.61) with placebo [25] |
|
| BTK | Remibrutinib | REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) | Approved [101] (adult patients with CSU who remain symptomatic despite H1-antihistamine treatment) |
REMIX-1/REMIX-2 mean change (SE) from baseline in ISS7 at week 12 was -9.52 (0.34)/-8.95 (0.34) with dupilumab and -6.89 (0.47)/-5.72 (0.45) with placebo REMIX-1/REMIX-2 mean change (SE) from baseline in HSS7 at week 12 was -10.47 (0.40)/-10.47 (0.39) with dupilumab and -6.86 (0.55)/-6.00 (0.53) with placebo REMIX-1/REMIX-2 mean change (SE) from baseline in UAS7 at week 12 was -20.02 (0.72)/-19.41 (0.70) with dupilumab and -13.79 (0.98)/-11.73 (0.95) with placebo [101] |
|
| KIT | Barzolvolimab |
EMBARQ-CSU1 (NCT06445023) [107] and EMBARQ-CSU2 (NCT06455202) [108] |
Phase III |
Results from the phase III studies not yet available In the phase II study NCT05368285, mean change (SE) from baseline in UAS7 at week 12 with barzolvolimab 75 mg q4w/150 mg q4w/300 mg q8w was -17.06 (1.493)/-23.02 (1.416)/-23.87 (1.479) and with placebo was -10.47 (1.462) [106] |
|
| PN | IL-4Rα (IL-4 and IL-13) | Dupilumab | PN PRIME (NCT04183335) and PN PRIME2 (NCT04202679) | Approved [25] (adults with PN) |
PRIME/PRIME2 proportion of patients with a ≥4-point reduction from baseline in WI-NRS at week 24 was 60.0%/57.7% with dupilumab and 18.4%/19.5% with placebo PRIME/PRIME2 proportion of patients with an IGA PN-S score 0 or 1 at week 24 was 48.0%/44.9% with dupilumab and 18.4%/15.9% with placebo [25] |
| IL-31RA | Nemolizumab | OLYMPIA 1 (NCT04501666) and OLYMPIA 2 (NCT04501679) | Approved [130] (adults with PN) |
OLYMPIA 1/OLYMPIA 2 proportion of patients with a ≥4-point reduction from baseline in PP-NRS at week 16 was 56.0%/49.0% with nemolizumab and 16.0%/16.0% with placebo OLYMPIA 1/OLYMPIA 2 proportion of patients with IGA 0 or 1 at week 16 was 26.0%/38.0% with nemolizumab and 7.0%/11.0% with placebo [130] |
|
| Oncostatin M receptor (IL-31 and oncostatin M) | Vixarelimab | NCT03816891 | Phase IIb randomized clinical trial |
The proportion of patients achieving a ≥4-point reduction from baseline in WI-NRS at week 16 with vixarelimab high-dose/mid-dose/low-dose was 66.0%/61.7%/29.8% and 16.7% with placebo The proportion of patients achieving an IGA-PN score 0 or 1 at week 16 with vixarelimab high/mid/low-dose was 38.3%/29.8%/14.9% and 10.4% with placebo [132] |
|
| JAK1 | Povorcitinib | STOP-PN1 (NCT06516952) [134] and STOP-PN2 (NCT06516965) [135] | Phase III randomized, double-blind, placebo-controlled clinical trial (recruiting) | Not yet available | |
| CPUO | IL-4Rα (IL-4 and IL-13) | Dupilumab | LIBERTY-CPUO-CHIC (NCT05263206) [147] | Phase III randomized, double-blind, placebo-controlled clinical trial (recruiting) | Not yet available |
| IL-31 | Nemolizumab | NCT07074977 [148] | Phase II (recruiting) | Not yet available | |
| JAK1 | Abrocitinib | NCT05038982 | Phase II open-label, non-randomized | Proportion of patients with a ≥4-point reduction from baseline in PP-NRS at week 12 was 60.0% [149] |
BP bullous pemphigoid, BTK Bruton tyrosine kinase, CPUO chronic prurigo of unknown origin, CSU chronic spontaneous urticaria, HSS7 Hive Severity Score over 7 days [0–21], IGA PN-S Investigator’s Global Assessment for Prurigo Nodularis-Stage [0–4], IgE immunoglobin E, IL interleukin, IL-31RA interleukin 31 receptor alpha, IL-4Rα interleukin 4 receptor alpha, ISS7 Itch Severity Score over 7 days [0–21], JAK1 Janus kinase 1, KIT tyrosine-protein kinase KIT, OCS oral corticosteroids, PP-NRS Peak Pruritus-Numerical Rating Scale [0–10], PN prurigo nodularis, q4w every 4 weeks, q8w every 8 weeks, SD standard deviation, SE standard error, UAS7 Urticaria Activity Score over 7 days [0–42], WI-NRS Worst Itch-Numerical Rating Scale [0–10]
aComplete remission defined as the achievement of complete remission and off OCS no later than week 16, absence of disease relapse from the completion of the corticosteroid taper to week 36, and absence of rescue therapy during the 36-week double-blind treatment period