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Pipeline Drugs for Vasculitis
Hibah Khaja, PharmD | Publish Date: May 9, 2025
https://www.rheumatologyadvisor.com/features/pipeline-drugs-for-vasculitis/
Small Vessel Vasculitis
Small vessel vasculitides, including GPA, EGPA, and MPA, are frequently linked to AAV. Emerging therapies for these conditions focus on enhancing remission rates while minimizing the adverse effects associated with traditional immunosuppressive treatments.
GPA, EGPA and MPA
Avacopan (CCX168): The C5a receptor inhibitor avacopan demonstrated significant efficacy for reducing glucocorticoid use while maintaining remission among patients with AAV, including GPA and MPA. In the phase 3 ADVOCATE trial (ClinicalTrials.gov Identifier: NCT02994927), patients who received avacopan achieved sustained remission at 52 weeks (65.7% vs 54.9% with standard therapy).4
Benralizumab: The anti-interleukin [IL]-5 receptor monoclonal antibody benralizumab demonstrated noninferiority to mepolizumab in the phase 3 MANDARA trial (ClinicalTrials.gov Identifier: NCT04157348), achieving remission at week 36 among 58% of patients with EGPA and enabling corticosteroid tapering to 4 mg/day or less in a greater percentage of patients.5
Iptacopan (LNP023): The oral complement factor B inhibitor iptacopan is being investigated in a phase 2 trial (ClinicalTrials.gov Identifier: NCT06388941) for its potential to reduce inflammation among patients with AAV. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The opioid receptor antagonist naltrexone is being investigated in the phase 2 LoDoNaVasc study (ClinicalTrials.gov Identifier: NCT03482479) for its potential to improve health-related quality of life (HRQOL) among patients with various vasculitides, including but not limited to GPA, MPA, and EGPA. The trial is ongoing, with no published outcomes to date.
Henoch-Schönlein Purpura
Rituximab, infliximab, tocilizumab: These biologics are being studied in the phase 3, multicenter, randomized, double-blind, placebo-controlled, modified-crossover BIOVAS trial (ClinicalTrials.gov Identifier: NCT05168475) evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including Henoch-Schönlein purpura) among both adults and children. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with Henoch-Schönlein purpura. The trial is ongoing, with no published outcomes to date.
Medium-Vessel Vasculitis
Advancements in targeted therapies for medium vessel vasculitides, such as PAN and KD, have been limited. However, emerging research offers potential for progress in this area.
KD:
Defibrotide: The endothelial stabilizing agent defibrotide is being investigated in a phase 2 pilot study (ClinicalTrials.gov Identifier: NCT04777422) to evaluate its safety in combination with intravenous immunoglobulins (IVIG) among children with high-risk KD. The trial is ongoing, with no published outcomes to date.
Anakinra: The IL-1 receptor antagonist anakinra is being evaluated in the phase 3, multicenter, randomized, open-label ANACOMP trial (ClinicalTrials.gov Identifier: NCT04656184) to compare its efficacy and safety against a second IVIG infusion among patients with KD who failed to respond to initial standard IVIG treatment. Researchers aim to determine whether anakinra is superior in resolving fever, with the achievement of a body temperature below 38°C within 2 days of treatment initiation as the primary endpoint. The trial is ongoing, with no published outcomes to date.
PAN: Emerging therapies aim to enhance existing treatment approaches, particularly through biologics that target the tumor necrosis factor-alpha and IL-6 pathways. However, the absence of large-scale trials remains a significant limitation due to the rarity of the condition.
Rituximab, infliximab, tocilizumab: These biologics are being studied in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including PAN) among both adults and children. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with PAN. The trial is ongoing, with no published outcomes to date.
Large-Vessel Vasculitis
Large vessel vasculitides, such as GCA and TAK, often require long-term treatment to prevent vascular complications.
GCA:
Abatacaept: The cytotoxic T-lymphocyte antigen 4 immunomodulator abatacept is being studied for GCA, showing potential for achieving remission and preventing relapses by modulating T-cell activation. In a phase 3, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04474847), researchers are evaluating the efficacy of subcutaneous abatacept 125 mg per week among patients with newly diagnosed or relapsing GCA. The trial includes 62 patients randomly assigned in a 1:1 ratio to receive either abatacept or placebo. Patients achieving remission will remain on their assigned treatment for 12 months, after which treatment will be stopped. Those not in remission by month 3 or who relapse within the first 12 months will have the option to receive open-label abatacept for up to 12 months. This study is currently recruiting participants and the outcomes are yet to be determined.
Rituximab, infliximab, tocilizumab: Tocilizumab, already US Food and Drug Administration-approved for the treatment of GCA, is now the focus of new studies exploring its long-term outcomes and potential combination therapies. These biologics are being further investigated in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for managing refractory non-ANCA-associated vasculitis (including GCA) among both adults and children. The trial is ongoing, and outcomes have yet to be published.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with GCA. The trial is currently ongoing, with no published outcomes to date.
TAK:
Upadacitinib: The JAK inhibitor upadacitinib is being investigated in the phase 3, multicenter, randomized, double-blind, placebo-controlled SELECT-TAK study (ClinicalTrials.gov Identifier: NCT04161898) for its potential to improve outcomes among patients with TAK. Researchers are evaluating the efficacy and safety of upadacitinib in combination with a corticosteroid taper regimen compared with placebo. The study is ongoing, with no published outcomes to date.
Tofacitinib: The JAK inhibitor tofacitinib is currently being evaluated in a phase 3, prospective, randomized, double-blind, single-center trial (ClinicalTrials.gov Identifier: NCT05749666) comparing its efficacy and safety with prednisolone for the treatment of active TAK. The primary endpoint is the percentage of patients achieving complete response at week 24. Efficacy will be evaluated at weeks 4, 12, and 24, while safety is also monitored throughout the trial. The study is ongoing, with no published outcomes to date.
Rituximab, infliximab, tocilizumab: These biologics are being studied in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including TAK) among both adults and children. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with TAK. The trial is currently ongoing, with no published outcomes to date.