What is the mechanism of action of this treatment?

Common treatments for Systemic Lupus Erythematosus (SLE) often involve monoclonal antibodies that target specific components of the immune system. For example, BIIB059 (litifilimab) targets blood dendritic cell antigen 2 (BDCA2), which regulates type I interferon production, a crucial pathway in SLE pathogenesis. By inhibiting this pathway, BIIB059 aims to reduce disease activity. Other treatments, such as rituximab, target CD20-positive B cells to deplete B cells and reduce autoantibody production. These mechanisms are vital for SLE patients as they help modulate the overactive immune response, reduce inflammation, and prevent organ damage.

What side effects are associated with this type of intervention?

Common treatments for Systemic Lupus Erythematosus (SLE) that are similar to BIIB059 (litifilimab) include monoclonal antibodies like rituximab and belimumab. Rituximab, which targets CD20 on B lymphocytes, can cause side effects such as life-threatening infections, pancytopenia, severe mucocutaneous reactions, and bowel obstruction. Belimumab, which inhibits B-lymphocyte stimulator (BLyS), may lead to nausea, diarrhea, fever, and increased risk of infections. General side effects of immunosuppressive therapies used in SLE include increased susceptibility to infections, liver toxicity, and gastrointestinal disturbances.

What prior FDA approvals exist?

The FDA has approved several treatments for Systemic Lupus Erythematosus (SLE), including biologics that target specific pathways involved in the disease. Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), was the first biologic approved for SLE. Anifrolumab, another monoclonal antibody, targets the type I interferon receptor and was approved for SLE due to its role in reducing type I interferon activity, similar to the mechanism of BIIB059 (litifilimab). These treatments aim to modulate the immune system and reduce disease activity in SLE patients.

What other types of research exist?

<ol> <li>Belimumab (Benlysta®): Approved for the treatment of active lupus nephritis, belimumab is a monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), reducing the survival of B cells and thereby decreasing the autoimmune response in SLE patients. It is available in both intravenous and subcutaneous forms.</li> <li>Obinutuzumab: A next-generation humanized type-2 anti-CD20 antibody, obinutuzumab has shown efficacy in SLE patients with secondary non-response to rituximab.</li> </ol> It targets CD20 on B cells, leading to their depletion. 3. Tofacitinib: A Janus kinase (JAK) inhibitor, tofacitinib has been used successfully in refractory cutaneous dermatomyositis, which shares some pathophysiological features with SLE. It inhibits the JAK-STAT pathway, which is involved in the immune response. 4. Ibrutinib: A Bruton tyrosine kinase (BTK) inhibitor, ibrutinib has shown durable single-agent activity in B cell malignancies and may offer potential benefits in SLE by inhibiting B cell receptor signaling pathways. 5. Checkpoint Inhibitors (e.g., Nivolumab, Pembrolizumab): These agents target PD-1/PD-L1 pathways and have shown promise in various malignancies. Their role in autoimmune conditions like SLE is being explored, although they come with a risk of autoimmune toxicities.

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Monoclonal Antibodies

Litifilimab for Systemic Lupus Erythematosus (TOPAZ-2 Trial)

Phase 3

Waitlist Available

Research Sponsored by Biogen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Are your SLE symptoms active now? Common symptoms include: ongoing fever, painful, swollen joints, increased fatigue, rash, or general swilling in the legs.

Have you been diagnosed by a doctor with Systemic Lupus Erythematosus (SLE)?

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 40 up to week 52

Awards & highlights

Pivotal Trial

Summary

A clinical study is now available in your area for rhinosinusitis with nasal polyps. Treatment may offer you symptom relief and eliminate the need for surgery. Answer a few short questions below to see if you may qualify.

Who is the study for?

Adults with active Systemic Lupus Erythematosus (SLE) who are on standard nonbiologic lupus treatments can join. They must have been diagnosed at least 24 weeks ago, meet specific SLE criteria, and not be taking high doses of corticosteroids or certain other medications. People with severe kidney issues, serious infections like herpes or hepatitis, HIV, heart failure, or skin conditions other than CLE cannot participate.

What is being tested?

The trial is testing the effectiveness and safety of a drug called BIIB059 (litifilimab) versus a placebo in reducing SLE activity while participants continue their usual lupus treatments. It also looks at how quickly it works for joint and skin symptoms, its impact on steroid use and quality of life up to Week 52.

What are the potential side effects?

Possible side effects include reactions related to the immune system since litifilimab targets inflammation pathways involved in lupus. Specific side effects aren't listed but may resemble those seen with similar drugs such as infusion reactions, infections due to lowered immunity, or allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My SLE symptoms are currently active, including fever, joint pain, fatigue, rash, or leg swelling.

Select...

I have been diagnosed with Systemic Lupus Erythematosus (SLE).

Select...

I am currently on medication for SLE.

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I am not taking steroids, or my dose is under 20 mg daily.

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I am taking antimalarial medication for my lupus.

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I am not currently taking and have not taken Saphnelo.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 40 up to week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 40 up to week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 40 up to week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index of 4 (SRI-4) Response at Week 52

Secondary study objectives

Annualized Flare Rate Through Week 52

Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score

Change from Baseline in Lupus-Specific Health-Related Quality-of-Life Questionnaire (LupusQoL) Score

+22 more

Side effects data

From 2019 Phase 2 trial • 264 Patients • NCT02847598

17%

Neutrophil count increased

17%

Diarrhoea

17%

Nausea

17%

Neutrophilia

17%

Cystitis

17%

Urticaria

17%

Pruritus

17%

Rhinitis

17%

Nasopharyngitis

17%

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Part A: Placebo

Part A: BIIB059 50 mg

Part A: BIIB059 150 mg

Part A: BIIB059 450 mg

Part B: Placebo

Part B: BIIB059 50 mg

Part B: BIIB059 150 mg

Part B: BIIB059 450 mg

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: BIIB059 Low DoseExperimental Treatment1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive low dose of BIIB059, SC Q4W, up to Week 48 with an additional dose at Week 2.

Group II: BIIB059 High DoseExperimental Treatment1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive high dose of BIIB059, subcutaneously (SC), every 4 weeks (Q4W), up to Week 48 with an additional dose at Week 2.

Group III: PlaceboPlacebo Group1 Intervention

Participants who are receiving background nonbiologic lupus SOC therapy will receive BIIB059 matching placebo, SC Q4W, up to Week 48 with an additional dose at Week 2.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

BIIB059 (litifilimab)

2016

Completed Phase 2

~380

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Systemic Lupus Erythematosus (SLE) often involve monoclonal antibodies that target specific components of the immune system. For example, BIIB059 (litifilimab) targets blood dendritic cell antigen 2 (BDCA2), which regulates type I interferon production, a crucial pathway in SLE pathogenesis. By inhibiting this pathway, BIIB059 aims to reduce disease activity. Other treatments, such as rituximab, target CD20-positive B cells to deplete B cells and reduce autoantibody production. These mechanisms are vital for SLE patients as they help modulate the overactive immune response, reduce inflammation, and prevent organ damage.

Upcoming therapeutic targets in cutaneous lupus erythematous.Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus.