Dapirolizumab pegol

Summary

Dapirolizumab pegol (DZS-SLE) is an investigational PEGylated anti-CD40L Fab' fragment developed primarily for systemic lupus erythematosus (SLE). It lacks an Fc region to avoid platelet-mediated thromboembolic events seen with earlier anti-CD40L antibodies. Phase II and Phase III clinical trials in SLE have been conducted, showing signals of clinical benefit. It is not yet approved by any regulatory authority.

Mechanism of Action

Dapirolizumab pegol is a PEGylated anti-CD40L (CD154) Fab' fragment that blocks the CD40L–CD40 costimulatory pathway, thereby inhibiting T cell–dependent B cell activation, autoantibody production, and downstream inflammatory cytokine release.

Routes of Administration

Goals & Uses

• Reduction of lupus flaresAutoimmune/InflammatoryModerate
• Reduction of autoantibody titers (anti-dsDNA)Biomarker/SerologicalModerate
• Reduction of SLE disease activityAutoimmune/InflammatoryModerate
• Steroid-sparing effect in SLEAutoimmune/InflammatoryLow
• Treatment of lupus nephritisRenal/AutoimmuneLow

Contraindications

• Known hypersensitivity to dapirolizumab pegol or PEGImmunologicHigh
• Active serious infectionsInfectiousHigh
• Active tuberculosisInfectiousHigh

Adverse Effects

• NasopharyngitisInfectiousCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Thromboembolic eventsCardiovascularRare
• Infections (upper respiratory, urinary tract)InfectiousCommon
• Serious infectionsInfectiousUncommon
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• Live vaccinesHigh
• Other immunosuppressants (mycophenolate, azathioprine, cyclophosphamide)Moderate
• CorticosteroidsLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Patients with history of recurrent serious infectionsInfectiousRelative
• Pediatric patientsAgeRelative
• Renal impairment (severe)RenalRelative

Regulatory Status

• European UnionInvestigationalPhase III trials conducted in EU sites; no EMA approval as of early 2025.
• United StatesInvestigationalPhase III trials ongoing (PHOENYCS GO, PHOENYCS FLY) for SLE; no FDA approval as of early 2025.
• United KingdomInvestigationalParticipated in international trials; no MHRA approval as of early 2025.

No regulatory approvals granted as of early 2025. Phase III PHOENYCS GO and PHOENYCS FLY trials in SLE are ongoing/recently completed. Breakthrough Therapy designation not publicly confirmed; regulatory submissions pending trial outcomes.

Evidence & Sources

No sources recorded yet.