PRO-542

Summary

PRO-542 (CD4-IgG2) is a recombinant fusion protein combining four CD4 domains with human IgG2 heavy and light chains, giving it tetravalent binding to HIV-1 gp120. It was investigated as an HIV-1 entry inhibitor in both adults and pediatric patients with HIV-1 infection. Clinical trials demonstrated antiviral activity and good tolerability, but development was not advanced to regulatory approval, partly due to the emergence of small-molecule entry inhibitors.

Mechanism of Action

PRO-542 is a tetravalent CD4-IgG2 fusion protein that mimics the HIV-1 gp120 binding site on CD4. It competitively inhibits HIV-1 entry by binding with high affinity to gp120 on the viral surface, preventing virus attachment to host cell CD4 receptors and blocking subsequent coreceptor engagement and membrane fusion.

Routes of Administration

Goals & Uses

• Pediatric HIV-1 treatmentAntiviral TherapyLow
• Salvage therapy for treatment-experienced HIV patientsAntiviral TherapyLow
• HIV-1 entry inhibitionMechanism Based Viral SuppressionModerate
• HIV-1 viral load reductionAntiviral EfficacyModerate

Contraindications

• Hypersensitivity to CD4-IgG2 or IgG2-based biologicsImmunologicHigh

Adverse Effects

• Flu-like symptomsSystemic/ImmunologicalUncommon
• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• Immunogenicity / anti-drug antibodiesImmunologicUncommon

Drug Interactions

• Antiretroviral agents (combination ART)Low

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients < 2 yearsAgeRelative
• Renal or hepatic impairmentOrgan DysfunctionRelative

Regulatory Status

• European UnionInvestigationalNo marketing authorization granted by EMA
• United StatesInvestigationalStudied under IND; Phase I/II completed; never approved by FDA
• United KingdomInvestigationalNo regulatory approval in the UK

PRO-542 was studied in Phase I/II clinical trials. It was never submitted for or granted regulatory approval by FDA, EMA, or other agencies. It remains an investigational compound. Developed by Progenics Pharmaceuticals.

Evidence & Sources

No sources recorded yet.