Alisporivir

Cyclic Peptide (cyclophilin Inhibitor, Cyclosporine Analogue)Rx: InvestigationalCompound: Investigational

Also known as: ALV, Cyclophilin inhibitor Debio 025, DEB025, Debio 025

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

Alisporivir (formerly Debio 025) is an oral, non-immunosuppressive cyclic peptide cyclophilin inhibitor developed primarily for chronic hepatitis C infection. It demonstrated pan-genotypic antiviral activity in clinical trials by targeting host cyclophilin A rather than viral proteins, reducing resistance risk. Development was paused in 2012 following cases of pancreatitis during Phase III trials but was later resumed. It has also been investigated for mitochondrial diseases due to its mPTP inhibition.

Mechanism of Action

Non-immunosuppressive cyclosporine A analogue that binds and inhibits cyclophilin A (CypA), thereby blocking the CypA–NS5B interaction required for hepatitis C virus (HCV) RNA replication. Also inhibits mitochondrial permeability transition pore (mPTP) opening, conferring cytoprotective effects.

Routes of Administration

Oral

Goals & Uses

  • Treatment of chronic hepatitis C infectionAntiviral / Infectious DiseaseModerate
  • Prevention of ischemia-reperfusion injuryCardioprotection / CytoprotectionLow
  • Combination antiviral therapy (with pegIFN/ribavirin or DAAs)Antiviral Combination RegimenModerate
  • Treatment of mitochondrial diseases (e.g., MELAS, Sengers syndrome)Rare / Orphan DiseaseLow

Contraindications

  • Hypersensitivity to cyclosporine analoguesAllergy / ImmunologyHigh
  • Severe hepatic impairmentOrganModerateLiver function concerns
  • History of pancreatitisGastrointestinalHigh

Adverse Effects

  • HeadacheNeurologicCommonPain in the head or upper neck
  • Elevated liver enzymes (ALT/AST)HepaticUncommon
  • NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
  • FatigueGeneralCommonLow energy or tiredness
  • Acute pancreatitisGastrointestinalUncommon
  • HyperbilirubinemiaHepaticCommon

Drug Interactions

  • Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)High
  • Cyclosporine AModerate
  • Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
  • P-glycoprotein substratesModerate

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Renal impairmentOrgan ImpairmentRelative
  • Pediatric patientsAgeRelative
  • Patients with prior pancreatitis or risk factors for pancreatitisGastrointestinalAbsolute

Regulatory Status

  • European UnionInvestigationalEMA has not approved alisporivir for any indication. Orphan designation sought for mitochondrial diseases.
  • United StatesInvestigationalFDA clinical hold placed in 2012 due to pancreatitis; subsequently lifted. No approved indication as of current knowledge cutoff.
  • United KingdomInvestigationalNot approved by MHRA. Status mirrors EMA investigational designation.

FDA placed a clinical hold on alisporivir trials in 2012 due to pancreatitis cases; the hold was subsequently lifted. The compound has not received FDA or EMA approval for any indication. Orphan Drug Designation has been pursued for certain rare mitochondrial disease indications.

Evidence & Sources

No sources recorded yet.

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