Lancovutide

Summary

Lancovutide (also known as duramycin, Moli1901) is an investigational peptide being studied for cystic fibrosis. Delivered by inhalation, it is intended to increase airway surface liquid by activating a calcium‑dependent chloride channel, thereby promoting mucus hydration and clearance.

Mechanism of Action

Pre‑clinical work shows lancovutide stimulates chloride efflux through the calcium‑activated chloride channel TMEM‑16A (a CaCC) in cystic fibrosis bronchial epithelial cells. The effect appears concentration‑dependent, with maximal activity near 1 µM and inhibition at higher levels. Inhibition of CFTR or blockade of capacitative calcium entry reduces the response, suggesting the peptide’s action involves membrane perturbation that raises intracellular calcium and opens TMEM‑16A, bypassing the defective CFTR channel.

What the Research Shows

Early in‑vitro studies reported that lancovutide increased chloride secretion in CF bronchial cells at low micromolar concentrations, an effect blocked by CFTR inhibitors and calcium‑entry blockers, implying a non‑specific membrane effect rather than direct CaCC activation. Review articles (2011, 2009, 2015) classified the peptide as an early‑phase, airway‑re‑hydrating agent that activates an alternate chloride pathway. A 2021 randomized, double‑blind, placebo‑controlled trial in 161 patients aged 12 years and older administered inhaled lancovutide (2.5 mg) on three dosing schedules for eight weeks. The study found no significant improvement in FEV1 percent predicted or other lung‑function measures, although inhalation was generally safe. Thus, pre‑clinical promise has not yet translated into demonstrated clinical efficacy.

Reported Benefits

Laboratory data suggest lancovutide can raise chloride transport and potentially increase airway surface liquid, which could improve mucus clearance in cystic fibrosis. The peptide’s mechanism bypasses the defective CFTR protein, offering a theoretical advantage for patients with mutations unresponsive to existing CFTR modulators.

Limitations of the Evidence

Human data are limited to an early‑phase trial that showed no measurable lung‑function benefit, and the peptide exhibited a narrow effective concentration range in vitro, with higher doses inhibiting chloride efflux. Evidence of clinical efficacy remains lacking, and the drug has not progressed beyond early investigational stages. Potential interactions with other airway‑re‑hydrating agents are unknown.

Safety Considerations

In the 2021 trial, lancovutide was generally well tolerated, but participants experienced a higher incidence of respiratory‑related adverse events (e.g., cough, bronchospasm) compared with placebo. No serious systemic toxicities were reported. Ongoing safety monitoring is required, especially regarding airway irritation with repeated inhalation.

How It Is Administered

Lancovutide is administered as an aerosolized inhalation solution. In the published trial, a 2.5 mg dose was given once daily, every other day, or twice weekly for eight weeks via nebulizer. Formulation details beyond the inhaled solution were not provided in the abstracts.

Routes of Administration

Goals & Uses

• Airway surface liquid hydrationRespiratory / PharmacodynamicModerate
• Mutation-agnostic CF therapyTherapeutic PositioningModerate
• Improvement of mucociliary clearance in cystic fibrosisRespiratory / Disease ManagementModerate

Contraindications

• Severe bronchospasm or reactive airway diseaseRespiratoryModerate
• Known hypersensitivity to lancovutide or duramycinAllergyHigh

Adverse Effects

• CoughRespiratoryCommonPersistent or episodic cough
• HemoptysisRespiratoryRare
• BronchospasmRespiratoryUncommon
• Dysgeusia (altered taste)SensoryUncommon
• Throat irritationLocal / RespiratoryCommon

Drug Interactions

• Bronchodilators (e.g., salbutamol)Low
• Inhaled tobramycinLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients under 6 yearsAgeRelative
• Renal or hepatic impairmentOrgan DysfunctionRelative

Regulatory Status

• European UnionInvestigationalOrphan medicinal product designation granted by EMA for cystic fibrosis. Not approved.
• United StatesInvestigationalOrphan Drug Designation granted by FDA for cystic fibrosis. Not approved for marketing.

Lancovutide has received Orphan Drug Designation in the US and EU for cystic fibrosis. It has not received full marketing approval in any jurisdiction as of the knowledge cutoff.

Evidence & Sources

• Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia
  Journal ArticleLowOliynyk I, et al.2010-01-01T00:00:00.000000Z
• Therapeutic options for hydrating airway mucus in cystic fibrosis
  Journal ArticleModerateTildy BE, Rogers DF2015-01-01T00:00:00.000000Z
• Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial
  Journal ArticleModerateEber E, et al.2021-01-01T00:00:00.000000Z
• Airway-rehydrating agents for the treatment of cystic fibrosis: past, present, and future
  Journal ArticleModeratePettit RS, Johnson CE2011-01-01T00:00:00.000000Z
• Emerging treatments in cystic fibrosis
  Journal ArticleLowJones AM, Helm JM2009-01-01T00:00:00.000000Z

Frequently Asked Questions