Rezafungin

Rezafungin is anidulafungin with a choline sulfate group substituted at the hemiaminal position — the site responsible for the parent molecule's chemical instability and degradation. The result is a molecule with the same target (the FKS-encoded 1,3-beta-D-glucan synthase complex) and the same spectrum, but front-loaded pharmacokinetics: high peak concentrations, minimal metabolism, minimal hepatic or renal clearance, and a terminal half-life of well over five days. That allows an entire week of exposure from one infusion. Some preclinical work suggests better tissue penetration than earlier echinocandins, including into the lung and peritoneum, and it has shown activity against Pneumocystis in animal models, though no clinical claim exists for that indication. It shares the class blind spots: no Cryptococcus, no Mucorales, poor urinary levels.

Targets: Beta-1,3-D-glucan synthase (FKS1), Fungal cell wall

• · 400 mg loading dose on day 1, then 200 mg once weekly. Total therapy is capped at four weekly doses in the label. Approved specifically for adults with limited or no alternative treatment options.

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• commonHypokalaemia— One of the most frequently reported findings in the ReSTORE trial.
• commonPyrexia
• commonDiarrhoea, nausea and vomiting
• commonInfusion-related reactions— Flushing, sensation of warmth, nausea or chest tightness during infusion. Slowing or interrupting the infusion resolves it.
• commonTransaminase elevation
• uncommonPhotosensitivity— Phototoxicity was seen in animal studies and is carried as a labelled warning; sun protection is sensible during therapy.

• Known hypersensitivity to rezafungin or other echinocandins.
• Not active against Cryptococcus, Mucorales or Fusarium.
• The label restricts use to patients with limited or no alternative options — it is not intended as a routine first-choice echinocandin.

• redundantcaspofungin — Same class and target.
• redundantmicafungin — Same class and target; micafungin is cheaper and far more widely stocked.
• cautionCYP substrates — Rezafungin has minimal CYP-mediated metabolism, so significant interactions are few — a modest advantage in polypharmacy.

• · Liver function tests at baseline and periodically.
• · Serum potassium.
• · Follow-up blood cultures until clearance in candidaemia, plus dilated eye examination.
• · Because a dose lasts a week, adverse effects cannot be reversed by stopping — patients need supportive management instead.

Prescription-only injectable, approved in the US and EU for candidaemia and invasive candidiasis in adults with limited or no alternative treatment options.

• Thompson et al. 2023, ReSTORE phase 3 trial of rezafungin versus caspofungin, The Lancet (trial)
• Rezzayo (rezafungin for injection) US prescribing information (label)
• Reviews of rezafungin pharmacokinetics and extended-interval echinocandin dosing (review)

A structurally stabilised echinocandin engineered for a very long half-life, allowing once-weekly intravenous dosing rather than daily. The modification blocks the degradation pathway that limits the older echinocandins, and front-loaded exposure produces high early concentrations that the daily agents cannot match.

The once-weekly schedule is the advantage and the risk: an adverse effect cannot be stopped by withholding the next dose, because the drug is still present for days. The class limitations are unchanged - no Cryptococcus, poor CSF and urinary penetration.

• Beta-1,3-glucan synthase — Non-competitive

  Fungal cell wall synthesis failure

• ReSTORE Phase 3 · n=199 · 2023

  Non-inferior to caspofungin in candidaemia and invasive candidiasis.

High concentrations from the first dose by design, without the ramp of daily agents.

• ?Real-world experience is still limited relative to caspofungin and micafungin, and whether the pharmacokinetic advantage translates into better outcomes is not yet demonstrated.