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CUVRIOR Efficacy

CHELATE Trial Efficacy Results 1
CUVRIOR displayed non-inferiority vs. D-penicillamine (DPA) in the first trientine head-to-head prospective, randomized, phase III CHELATE trial

PATIENTS

Aged 18 - 75 with stable Wilson Disease (N=53)

STUDY TREATMENT

Randomized to either continue DPA maintenance dose, or be switched to CUVRIOR

PRIMARY ENDPOINT

Measurement of free copper by non-ceruloplasmin-bound (NCC) assay at 28 weeks

OUTCOMES

  • Mean difference at 28-weeks in serum NCC was -9.1 µg/L (95% Cl: - 24.2 to +6.1)
  • A higher proportion of patients remained within the target urinary copper excretion range vs. DPA
  • Masked ("blinded") clinical adjudication of stability assessed by three independent clinicians confirmed clinical stability in all study participants at 24- and 48-weeks
  • There were no notable changes in either Clinical Global Impressions of Change of Unified Wilson Disease Rating Scale neurological assessment from baseline (pre-randomized) at weeks 24 and 48)
Figure adapted from Schilsky et al, 2022 1
TRIUMPH Trial Efficacy Results 2
CUVRIOR demonstrated a predictable pharmacokinetic profile, fast absorption, and improved bioavailability vs. trientine dihydrochloride in the randomized, single-center, crossover TRIUMPH trial
Figure adapted from Weiss et al, 20212

*3 participants withdrew prematurely from the study due to personal reasons.

STUDY POPULATION

Healthy volunteers aged 18-45 years (N=26)*

STUDY TREATMENT

Randomized to either receive CUVRIOR (TETA 4HCl) or TETA 2HCl (trientine dihydrochloride)

OUTCOMES

  • Median time to reach Cmax were 2 and 3 hours for CUVRIOR and TETA 2HCl, respectively
  • The rate and extent of absorption of trientine were greater for CUVRIOR than TETA 2HCl (≈ 68% and 56%, respectively)

References:

  1. Schilsky M L, et al. Lancet Gastroenterol Hepatol. 2022;7(12):1092-1102.
  2. Weiss K H, et al. Eur J Drug Metab Pharmacokinet. 2021;46(5):665-675.

Indication & Important Safety Information

CUVRIOR is a copper chelator indicated for the treatment of adult patients with stable Wilson Disease who are de-coppered and tolerant to penicillamine. Please see full Prescribing Information.
Important Safety Information
INDICATION
CUVRIOR is a copper chelator indicated for the treatment of adult patients with stable Wilson Disease who are de-coppered and tolerant to penicillamine.
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • CUVRIOR is contraindicated in patients with hypersensitivity to trientine or to any of the excipients in CUVRIOR.

WARNINGS AND PRECAUTIONS

  • Potential for Worsening of Clinical Symptoms at Initiation of Therapy, including neurological deterioration, may occur at the beginning of CUVRIOR therapy due to mobilization of excess stores of copper. Adjust the dosage or discontinue therapy if clinical condition worsens. Evaluate serum non-ceruloplasmin copper (NCC) levels or 24-hour urinary copper excretion (UCE) when initiating treatment, after 3 months, and approximately every 6 months thereafter.
  • Copper Deficiency may develop following treatment with CUVRIOR. Periodic monitoring is required.
  • Iron Deficiency may develop following treatment with CUVRIOR. If iron deficiency develops, a short course of iron supplementation may be given.
  • Hypersensitivity Reactions, characterized by rash, have been reported with the use of trientine. Rash was reported in 12% (3/26) of CUVRIOR-treated patients, and one patient discontinued treatment due to rash. If rash or other hypersensitivity reaction occurs, consider discontinuing CUVRIOR.

ADVERSE REACTIONS

The most common adverse reactions (>5%) are abdominal pain, change of bowel habits, rash, alopecia, and mood swings.

DRUG INTERACTIONS

  • Mineral Supplements (e.g. iron, zinc, calcium, magnesium): Avoid concomitant use. If concomitant use is unavoidable, take CUVRIOR at least 2 hours before or 2 hours after iron and take CUVRIOR at least 1 hour before or 2 hours after other mineral supplements.
  • Other Drugs for Oral Administration: Take CUVRIOR at least 1 hour apart from any other oral drug

Please see full Prescribing Information

To report SUSPECTED ADVERSE REACTIONS, call Orphalan at 1-800-961-8320 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch