CuvriorTM (trientine tetrahydrochloride) is a copper-chelating agent prescribed for the treatment of adult patients with stable Wilson disease who are de-coppered and penicillamine-tolerant.1 Wilson disease is a rare genetic disease in which the body is unable to excrete excess copper, so that it accumulates in the liver, brain, eyes, and other organs. High copper levels harm organs, and Wilson disease can be fatal if left untreated.2 Cuvrior is available as oral tablets containing 300 mg of trientine tetrahydrochloride, which is equivalent to 150 mg of trientine.3 

For adult patients, a total daily dose of Cuvrior of 300 to 3000 mg taken orally in divided doses (2 times daily) is advised. The maximum recommended daily dose is 3000 mg.1 

Cuvrior was newly approved by the US Food and Drug Administration (FDA) on May 2, 2022. The drug is manufactured by Orphalan, an international orphan drug development and commercialization company. Cuvrior will be available in the United States by early 2023.4

Cuvrior must be taken on an empty stomach, at a minimum of 1 hour before or 2 hours after a meal, and at least 1 hour apart from any other drug, food, or milk. The tablets should be swallowed whole with water and should not be crushed, chewed, or dissolved.1

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Cuvrior (Trientine Tetrahydrochloride)
Cuvrior (Trientine Tetrahydrochloride) Credit: PubChem

Mechanism of Action

Cuvrior contains trientine, a copper-chelating agent that clears the body of absorbed copper by forming a stable complex that is subsequently excreted through the urine. Additionally, trientine reduces the absorption of copper by chelating copper in the intestinal tract.5 Cuvrior can be used only by patients with Wilson disease whose copper levels are under control and who can take penicillamine.6 

Efficacy in Trials and Trial Results

The FDA approval of Cuvrior was based on results from the randomized, open-label phase 3 CHELATE STUDY trial (NCT03539952), which compared the safety and efficacy of Cuvrior with those of penicillamine in 53 adults with Wilson disease. All patients had been using penicillamine for at least 1 year before enrollment in the trial, and they were all adequately managed and able to tolerate the medication. During a baseline phase of 12 weeks at the beginning of the study, patients continued to take their prescribed daily dose of penicillamine. They were then randomly allocated at week 12 either to continue penicillamine or to switch to Cuvrior for the following 24 weeks. By showing that Cuvrior was non-inferior to penicillamine as determined by copper speciation evaluation of non-ceruloplasmin copper (NCC), this study met its primary effectiveness endpoint. The pre-specified composite endpoint of NCC and 24-hour urinary copper excretion (UCE) was attained by 50% of the patients who received Cuvrior and 24% of those who received penicillamine.1,5

Warnings, Precautions, and Adverse Effects

Cuvrior has the potential to worsen clinical symptoms at the start of therapy, including neurological problems. It is important for patients to inform their physician if this occurs so that the dose can be adjusted or the medication discontinued entirely. Copper levels must be evaluated at the start of treatment, after 3 months, and then every 6 months.6 

Copper deficiency may develop following therapy with Cuvrior. If the patient’s copper requirements change, such as during pregnancy, when copper levels must be carefully regulated to support proper growth and mental development, close monitoring for signs of copper insufficiency is necessary.6

Iron deficiency may also develop following therapy with Cuvrior, particularly in menstruating or pregnant women or as a result of the low-copper diet suggested for patients with Wilson disease. Patients may suffer from dizziness, confusion, feeling tired, muscle weakness, or tingling in hands or feet due to low copper or iron levels.6 Patients are otherwise advised not to take mineral supplements like iron, zinc, calcium, and magnesium while undergoing treatment with Cuvrior because absorption of the drug can be reduced. If it is necessary to take these supplements concomitantly with Cuvrior, then Cuvrior should be taken at least 2 hours before or 2 hours after iron. Cuvrior should be taken at least 1 hour before or 2 hours after other mineral supplements.1 

Hypersensitivity reactions, characterized by rash, have been frequently reported as a side effect of Cuvrior in clinical studies. In case a rash or any other allergic reaction develops during treatment with Cuvrior, it is important that patients discuss with their doctor whether to continue taking it or switch to a different drug.1 

The most common adverse effects noted (>5% of cases) are abdominal pain, changes in bowel habits, rash, hair loss, and mood swings. Other side effects include iron deficiency anemia, lupus, muscle damage, and muscle spasm. Some of the adverse reactions identified during post approval use of trientine hydrochloride are rhabdomyolysis, colitis, dystonia, and myasthenia gravis. These reactions were reported voluntarily from a population of uncertain size.1,6 

References

  1. CuvriorTM (trientine tetrahydrochloride) tablets, for oral use. Highlights of prescribing information. Orphalan; 2022. Accessed September 15, 2022.
  2. FDA approves Orphalan’s Cuvrior™ (trientine tetrahydrochloride), the first treatment for Wilson’s disease in over five decades. News release. Cision PR; May 4, 2022.
  3. Cunha JP. Cuvrior. Rxlist. Updated May 11, 2022. Accessed September 13, 2022.
  4. Orphalan announces FDA approval of Cuvrior™ for the treatment of adult patients with stable Wilson’s disease who are de-coppered and tolerant to penicillamine. News release. Orphalan; May 2, 2022.
  5. Cuvrior (trientine tetrahydrochloride) tablets. wcg CenterWatch. Accessed  September 15, 2022.
  6. Hannemann K. Cuvrior (trientine tetrahydrochloride). GoodRx. Updated June 2, 2022. Accessed  September 15, 2022.

Reviewed by Debjyoti Talukdar, MD, on 9/26/2022.

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