Paris, France. June 25 (Korea Bizwire) — Orphalan SA is a company that identifies, develops and delivers innovative treatments to patients with rare diseases. Orphalan today announced positive top line results from a phase 3 head-to-head trial comparing d-Penicillamine with trientine tetrahydrochloride in Wilson’s Disease (WD). The phase 3 trial has been completed through an IND program for FDA submission. Wilson’s Disease is a rare inherited disorder of copper transport primarily affecting the liver and brain. Untreated, this is a fatal disease.
The CHELATE trial is the first prospective randomised trial comparing d-Penicillamine with trientine tetrahydrochloride. D- Penicillamine has been the only approved first line treatment for the last 70 years. Trientine tetrahydrochloride if approved has the potential to be used as maintenance therapy in patients with Wilson’s Disease.
The CHELATE trial met its primary efficacy endpoint by demonstrating that trientine tetrahydrochloride was non-inferior to d-Penicillamine as measured by copper speciation evaluation of non-ceruloplasmin copper (NCC). This novel analytical method was developed by Orphalan through consultation with the FDA. The pre-specified composite endpoint of non-ceruloplasmin copper (NCC) and 24-hour urinary copper excretion (UCE), was achieved by 50% of patients treated with trientine tetrahydrochloride versus 24% of patients treated with d-Penicillamine.
Five serious adverse events (SAEs) were observed in the 27 patients treated with d-Penicillamine, while no SAEs were observed in the 26 patients randomised to trientine tetrahydrochloride. Treatment emergent adverse events (TEAEs) temporally related to the study treatments reported in the study were comparable in both groups and were graded as either mild or moderate and transitory in nature.
The data arising from this study will be presented at EASL’s International Liver Congress today at 8.45 CEST and will be submitted for publication. Analysis of the 48-week data from the CHELATE Phase 3 investigational study is ongoing and will be presented at a future scientific forum.
“With a chronic disorder like Wilson’s Disease, interrupting or stopping treatment for any reason can provoke the return of disease activity, sometimes with severe consequences. Physicians and patients should work together to choose a medication that provides the right balance of efficacy, safety and tolerability to help manage patients’ Wilson’s Disease and meet their treatment goals,” said Dr. Michael Schilsky , Principal Investigator and Professor of Medicine and Director of the Center for Excellence for Wilson Disease at Yale University. “These top-line results suggest that trientine tetrahydrochloride offers a differentiated tolerability profile and represents a safe and effective alternative to d-Penicillamine as a maintenance therapy for patients with Wilson’s Disease.”
“Despite its poor safety profile, d-Penicillamine is the only approved first line therapy in Wilson’s Disease. The CHELATE study showed that patients on d-Penicillamine can be safely switched to trientine tetrahydrochloride, without compromising efficacy. Our commitment to this study is in line with our strategy to provide robust clinical data to physicians to enable them to make evidence-based treatment decisions.” said Dr. Naseem Amin, Chief Executive Officer at Orphalan. He added: “The clinical evidence from this trial and the use of the novel assay for NCC developed by Orphalan have the potential to make a meaningful difference to the patient’s life and the physician’s ability to monitor their disease.”
Notes to Editors
About the CHELATE Study
CHELATE is a Phase 3, multicentre, randomised, open label, active-controlled, non-inferiority study conducted in 9 countries at 15 centres designed to evaluate efficacy and safety of trientine tetrahydrochloride compared to d-Penicillamine in patients with stable Wilson’s Disease. Fifty-three adult Wilson’s Disease patients with clinically stable disease for over one year and who met specific inclusion criteria, including laboratory measures of serum non-ceruloplasmin copper (NCC), 24-hour urinary copper excretion (UCE) and liver function tests, were followed for a baseline period for 12 weeks before being randomised 1:1 to either trientine tetrahydrochloride or d-Penicillamine twice daily. The study’s primary endpoint was serum NCC as measured using Orphalan’s proprietary method using copper speciation at 24-weeks post-randomisation. A secondary composite efficacy endpoint was NCC and 24-hour UCE.
Additional secondary endpoints included were: clinical Global Impression of Change (CGIC) score; serum copper and ceruloplasmin levels; the unified Wilson’s Disease Rating Scale (UWDRS); modified Nazer score; cognitive assessments and standard safety assessments. In addition, an independent adjudication committee blinded to the allocated treatment, and study centres assessed key efficacy and safety parameters to determine clinical stability of the patient.
About Trientine Tetrahydrochloride
Trientine tetrahydrochloride is an investigational, novel oral trientine formulation with Orphan Drug Designation under development through a 505(b)(2) pathway for the treatment of Wilson’s Disease maintenance patients. The trientine tetrahydrochloride NDA is planned to be submitted mid-year 2021. If approved by the FDA, Orphalan intends to market trientine tetrahydrochloride itself in the US.
About the Trientine Tetrahydrochloride Clinical Development Program
The key components of the clinical development program of trientine tetrahydrochloride include the CHELATE trial, a Phase 3, open-label, six-month safety and efficacy study in maintenance Wilson’s Disease patients, along with pharmacokinetic bridging studies comparing trientine tetrahydrochloride to two formulations of trientine dihydrochloride, Triumph I and Triumph 2. The CHELATE clinical development program also includes the CHELATE extension phase, assessing the safety, efficacy and tolerability of trientine tetrahydrochloride and d-Penicillamine over a period of 1 year.
Cuprior™ is a form of trientine tetrahydrochloride which is approved in the EU for patients intolerant to d-Penicillamine. Of the estimated 5,000 diagnosed Wilson’s Disease patients in the EU, we estimate 25% are considered intolerant.
Cuprior™ is contraindicated in patients hypersensitive to trientine.
Cuprior™ is a registered and unregistered trademark of Orphalan.
For important safety information and full prescribing information, including patient information for Cuprior™ please visit https://www.cuprior.com
Trientine tetrahydrochloride is under investigation and not approved for use in any indication in the United States.
At Orphalan, our mission is clear: we are pioneers in orphan diseases. Orphalan is a company that identifies, develops and delivers innovative treatments to patients with rare diseases. Orphalan was founded in 2011 and has launched Cuprior™ across Europe with its own commercial organisation.
Contact for Orphalan:
Tel : +33 (0)1 42 49 82 64
Contact For Media:
Consilium Strategic Communications:
Mary-Jane Elliott, Allison Connolly
Tel: +44 (0) 203 709 5700
Source: Orphalan via GLOBE NEWSIWRE