Orphalan announces FDA acceptance for filing of New Drug Application (NDA) for trientine tetrahydrochloride (TETA 4HCl) for the treatment of Wilson’s Disease

Orphalan announces FDA acceptance for filing of New Drug Application (NDA) for trientine tetrahydrochloride (TETA 4HCl) for the treatment of Wilson’s Disease

• NDA supported by positive data fromPhase 3 CHELATE clinical trial
• TETA 4-HCl previously granted Orphan Drug Designation for first-line treatment of Wilson’s Disease

Paris, France – 2 September 2021 – Orphalan SA, a Company that identifies, develops and delivers worldwide therapies for orphan diseases, today announces that the US Food and Drug Administration (FDA) has accepted for review the Company’s New Drug Application (NDA) for trientine tetrahydrochloride (TETA 4HCl) for the first-line treatment of Wilson’s Disease.

Wilson’s Disease is a rare inherited disorder of copper transport primarily affecting the liver and brain, affecting about 1 in every 30,000 people worldwide. TETA 4HCl is proposed as an alternative copper chelating agent to d-Penicillamine, the only approved first-line treatment of Wilson’s Disease for the last 70 years, to which about a third of patients develop intolerance.

The Company’s NDA submission follows its previous Orphan Drug Designation by the FDA. The filing is based upon positive data from the CHELATE Phase 3 clinical trial that met its primary efficacy endpoint by demonstrating that TETA 4HCl was non-inferior to d-Penicillamine as measured by copper speciation evaluation of non-ceruloplasmin copper (NCC).

Treatment with TETA 4HCl is supported by Orphalan’s novel NCC assay, for which the Company plans to file for FDA approval as a companion diagnostic. The in vitro NCC assay has the potential to provide an important additional tool to support physicians in identifying patients and monitoring their treatment with TETA 4HCl.

Dr Naseem Amin, Chief Executive Officer at Orphalan, commented:“The FDA’s acceptance of the NDA brings us one step closer toproviding first-line treatment to patients with Wilson’s Disease,who currently do not benefit from alternativemethods of treatment, beyond D-Penicillamine ”.

- ENDS -

Notes to Editors

About the CHELATE Study

CHELATE was 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. Trientine tetrahydrochloride was well tolerated and during treatment, more patients achieved the pre-specified composite endpoint of NCC and 24-hour Urinary Copper Excretion (UCE) within therapeutic target ranges, compared to patients treated with d-Penicillamine, 50% versus 24%. Data from the trial was presented during an oral presentation at EASL’s The International Liver Congress™ 2021.

About Orphalan
At Orphalan, our mission is clear: we are pioneers in orphan diseases. Orphalan identifies, develops and delivers worldwide innovative therapies for people living with Orphan diseases. Orphalan was founded in 2011 and has launched Cuprior™ across Europe with its own commercial organisation. For more information, visit www.orphalan.health and follow us on LinkedIn.

For more information, please contact:

Orphalan
Tel: +33 (0)1 42 49 82 64
info@orphalan.health

Consilium Strategic Communications:
Mary-Jane Elliott, Allison Connolly, Genevieve Wilson
Tel: +44 (0) 203 709 5700
orphalan@consilium-comms.com