Chiesi Global Rare Diseases Announces Publication of Results from Phase 3 BRIGHT Study of ELFABRIO® (pegunigalsidase alfa-iwxj) in Fabry Disease

- Data published in Journal of Inherited Metabolic Disease

CARY, N.C., October 28, 2024 – Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the publication of results from the Phase 3 BRIGHT study of ELFABRIO^® (pegunigalsidase alfa-iwxj) 2 mg/kg administered every four weeks for 52 weeks in adult patients with Fabry disease who were previously treated with agalsidase alfa or beta administered every two weeks. The approved dose of ELFABRIO is 1mg/kg every two weeks. The regimen of ELFABRIO 2mg/kg administered every four weeks is investigational and not approved by the FDA.

“We are pleased to share that the Journal of Inherited Metabolic Disease has published these data from this Phase 3, open-label, multinational, switchover study evaluating the pharmacokinetics, safety and efficacy of 2 mg/kg ELFABRIO administered every four weeks,” said Giacomo Chiesi, executive vice president of Chiesi Global Rare Diseases. “Chiesi is committed to evaluating additional evidence to confirm the long-term results of this administration schedule.”  

ELFABRIO is a PEGylated α-Gal A enzyme replacement therapy (ERT) that is approved for the treatment of adults with Fabry disease in the United States, European Union and Great Britian. The approved dose of ELFABRIO is 1mg/kg every two weeks.

A total of 29 patients (23 men, 6 women) completed the Phase 3 open-label, single arm, switchover, 12-month BRIGHT study. Results from the Phase 3 BRIGHT study showed:

• Pegunigalsidase alfa median plasma concentration at the end of each 4-week dosing interval was above the lower limit of quantification
• There were no new safety concerns among patients treated with ELFABRIO
  • 9/30 (30%) patients treated with ELFABRIO experienced at least one treatment-related adverse event (TRAE), all of which were mild or moderate
  • 5/30 (16.7%) patients experienced at least one infusion-related reaction, all of which were mild or moderate
  • No patients developed de novo anti-drug antibodies (ADAs) or treatment-emergent AEs leading to study discontinuation or mortality
• Median estimated glomerular filtration rate (eGFR) remained stable in the efficacy population, with change from baseline of -1.9 mL/min/1.73m²/year (-2.4 in males, -0.7 in females) after 12 months of treatment with ELFABRIO
• Plasma globotriaosylsphingosine (lyso-Gb3) concentrations were low and stable in women treated with ELFABRIO (0/6 ADA-positive), with a slight increase observed in treated men (9/24 ADA-positive) compared to baseline
  
  

“While the trial enrolled patients with heterogeneous clinical manifestations who were followed for only 12 months, results show that 2 mg/kg  pegunigalsidase alfa administered every four weeks is generally well-tolerated in stable adult ERT-experienced patients with Fabry disease and that this schedule deserves further exploration through additional research,” said John Bernat, M.D., Ph.D., Clinical Associate Professor of Pediatrics-Medical Genetics and Genomics, University of Iowa Health Care, lead author of the publication. “An open label extension trial is ongoing and  will provide additional data on this investigational treatment regimen.”

“Fabry disease today is witnessing the surge of innovative research into diverse treatments, which is a new dawn of hope rising on the horizon,” said Jack Johnson, Co-founder, Executive Director, Fabry Disease Support & Information Group, and Vice President, Americas & Global, Fabry International Network.

For more information on this study please see the following link.

Indication and Important Safety Information for Elfabrio^® (pegunigalsidase alfa-iwxj) 

Indication 

Elfabrio^® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. 

Important Safety Information 

Prior to Elfabrio administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions (IARs) and instruct them to seek medical care immediately if such symptoms occur.  

• If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Elfabrio administration and initiate appropriate medical treatment. 
• If a mild to moderate hypersensitivity reaction or IAR occurs, consider slowing the infusion rate or temporarily withholding the dose. 
   

In clinical trials, 20 (14%) Elfabrio-treated patients experienced hypersensitivity reactions.  

Four Elfabrio-treated patients (3%) experienced anaphylaxis reactions that occurred within 5 to 40 minutes of the start of the initial infusion. The signs and symptoms of hypersensitivity reactions and anaphylaxis included headache, nausea, vomiting, throat tightness, facial and oral edema, truncal rash, tachycardia, hypotension, rigors, urticaria, intense pruritus, moderate upper airway obstructions, macroglossia, and mild lip edema. 

In clinical trials, 41 (29%) Elfabrio-treated patients experienced one or more infusion-associated reactions, including hypersensitivity, nausea, chills, pruritus, rash, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension.  

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitor serum creatinine and urinary protein-to-creatinine ratio. If glomerulonephritis is suspected, discontinue treatment until a diagnostic evaluation can be conducted. 

When switching to Elfabrio from a prior enzyme replacement therapy, the risk of hypersensitivity reactions and infusion-associated reactions may be increased in certain patients with pre-existing anti-drug antibodies (ADAs). Consider monitoring IgG and IgE ADAs and clinical or pharmacodynamic response (eg, plasma lyso-Gb3 levels). 

The most common adverse reactions (≥15%) were infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis. 
 
Please see Full Prescribing Information for Elfabrio. 

About Chiesi Global Rare Diseases
Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system.

For more information visit www.chiesirarediseases.com.

About Chiesi Group
Chiesi is a research-oriented international biopharmaceutical group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment.

By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi’s commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we’re part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035.

With over 85 years of experience, Chiesi is headquartered in Parma (Italy), with 31 affiliates worldwide, and counts more than 7,000 employees. The Group’s research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden.

For further information please visit www.chiesi.com.

Chiesi Group Media Contacts

Chiara Travagin
Head of Communications, Rare Diseases
Tel: +39 348 8818985
Email: c.travagin@chiesi.com

Adam Daley
Berry & Company Public Relations
Tel: +1 212 253 8881
Email: adaley@berrypr.com

 

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