Chiesi Global Rare Diseases Announces Publication of Results from Phase 3 BALANCE Study in Fabry Disease

- Data published in the Journal of Medical Genetics demonstrate ELFABRIO^® (pegunigalsidase alfa-iwxj) was comparable to agalsidase beta based on the rate of eGFR decline at two years -

BOSTON, January 10, 2024 - Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases, today announced the publication of data from the Phase 3 BALANCE study that demonstrate ELFABRIO^® (pegunigalsidase alfa-iwxj) was generally well tolerated and comparable to agalsidase beta based on estimated glomerular filtration rate (eGFR) decline over two years in adults with Fabry disease with previous agalsidase beta treatment and deteriorating renal function. The results are published in the peer-reviewed Journal of Medical Genetics. 

Pegunigalsidase alfa-iwxj, a PEGylated enzyme replacement therapy (ERT), is a recombinant human α-Galactosidase A enzyme expressed in plant-cell culture. It is approved for the treatment of adults with Fabry disease in the United States, European Union, and Great Britain.

“There continues to be a general lack of awareness and a limited appreciation of the numerous unique challenges that people living with Fabry disease face,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases. “This was the first randomized, double-blind, active-controlled clinical trial of ERTs in Fabry disease, and it would not have been possible without the incredible support from investigators, patients, and families who dedicated two years of their lives to advance this important research. We are pleased to provide patients with Fabry disease an additional treatment option and will continue our work to support millions of people affected by rare diseases around the world.”

The BALANCE study included 77 adults with Fabry disease with an annualized eGFR slope more negative than −2mL/min/1.73m²/year who had received agalsidase beta for at least one year (on average almost six years). Participants were randomized 2:1 to receive 1mg/kg of pegunigalsidase alfa-iwxj or agalsidase beta every two weeks for two years. The primary efficacy analysis assessed annualized rate of change in eGFR differences between treatment arms. The data discussed are not intended to establish that pegunigalsidase alfa-iwxj is better or is not worse than agalsidase beta. Please see the FDA Approval Package available at Drugs@FDA for more information.

At two years, median eGFR slopes were –2.51 mL/min/1.73m²/year for pegunigalsidase alfa-iwxj and –2.16 mL/min/1.73m²/year for agalsidase beta, showing comparability between treatment arms. Overall, pegunigalsidase alfa-iwxj was generally well tolerated, aligning with previous findings in ERT-naïve and other switch patients. Proportions of patients experiencing treatment-emergent adverse events (AEs) and mild or moderate infusion-related reactions were similar in both groups. Exposure-adjusted rates of treatment-emergent AEs and mild or moderate infusion-related reactions were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa-iwxj. At the end of the study, neutralizing antibodies were detected in 15% of pegunigalsidase alfa-iwxj-treated patients and 26% of agalsidase beta-treated patients. The proportion of patients with neutralizing antibodies decreased non-significantly from baseline to study end, from 17/52 (33%) to 7/47 (15%) with pegunigalsidase alfa-iwxj, and from 7/25 (28%) to 6/23 (26%) with agalsidase beta.

“ERTs can lead to clinically relevant improvements in the natural course of Fabry disease, although disease progression occurs in some cases,” said Eric Wallace, M.D., Co-Director of the University of Alabama at Birmingham Fabry Disease Clinic and lead author of the publication. “In the BALANCE study, we evaluated patients with deteriorating renal function. The data demonstrate comparable renal efficacy and the potential for improved tolerability with pegunigalsidase alfa-iwxj compared with agalsidase beta.”

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 an international, research-focused biopharmaceuticals 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), operates in 31 countries, and counts more than 6,500 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 Contact

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

PP-EF-0446 V2.0