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

- Data published in the Orphanet Journal of Rare Diseases demonstrate safety and efficacy of pegunigalsidase alfa-iwxj in patients previously treated with agalsidase alfa -

BOSTON, March , 27, 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 BRIDGE study that evaluated the safety and efficacy of ELFABRIO (pegunigalsidase alfa-iwxj) in patients with Fabry disease who were previously treated with agalsidase alfa. The data are published in the Orphanet Journal of Rare Diseases.

“We are pleased to share a new peer-reviewed publication that continues to build on the comprehensive data set we have collected on treatment with pegunigalsidase alfa-iwxj in adults living with Fabry disease,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases. “Our goal is to offer a safe and effective treatment option for this rare disease community, because while much progress has been made in the treatment of Fabry disease, there are still important unmet needs. We are continuing our work to make this treatment option available to Fabry disease patients around the world.”

Pegunigalsidase alfa-iwxj 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 United Kingdom.

A total of 20 patients completed the Phase 3 open-label, switch-over BRIDGE study that was designed to assess the safety and efficacy of 12 months of treatment with pegunigalsidase alfa-iwxj (1 mg/kg every two weeks) in adults with Fabry disease who had been previously treated with agalsidase alfa (0.2 mg/kg every two weeks) for at least two years. Safety findings show treatment with pegunigalsidase alfa-iwxj was generally well-tolerated, with most (97%) treatment-emergent adverse events (TEAEs) being of mild or moderate severity. Before switching to pegunigalsidase alfa-iwxj, mean (standard error) annualized estimated glomerular filtration rate (eGFR) slope was −5.90 (1.34) mL/min/1.73 m²/year. Twelve months post-switch, the mean eGFR slope was −1.19 (1.77) mL/min/1.73 m²/year, and mean plasma lyso-Gb3 reduced by 31%.

Seven of the study participants tested positive for antidrug antibodies (ADAs) at least once during the study. Of the seven participants who were ADA-positive, three had transient responses and returned to ADA-negative status during the study. Mean (standard error) changes in eGFR slope for ADA-positive and ADA-negative patients were +5.47 (3.03) and +4.29 (3.15) mL/min/1.73 m²/year, respectively.

This study’s main limitation was the uncontrolled period of agalsidase alfa treatment before the pre-switch study period. An additional limitation was the lack of data on plasma Gb3 and lyso-Gb3 before initiation of agalsidase alfa, allowing to compare only reductions achieved by pegunigalsidase alfa-iwxj treatment to levels that were likely already reduced from previous treatment. Lastly, the trial was not designed to assess whether the efficacy findings are due to the PEGylated structure of pegunigalsidase alfa-iwxj or to the administration of a higher dose relative to agalsidase alfa as per each product’s approved dosage of 1 mg/kg versus 0.2 mg/kg, respectively.

Agalsidase alfa is approved for administration with a dosage of 0.2mg/kg in Canada and the European Union. Agalsidase alfa has not been evaluated by the U.S. Food and Drug Administration (FDA), therefore it is not FDA approved.

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 Contacts

Chiara Travagin
Rare Communication Manager
Tel: +39 348 8818985
Email: c.travagin@chiesi.com

Alessio Pappagallo
Press Office Manager
Tel: +39 339 5897483
Email: a.pappagallo@chiesi.com

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

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