PEGASO is an observational study designed to collect prospective data on the effectiveness and safety of pegunigalsidase alfa in adult patients with Fabry disease, being treated or planning to start treatment, under real-world setting.

Start Date01 Apr 2026

Sponsor / Collaborator

Chiesi Ltd.

NCT06328608

/ RecruitingPhase 2/3

Multi-centre, Open-label Trial to Assess the saFety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigaLsidase Alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed FabrY Disease

A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents with Fabry Disease.

Start Date29 Jul 2025

Sponsor / Collaborator

CHIESI Farmaceutici SpA

[+1]

NCT06663358

/ RecruitingNot Applicable

A Multi-Country Observational Study of Safety and Effectiveness of Elfabrio® in Fabry Patients

A multi-centre, multi-country, observational, non-interventional, retrospective and prospective (hybrid) study among Fabry disease participants treated with pegunigalsidase alfa (Elfabrio®) in routine clinical care.

Start Date06 Nov 2024

Sponsor / Collaborator

CHIESI Farmaceutici SpA

100 Clinical Results associated with Pegunigalsidase alfa

100 Translational Medicine associated with Pegunigalsidase alfa

100 Patents (Medical) associated with Pegunigalsidase alfa

Literatures (Medical) associated with Pegunigalsidase alfa

01 Mar 2025·ADVANCES IN THERAPY

Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials

Article

Author: Koulinska, Irene ; Kunduri, Swati ; Raad-Faherty, Angie ; Tremblay, Gabriel ; Poritz, Julia ; Lan, Zhiyi ; Dorling, Patricia ; Azimpour, Khashayar

INTRODUCTION:

Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE). Therefore, the primary objective of this study was to estimate EQ-5D-3L values in clinical trials of pegunigalsidase alfa for FD for future cost-utility analyses.

METHODS:

A mixed effects model was developed to predict values derived from EQ-5D-3L for the following health states used in cost-utility analyses: no Fabry clinical event (FCE)/no pain-related adverse event (AE), pain-related AE, cardiac FCE, cerebrovascular FCE, and renal FCE.

RESULTS:

The baseline EQ-5D-3L utility value had a statistically significant (p < 0.0001) impact on utility values, whereas study, age, sex, disease type, treatment arm, kidney function, and serious AE were not statistically significant. Health state utility values with 95% confidence intervals (CI) for the final model were as follows: no FCE/no pain-related AE, 0.8005 (0.7675, 0.8334); pain-related AE, 0.7737 (0.7262, 0.8211); cardiac FCE, 0.7189 (0.6274, 0.8103); cerebrovascular FCE, 0.7923 (0.6633, 0.9212); and renal FCE, 0.6881 (0.3887, 0.9874).

CONCLUSIONS:

The utility values generated by the present study are generally in line with EQ-5D values in the FD literature and can be used to inform both economic evaluations and our understanding of the impact that FD has on quality of life.

TRIAL REGISTRATION:

NCT03018730, NCT02795676, NCT03180840.

01 Feb 2025·ADVANCES IN THERAPY

Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice

Review

Author: Cianci, Vittoria ; Pieroni, Maurizio ; Mignani, Renzo ; Pisani, Antonio ; Biagini, Elena ; Pieruzzi, Federico ; Tuttolomondo, Antonino

Fabry disease (FD) is a rare lysosomal storage disorder that is characterized by renal, neurological, and cardiovascular dysfunction. Four treatments are currently available for patients with FD; three enzyme replacement therapies (ERTs; agalsidase alfa, agalsidase beta, and pegunigalsidase alfa) and one pharmacological chaperone (migalastat). This review focuses on the evidence for the benefits of ERTs and migalastat, and provides an overview of their impact on disease manifestations and quality of life (QoL). Agalsidase beta is associated with renal, neurological, and cardiovascular benefits, and may prevent renal disease progression. Agalsidase alfa provides stabilizing effects across all main organ systems, although minor sex-specific differences exist in patients with more advanced baseline disease. The benefits of agalsidase alfa and agalsidase beta are similar but depend on the extent of baseline disease. Some data indicate that agalsidase beta may be preferable over the longer term. Both agalsidase alfa and agalsidase beta are associated with improved gastrointestinal and pain symptoms, as well as improved QoL. Patients with advanced end-organ damage tend not to respond as optimally to ERTs as those who initiate ERTs before irreversible organ fibrosis develops, highlighting the need for early treatment initiation. Migalastat, which is only approved for patients with amenable missense gene variants, generally stabilizes renal parameters and provides cardiovascular benefits. Migalastat also improves diarrhea and pain, and stabilizes QoL (although ERT may be more effective for pain management), but the neurological effects of migalastat have not been studied. Real-world data raise concerns about effective in vivo amenability of some genetic variants. Future studies with direct treatment comparisons in patients with FD are needed.

01 Jan 2025·JOURNAL OF INHERITED METABOLIC DISEASE

A phase III, open‐label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies

Article

Author: Rocco, Rossana ; Wallace, Eric ; Almon, Einat Brill ; Warnock, David G. ; Hughes, Derralynn ; Waldek, Stephen ; Longo, Nicola ; Tøndel, Camilla ; Feldt‐Rasmussen, Ulla ; Eyskens, François ; Deegan, Patrick ; Chertkoff, Raul ; Linhart, Aleš ; Alon, Sari ; Wilcox, William R. ; Bernat, John A. ; Pisani, Antonio ; Goker‐Alpan, Ozlem ; Holida, Myrl ; Sakov, Anat

Abstract:

Pegunigalsidase alfa, a PEGylated α‐galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half‐life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open‐label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment‐emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4‐week dosing interval. Thirty‐three of 182 TEAEs (in 9 patients) were considered treatment‐related; all were mild/moderate. No patients developed de novo anti‐drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter‐quartile range) eGFR change from baseline over 52 weeks was −1.9 (−5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: –2.4 [−5.2; 3.2]; females [n = 6]: −0.7 [−9.2; 2.0]). Overall, median eGFR slope was –1.9 (−8.3; 1.9) mL/min/1.73 m2/year (ADA‐negative [n = 20]: −1.2 [−6.4; 2.6]; ADA‐positive [n = 9]: −8.4 [−11.6; –1.0]). Lyso‐Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA‐positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W.

Take‐home message:

Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

112

News (Medical) associated with Pegunigalsidase alfa

06 Feb 2026

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Clear route to registration positions lucerastat as the potential first oral therapy for all patients with Fabry disease

Allschwil, Switzerland – February 06, 2026 Idorsia Ltd (SIX: IDIA) announces the design of its FDA-agreed Phase 3 registration program for lucerastat in Fabry disease. Building on the robust biomarker and renal findings from the MODIFY Phase 3 trial and its long‑term open-label extension (OLE), the program focuses on lucerastat’s impact on renal pathology – a central driver of morbidity and mortality in Fabry disease – with the goal of securing market authorization. Fabry disease is a rare, X-linked lysosomal storage disorder caused by mutations in the GLA gene that lead to deficient α-galactosidase A (α-GalA) activity and progressive accumulation of globotriaosylceramide (Gb3). Over time, Gb3 accumulation drives multisystem organ damage, primarily impacting the kidneys, heart, and nervous system. According to DelveInsight, approximately 16,000 patients were diagnosed with Fabry disease across the seven major markets (US, EU4, UK, Japan) in 2020, a number expected to increase to roughly 21,000 by 2034. The Fabry disease market is projected to reach around USD 4 billion by 2034, underscoring the continued demand for innovative, patient-focused therapies. Srishti Gupta, MD, CEO of Idorsia commented: “This is an important step forward for Idorsia and for the Fabry community. Fabry disease is a serious, progressive condition with a clear need for effective, convenient therapies that address the underlying biology across the full patient population. The strength of our long-term data and a clearly defined regulatory pathway position lucerastat as a uniquely differentiated oral approach. Drug development in Fabry disease is challenging, and meaningful innovation requires both scientific rigor and persistence. With its mutation-independent mechanism and growing body of long-term evidence, we believe lucerastat has the potential to make a real difference for patients.” Registration program agreed with health authorities Idorsia has aligned with the US FDA on a streamlined registration strategy comprising two complementary clinical trials designed to definitively characterize lucerastat’s renal effects. This program is also in line with the feedback received from European Medicines Agency. Pivotal kidney biopsy study (n=16) Adult males with Fabry disease, treatment‑naïve or pseudo‑naïve; Designed to show a decrease from baseline in renal Gb3 burden after 18 months of treatment. Renal function comparative study (n ≈ 74) Adult patients with Fabry disease; Assessment of lucerastat versus established enzyme replacement therapies (agalsidase beta, pegunigalsidase alfa); Designed to reinforce lucerastat as the first oral therapy suitable for all patients with Fabry disease, irrespective of their mutation type. The program is expected to support a potential regulatory filing as early as 2029. Alberto Gimona MD, Head of Global Clinical Development at Idorsia, commented: “The body of evidence we have generated to date shows that long-term treatment with lucerastat consistently reduces the glycosphingolipid substrates that accumulate in Fabry disease. We also observe a slower decline in kidney function compared with patients’ prior historical trajectories. Importantly, kidney biopsy data from long-term treated patients demonstrate low-to-no levels of characteristic lysosomal deposits. Following constructive discussions with health authorities, we have agreed on the trials that will form the basis for establishing substantial evidence of effectiveness in support of a future NDA and MAA. The agreed program includes a pivotal baseline-controlled biopsy study and a second study which will then show that an oral treatment can potentially achieve a similar effect to today’s cumbersome standard-of-care.” About the MODIFY study ( NCT03425539 ) and OLE ( NCT03737214 ) MODIFY was a multicenter, double-blind, randomized, placebo-controlled, Phase 3 study evaluating lucerastat as an oral monotherapy for adults with Fabry disease. A total of 118 patients from 14 countries were randomized 2:1 to lucerastat or placebo. Upon completion of the double-blind period, 107 patients entered a long-term OLE assessing safety, tolerability, and renal outcomes. Primary results from MODIFY and the 12-month interim OLE analysis have been published in Nature Communications , (“ Lucerastat, an oral therapy for Fabry disease: Results from a pivotal phase 3 study and its open-label extension ”, January 2026). While the MODIFY study did not meet its primary endpoint of reducing neuropathic pain over six months, lucerastat demonstrated a robust pharmacodynamic effect, significantly reducing plasma and urinary Gb3 levels compared to placebo. These reductions were sustained over time in the OLE, with patients switching from placebo to lucerastat showing similar biomarker reductions. More importantly, as presented at WORLD Symposium ™ 2026 , an interim analysis of the OLE, where ongoing patients had been treated with lucerastat for at least 42 months – some exceeding six years of continuous therapy – revealed a notable shift in renal function trajectory. Treatment with lucerastat was associated with a reduction in the rate of eGFR decline as compared to eGFR slope observed in the 2 years preceding their enrollment in MODIFY (eGFR slope, historical: -3.50; Lucerastat: -1.64). Lucerastat treatment was also associated with a particularly marked attenuation of kidney function loss in patients with severe disease course, such as classic males with Fabry disease (historical: -4.32; Lucerastat: -2.05), patients with impaired renal function at baseline (eGFR <90 mL/min/1.73m 2 ) (historical: -6.18; Lucerastat: -2.49), Anti-Drug Antibody (ADA+) positive patients (historical: -7.75; Lucerastat: -3.43). The effect was independent of the gene variants’ amenability to migalastat. Lucerastat also led to a 51% decrease in plasma Gb3 levels and was well-tolerated with long-term treatment. In addition, the positive impact on kidney function was supported by a kidney biopsy sub-study of six male adult patients with classic Fabry disease who had received lucerastat monotherapy for a median treatment period of 56 months. The study evaluated the number of kidney Gb3 inclusions using established quantitative (Barisoni Lipid Inclusion Scoring System (BLISS)) and semi-quantitative (Fabrazyme Scoring System (FSS)) methodologies. At enrollment in MODIFY, 4 participants were ERT naïve or pseudo-naïve and 2 switched from ERT. Median kidney Gb3 BLISS score was 1.7 (range: 0.7–4.5; mean (SD): 2.41 (1.59)). Mean FSS scores were 0 indicative of “no or trace” accumulation (5/6 participants) or 1 indicative of mild accumulation (1/6). The 2 patients who switched from ERT had BLISS scores of 1.6-1.8 and a FSS score of 0. The results indicate that long-term treatment with lucerastat monotherapy was associated with low-to-no levels of kidney Gb3 inclusions. Notes to the editor About Fabry disease Fabry disease is a rare, X-linked lysosomal storage disorder caused by mutations in the GLA gene that results in the absence or markedly reduced activity of the enzyme α-galactosidase A (α-GalA). α-GalA normally breaks down a fatty product known as globotriaosylceramide (Gb3) in the cells of the body. Deficiency over time results in an accumulation of Gb3 deposits throughout the body, leading to multisystem disease, mainly affecting the kidneys, heart, and nervous system. The disease manifests in two main phenotypes: classic Fabry disease, typically presenting in childhood with severe, multisystemic involvement, and late-onset Fabry disease, which may emerge in adulthood with predominant cardiac or renal symptoms. Fabry disease affect a patient’s life expectancy and quality of life. Due to its variable presentation and non-specific symptoms, Fabry disease is frequently underdiagnosed or misdiagnosed, leading to delays in treatment and increased risk of irreversible organ damage. As the gene responsible for Fabry disease is found on the X chromosome (of which males have one, and females two), males with deleterious mutations have little or no residual alpha-GalA activity. Therefore, these male patients with Fabry disease experience a wider spectrum of symptoms, and in some cases, a greater severity. It is now widely accepted that women with Fabry disease are heterogeneous with respect to disease severity and may sometimes also develop life threatening complications of the disorder. Up to 70% of female carriers develop Fabry related symptoms at some point in their life. Current treatment options include enzyme replacement therapies (ERTs) and oral chaperone therapy for patients with amenable mutations. However, these therapies have limitations, including intravenous administration, immunogenicity, and mutation-specific efficacy. There remains a significant unmet need for a well-tolerated, oral, disease-modifying therapy that can be used regardless of genotype or prior treatment history. Lucerastat in Fabry disease Lucerastat is an investigational, oral substrate reduction therapy designed to treat Fabry disease independently of α-Gal A activity, GLA mutation status, or prior enzyme replacement therapy (ERT). It acts by inhibiting glucosylceramide synthase, thereby reducing the synthesis of glycosphingolipids, including globotriaosylceramide (Gb3), which accumulate due to deficient α-galactosidase A activity in Fabry disease. Preclinical studies demonstrated that lucerastat is a highly soluble and bioavailable small molecule capable of penetrating key tissues affected by Fabry disease – including the kidneys, liver, and dorsal root ganglia – where it effectively reduces substrate accumulation. Clinical pharmacology studies confirmed lucerastat’s favorable pharmacokinetic profile, characterized by rapid absorption, predictable elimination, and no evidence of saturation, supporting consistent exposure across dosing regimens. Across Phase 1 studies, lucerastat was well tolerated at doses up to 4000 mg, with no dose-limiting toxicities and a safety pro by concomitant medications. In a 12-week exploratory study in adult Fabry patients receiving ERT, lucerastat 1000 mg twice daily led to a rapid and sustained reduction in plasma Gb3 and related biomarkers, confirming its mechanism of action and potential for fast-onset substrate reduction. The recently published Phase 3 MODIFY study and its long-term extension further support lucerastat’s disease-modifying potential. While the primary endpoint of neuropathic pain reduction was not met, lucerastat demonstrated robust and sustained biomarker reductions and a promising renal signal, with a slower rate of eGFR decline in patients with impaired kidney function. These findings suggest lucerastat may offer long-term organ protection and broaden therapeutic options for Fabry patients, especially those underserved by current treatments. Key Literature Wallace E., et al. Lucerastat effect on kidney function in patients with Fabry disease: Results from the ongoing open label-extension (OLE) of the phase 3 clinical program. Mol Genet Metab. 2026;147(2):109659. Germain DP., et al. Lucerastat, an investigational oral substrate reduction therapy in Fabry disease: Kidney biopsy results from the MODIFY open-label extension study. Mol Genet Metab. 2026;147(2):109423. Nordbeck P., et al. Lucerastat, an oral therapy for Fabry disease: Results from a pivotal phase 3 study and its open-label extension. Nature Communications, 10 January 2026 (online ahead of print). Guérard N., et al. Lucerastat, an iminosugar for substrate reduction therapy: tolerability, pharmacodynamics, and pharmacokinetics in patients with Fabry disease on enzyme replacement. Clin Pharmacol Ther. 2018; 103(4):703-11. Welford RWD., et al. Glucosylceramide synthase inhibition with lucerastat lowers globotriaosylceramide and lysosome staining in cultured fibroblasts from Fabry patients with different mutation types. Hum Mol Genet 2018; 27(19): 3392-3403 Germain DP. Fabry disease. Orphanet J Rare Dis. 2010 Nov 22;5:30. About Idorsia The purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA). For further information, please contact: George Thampy Senior Vice President, Head of Investor Relations Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil +41 58 844 10 10 investor.relations@idorsia.com – media.relations@idorsia.com – The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as “intend”, "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs, business development activities and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

Clinical ResultPhase 3

05 Feb 2026

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Chiesi Global Rare Diseases Reinforces Long-Term Commitment to the Rare Disease Community with Multiple Abstract Presentations at the 22nd Annual WORLDSymposium™

-- Chiesi’s abstract presentations will focus on clinical insights and patient-reported outcomes in Fabry disease and alpha-mannosidosis -- -- These scientific contributions in lysosomal storage disorders (LSDs) underscore a sustained investment in data generation, patient-centered research, and authentic rare disease representation -- BOSTON, Feb. 05, 2026 (GLOBE NEWSWIRE) -- 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 presentations at the 22 nd Annual WORLD Symposium™ , held February 2-6, 2026, in San Diego, California. The company is proud to support 16 scientific abstracts across Fabry disease and alpha-mannosidosis, including 11 Chiesi‑led presentations and 5 Chiesi-supported independent studies. These abstracts reinforce the Company’s long-term commitment to people with lysosomal storage disorders (LSDs) and the rare disease community. The presentations detail clinical insights, including long-term data up to 10 years from the Phase 3 extension study (BRILLIANCE) for Fabry disease, 1 and patient and caregiver-reported outcomes, reflecting Chiesi’s belief that meaningful progress in rare diseases must integrate robust data with the lived experiences of patients and caregivers. “Innovation requires sustained scientific rigor, responsible research and development, and continuity of commitment. That is why we are incredibly proud to participate in, and share our findings at, the annual WORLD Symposium , a meeting with global collaboration dedicated to meaningful advancements for the LSD community,” said Rachele Berria, MD, PhD, Senior Vice President, Head of Global Medical Affairs. “Our programs, partnerships, products, and pipeline represent comprehensive care that spans the entire patient journey. From advanced diagnosis all the way through to long-term quality-of-life outcomes, we believe patient perspectives should actively guide every step of the development process. By deeply integrating robust clinical insights with the vital voices of patients and caregivers, we aim to advance truly transformative solutions and models of care that aim to significantly improve the lives of those with rare diseases and their families.” These 16 abstracts, including one late-breaker and two platform presentations, span a broad range of topics and reflect the depth of Chiesi’s research and engagement. Presentations include new clinical and real-world data on Fabry disease, as well as an expanded understanding of alpha-mannosidosis, including insights into diagnosis and caregiver impact and quality-of-life outcomes across the patient journey. Together, these presentations reinforce Chiesi’s long-standing commitment to people living with rare diseases, supported by a patient-focused communications approach used across Chiesi Global Rare Diseases’ work. This approach will also be reflected in Chiesi’s presence at the WORLDSymposium, including in the presentation “ True Faces of Rare: Authenticity Over Aesthetics – Shaping a New Visual Language for Fabry and Other Rare Disease Communications ,” which formalizes the Company’s use of real patient imagery and lived experience in rare disease communications. “In rare conditions, accuracy matters not only in science, but in how these diseases are visually represented,” said Stuart Siedman, Vice President, Patient Advocacy, Chiesi Global Rare Diseases . “With True Faces of Rare, we are affirming a simple but powerful principle: patients deserve to be seen as they truly are. Authenticity is not an aesthetic choice; it is a reflection of respect, trust, and responsibility toward the communities we serve.” The WORLDSymposium represents an important moment of scientific exchange for the LSD community, and a checkpoint in Chiesi’s long-term journey across LSDs, with continued investment in data, collaboration, and patient-centered progress ahead. About Fabry Disease Fabry disease is a rare, inherited lysosomal storage disorder caused by mutations in the GLA gene, which leads to a deficiency of the enzyme alpha-galactosidase A. This deficiency results in an accumulation of a fatty substance called globotriaosylceramide (GL-3) in the body’s cells, affecting the heart, kidneys, skin, nervous system, and other organs. 2 Fabry disease can cause a range of serious signs and symptoms, including fatigue, chronic pain, gastrointestinal issues, decreased ability to sweat, progressive kidney failure, heart complications, and increased risk of stroke. 3 The condition affects both males and females and can present from childhood through adulthood, often with delayed diagnosis or misdiagnosis. While Fabry disease is rare, early detection and access to appropriate treatment — such as enzyme replacement therapy or pharmacological chaperone therapy — are critical in managing symptoms and slowing disease progression. 2 About Alpha-mannosidosis Alpha-mannosidosis is an ultra-rare, inherited lysosomal storage disorder caused by mutations in the MAN2B1 gene, which results in a deficiency of the enzyme alpha-mannosidase. 4 This deficiency leads to the accumulation of oligosaccharides, within the body’s cells, causing progressive damage to multiple organs and tissues. 5 Alpha-mannosidosis can affect the musculo-skeletal system, hearing, immune system, nervous system, and other organs, and is associated with a wide range of signs and symptoms, including skeletal abnormalities, impaired mobility, hearing loss, cognitive impairment, immune dysfunction, and behavioral or mental health challenges. 4 The condition affects both children and adults and may present with few or mild symptoms early in life, progressing over time as oligosaccharides accumulate. 4,5 While alpha-mannosidosis is rare, timely diagnosis and appropriate disease management are important to help address symptoms and support long-term outcomes for affected individuals. 4 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, France and Colombia, Chiesi’s commitment to creating shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, Chiesi is 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 90 years of experience, Chiesi is headquartered in Parma (Italy), with 31 affiliates worldwide, and counts more than 7,500 employees. The Group’s research and development center in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. 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 living with rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have 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. Chiesi Global Rare Diseases Media Contact Sky Striar LifeSci Communications Email: sstriar@lifescicomms.com References 1) Germain, D. P., & Linhart, A. (2024). Pegunigalsidase alfa: a novel, pegylated recombinant alpha-galactosidase enzyme for the treatment of Fabry disease. Frontiers in genetics , 15, 1395287. 2) Mehta, A., & Hughes, D. A. (2024). Fabry disease . In M. P. Adam, S. Bick, G.M. Mirzaa, et al. (Eds.), GeneReviews ® . University of Washington, Seattle. 3) Cleveland Clinic. (2025, October 9). Fabry disease: Symptoms & causes . 4) Malm, D., & Nilssen, Ø. (2008). Alpha-mannosidosis. Orphanet journal of rare diseases , 3, 21. 5) Borgwardt, L., Stensland, H. M., Olsen, K. J., Wibrand, F., Klenow, H. B., Beck, M., Amraoui, Y., Arash, L., Fogh, J., Nilssen, Ø., Dali, C. I., & Lund, A. M. (2015). Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet journal of rare diseases , 10 , 70.

Phase 3

01 Feb 2026

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Chiesi Global Rare Diseases and Protalix BioTherapeutics Receive Positive CHMP Opinion for an Additional Dosing Regimen of 2mg/kg Body Weight Every-Four-Weeks for Elfabrio® (pegunigalsidase alfa) ▼ in the EU

Committee for Medicinal Products for Human Use (CHMP) issues a positive opinion following re-examination, which will be reviewed by the European Commission (EC), with a decision anticipated by March 2026 If approved by the EC, this dosing regimen would reduce the burden to eligible adult patients, their families and the broader healthcare system due to the current requirement to visit infusion centres or have home infusions every-2-weeks for treatment PARMA, Italy and CARMIEL, Israel, Jan. 30, 2026 (GLOBE NEWSWIRE) -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, and Protalix BioTherapeutics, Inc. (NYSE American: PLX), a biopharmaceutical company focused on the discovery, development, production and commercialization of innovative therapeutics for rare diseases with significant unmet needs, today announced an update on pegunigalsidase alfa. The Committee for Medicinal Product for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval of the 2mg/kg every-4-weeks (E4W) dosing regimen for pegunigalsidase alfa in Fabry disease adult patients stable with an enzyme replacement therapy. This positive opinion follows the CHMP’s re-examination of the company’s application for the additional dosing regimen. “It is our privilege to provide the adult Fabry community with an alternative dosing option, and we are pleased that the CHMP positive opinion supporting a 2mg/kg body weight E4W dosing regimen for pegunigalsidase alfa brings us one step forward to reducing the treatment burden in this condition,” said Giacomo Chiesi, Executive Vice President, Chiesi Global Rare Diseases . “We’re focused on evolving treatments based on real-world needs, so that people living with Fabry disease have not just the right care, but care that fits into their lives. By extending the time between infusions, our aim is that people living with this condition can focus on what truly matters, living their lives.” “The CHMP’s positive opinion is another testament to Protalix’s commitment to advancing treatments for people living with Fabry disease and, together with Chiesi, we are grateful to all of the patients and investigators and their staff members who participated in our clinical trial programs," said Dror Bashan, President and Chief Executive Officer of Protalix . “The CHMP’s positive opinion is a significant validation of Protalix’s proprietary ProCellEx® manufacturing platform, built on years of rigorous research and clinical progress.” “The CHMP positive opinion on the E4W regimen recognizes the importance of reducing treatment burden for people living with Fabry and their families,” said Mary Pavlou, President, Fabry International Network (FIN) . “Extending infusion intervals allows therapy to better fit into everyday life, supporting work, study, and family commitments. This step reflects care that adapts to real life and respects the priorities of those who live with the disease.” The CHMP opinion is informed by results from an open-label, switch-over study, BRIGHT (formally PB-102-F50), designed to assess the adverse event profile, efficacy, and pharmacokinetics (PK) of the alternative dosing regimen of pegunigalsidase alfa 2 mg/kg E4W for 52 weeks, 1 and its ongoing open-label extension study CLI-06657AA1-03 (formerly PB-102-F51). 2 Protalix will be eligible to receive a regulatory milestone payment of $25 million from Chiesi if the E4W dosing regimen is approved by the EC. About Fabry Disease Fabry disease is a rare, inherited lysosomal storage disorder caused by mutations in the GLA gene, which leads to a deficiency of the enzyme alpha-galactosidase A. This deficiency results in an accumulation of a fatty substance called globotriaosylceramide (GL-3) in the body’s cells, affecting the heart, kidneys, skin, nervous system, and other organs. 3 Fabry disease can cause a range of serious signs and symptoms, including fatigue, chronic pain, gastrointestinal issues, decreased ability to sweat, progressive kidney failure, heart complications, and increased risk of stroke. 4 The condition affects both males and females and can present from childhood through adulthood, often with delayed diagnosis or misdiagnosis. While Fabry disease is rare, early detection and access to appropriate treatment — such as enzyme replacement therapy or pharmacological chaperones — are critical in managing symptoms and slowing disease progression. 3 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, France and Colombia, Chiesi’s commitment to creating shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, Chiesi is 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 90 years of experience, Chiesi is headquartered in Parma (Italy), with 31 affiliates worldwide, and counts more than 7,500 employees. The Group’s research and development center in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. 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 living with rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have 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. About Protalix BioTherapeutics, Inc. Protalix is a biopharmaceutical company focused on the discovery, development, production and commercialization of innovative therapeutics for rare diseases. Protalix has researched, developed and currently manufactures two enzyme replacement therapies that are currently available in multiple markets. These therapies are recombinant therapeutic proteins expressed through Protalix’ s proprietary plant cell-based expression system, ProCellEx ® . ProCellEx is a unique plant cell-based system that enables Protalix to produce recombinant proteins in an industrial-scale manner with no exposure to mammalian cells. Protalix is the first company to gain U.S. Food and Drug Administration (FDA) approval of a protein produced through plant cell-based in suspension expression system. Protalix has licensed to Pfizer Inc. the worldwide development and commercialization rights to taliglucerase alfa, Elelyso ® , for the treatment of Gaucher disease, excluding in Brazil, where Protalix retains full rights. Protalix has partnered with Chiesi Farmaceutici S.p.A. for the global development and commercialization of pegunigalsidase alfa, which was approved by both the FDA and the EMA in May 2023. Protalix’ s development pipeline includes, among others, two proprietary versions of recombinant therapeutic proteins that target established pharmaceutical markets: PRX–115, a plant cell-expressed recombinant PEGylated uricase for the treatment of uncontrolled gout; and PRX–119, a plant cell-expressed long acting DNase I for the treatment of NETs-related diseases. Protalix BioTherapeutics, Inc. Forward-Looking Statements To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. The terms “anticipate,” “believe,” “estimate,” “expect,” “can,” “continue,” “could,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and other words or phrases of similar import are intended to identify forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk and the final results of a clinical trial may be different than the preliminary findings for the clinical trial. Factors that might cause material differences include, among others: the risk that the EC will not approve the CHMP’s positive opinion recommending approval of the 2mg/kg E4W dosing regimen for pegunigalsidase alfa in adults with Fabry disease; risks related to the commercialization of pegunigalsidase alfa; risks relating to pegunigalsidase alfa market acceptance, competition, reimbursement and regulatory actions, including as a result of the boxed warning contained in the FDA approval received for the product; delays in the approval or potential rejection of any applications filed with the FDA, EMA or other health regulatory authorities for Protalix' s product candidates, and other risks relating to the review process; the risk that the results of clinical trials will not support the applicable claims of safety or efficacy; ; risks relating to changes to published interim, topline or preliminary data from clinical trials; the inherent risks and uncertainties in developing drug platforms and products of the type we are developing; the impact of development of competing therapies and/or technologies by other companies; and risks relating to changes in healthcare laws, rules and regulations in the United States or elsewhere; and other factors described in our filings with the U.S. Securities and Exchange Commission. The statements in this press release are valid only as of the date hereof and Protalix disclaims any obligation to update this information, except as may be required by law. Chiesi Global Rare Diseases Media Contact Sky Striar LifeSci Communications Email: sstriar@lifescicomms.com Protalix BioTherapeutics, Inc. Investor Contact Mike Moyer, Managing Director LifeSci Advisors +1-617-308-4306 mmoyer@lifesciadvisors.com References 1) Holida, M, et al., (2024). A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme. Journal of Inherited Metabolic Disease. doi:10.1002/jimd.12795. 2) Bernat et al., (2025). Extending the interval between pegunigalsidase alfa infusions in patients with Fabry disease: five-year interim results from the ongoing BRIGHT51 study Abstract presented at ICIEM Congress 2025 . 3) Mehta, A., & Hughes, D. A. (2024). Fabry disease . In M. P. Adam, S. Bick, G.M. Mirzaa, et al. (Eds.), GeneReviews ® . University of Washington, Seattle. 4) Cleveland Clinic. (2025, October 9). Fabry disease: Symptoms & causes .

Phase 3Drug Approval

100 Deals associated with Pegunigalsidase alfa

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KEGG	Wiki	ATC	Drug Bank
D11685	-	-	DB14992

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Approved

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Indication	Country/Location	Organization	Date
Fabry Disease	European Union	CHIESI Farmaceutici SpA	04 May 2023
Fabry Disease	Iceland	CHIESI Farmaceutici SpA	04 May 2023
Fabry Disease	Liechtenstein	CHIESI Farmaceutici SpA	04 May 2023
Fabry Disease	Norway	CHIESI Farmaceutici SpA	04 May 2023

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Indication	Highest Phase	Country/Location	Organization	Date
Myocardial Infarction	Phase 2	United Kingdom	Protalix Ltd.	21 Feb 2013
Stroke	Phase 2	United Kingdom	Protalix Ltd.	21 Feb 2013

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02795676 (BALANCE, Pubmed \| J Med Genet)	Phase 3	Fabry Disease lyso-Gb3 concentrations	-	Pegunigalsidase alfa 1 mg/kg	roulgaocoe(gcmmbepiye) = wynbzgqsae efytwbujsg (rqvnzrltjf )	Positive	01 Jun 2024
				Agalsidase beta 1 mg/kg	roulgaocoe(gcmmbepiye) = yjaccglxld efytwbujsg (rqvnzrltjf )
NCT02795676 (BALANCE, PRNewswire) Manual	Phase 3	Fabry Disease	77	pegunigalsidase alfa-iwxj	ovtukprnkx(zwtoyppqwz) = tluazxbnhy aoebjjvvku (uiafczhgum ) View more	Positive	10 Jan 2024
				agalsidase beta	ovtukprnkx(zwtoyppqwz) = rkadrmqrfw aoebjjvvku (uiafczhgum ) View more
NCT03018730 (BRIDGE, Pubmed \| Orphanet J Rare Dis)	Phase 3	Fabry Disease plasma lyso-Gb3 level	-	Pegunigalsidase alfa 1 mg/kg	hmodlhdhcj(pbpgmedfjf) = 35% out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline uwpqyatgmw (yokvlhbuir ) View more	Positive	21 Oct 2023
SSIEM2023	Not Applicable	-	142	Pegunigalsidase alfa	vtchzglzka(bbehuutopu) = 25% of pts had an IRR plzkenduqg (nvbzpoaonl ) View more	-	30 Aug 2023
SSIEM2023	Not Applicable	-	113	Pegunigalsidase alfa 1 mg/kg every other week	izocuwtbqw(iexycrdgsx) = vsoskkpqjp aidvqtnkce (sefqujfjxs ) View more	-	30 Aug 2023
				Pegunigalsidase alfa 2 mg/kg every 4 weeks	izocuwtbqw(iexycrdgsx) = hyuiyfgafb aidvqtnkce (sefqujfjxs ) View more
NCT02795676 (BALANCE study \| BALANCE, CTgov)	Phase 3	Fabry Disease	78	PRX-102 (pegunigalsidase alfa) (PRX-102 (Pegunigalsidase Alfa))	njtfcvzfdz(ghwajlvsxp) = zctvkvcgux kfqbcwpizt (kjmblypqpj, mydwubabry - dveobmkqqj) View more	-	02 Aug 2023
				agalsidase beta (Agalsidase Beta)	njtfcvzfdz(ghwajlvsxp) = eybvnoqozc kfqbcwpizt (kjmblypqpj, gkddmbdkwm - auduijjzqh) View more
NCT01678898 (FDA) Manual	Phase 1/2	Fabry Disease	14	ELFABRIO	rzxdfmdnue(zccengehrq) = djwnwshsjy icojsnuhyd (aturtqldev ) View more	Positive	09 May 2023
				ELFABRIO (Males)	rzxdfmdnue(zccengehrq) = frkboqmhkq icojsnuhyd (aturtqldev ) View more
NCT03566017 (FDA) Manual	Phase 3	Fabry Disease	77	ELFABRIO	ybigwqgbhd(xnrqjmxgtw) = dhbpbgjqwg obygsaqjrr (vdhhqhrizr ) View more	Positive	09 May 2023
				agalsidase beta	ybigwqgbhd(xnrqjmxgtw) = qujgrkczfl obygsaqjrr (vdhhqhrizr )
EMA Manual	Phase 1/2	Fabry Disease	13	Elfabrio	btbjjrbhbn(tciwflzaky) = qqxlvgeupi azbuadqabc (mqkzemajce ) View more	Positive	08 May 2023
NCT03180840 (BRIGHT, SSIEM2022)	Phase 3	Fabry Disease Maintenance α-galactosidase A	30	Pegunigalsidase alfa 2.0 mg/kg	baijqwhbav(ccfbbeaeqj) = ifjjmztqon wdtbfyoywt (ubkbbnilih )	Positive	30 Aug 2022

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