Elfabrio (pegunigalsidase alfa-iwxj) / Protalix, Chiesi - LARVOL DELTA

Maternal and Postnatal Outcomes Study (MOS): A Global Observational Registry Assessing the Safety of Elfabrio® in Women With Fabry Disease and Their Infants During Pregnancy and Breastfeeding (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Fabry Disease • Genetic Disorders

Chiesi Global Rare Diseases and Protalix BioTherapeutics Announce European Commission Approval of Additional Dosing Regimen of Every Four Weeks for Elfabrio (pegunigalsidase alfa) (Protalix Press Release) - "The EC approval 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, and its ongoing open-label extension study CLI-06657AA1-03 (formerly PB-102-F51)."

EMA approval • Fabry Disease

PEGASO: Observational Study on Long-term Use of Pegunigalsidase Alfa in Fabry Patients in a Real-world Setting (clinicaltrials.gov) - P=N/A | N=75 | Not yet recruiting | Sponsor: Chiesi Italia | Initiation date: Jan 2026 ➔ Apr 2026

Real-world evidence • Trial initiation date • Fabry Disease • Genetic Disorders

Long-Term Safety and Efficacy of Pegunigalsidase Alfa in Patients with Fabry Disease: Results from the Phase 3 BRILLIANCE Extension Study (ACMG 2026) - P3 | "At baseline, most participants had received enzyme replacement therapy (71.1% agalsidase beta; 18.6% agalsidase alfa); 25.8% had anti-drug antibodies (ADAs) against PA, and median (range) baseline estimated glomerular filtration rate (eGFR) was 77.7 (24.4, 131.0) mL/min/1.73m². These findings demonstrate that long-term treatment with pegunigalsidase alfa 1 mg/kg E2W offers a sustained safety and efficacy profile in adults with FD over a median of nearly six years, supporting its role as a viable long-term therapy."

Clinical • P3 data • Fabry Disease • Genetic Disorders

A rapid method to reduce drug interferences for antibody measurements in pegunigalsidase alfa-treated patients with Fabry disease. (PubMed, Front Immunol) - "Alkaline pretreatment with NaOH was sufficient to eliminate up to 1 µg/ml agalsidase alfa or pegunigalsidase alfa in control sera. A second patient with pre-existing ADAs before pegunigalsidase alfa-initiation showed a massive induction of anti-PEG antibodies with inhibitory function. We present a rapid alkaline-treatment based method to overcome drug interferences to measure at least free antibodies in patients treated with pegunigalsidase alfa."

Journal • Fabry Disease • Genetic Disorders

Chiesi Global Rare Diseases and Protalix BioTherapeutics Receive Positive CHMP Opinion for an Additional Dosing Regimen of Every Four Weeks for Elfabrio (pegunigalsidase alfa) in the EU (The Manila Times) - "The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion following re-examination, which will be reviewed by the European Commission (EC), with a decision anticipated by March 2026....The CHMP opinion is based on results from an open-label, switch-over study, BRIGHT (formally PB-102-F50), designed to assess the safety, efficacy, and pharmacokinetics (PK) of the new dosing regimen of pegunigalsidase alfa 2 mg/kg E4W for 52 weeks, and its ongoing open-label extension study CLI-06657AA1-03 (formerly PB-102-F51, with a median exposure of almost 6 years). Further support is provided by an updated Population Pharmacokinetics (PopPK) model and exposure-response analysis, which leverage data from multiple clinical studies."

CHMP • Fabry Disease

Bright51: Open Label Extension of 2 mg/kg Pegunigalsidase Alfa (PRX-102) Every 4 Weeks in Adult Fabry Disease Patients (clinicaltrials.gov) - P3 | N=29 | Active, not recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Trial completion date: Mar 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Fabry Disease • Genetic Disorders

Lysosomal storage diseases in North America: a comprehensive review of enzyme therapies and unmet needs. (PubMed, Ther Adv Rare Dis) - "Newer formulations such as pegunigalsidase (Elfabrio®) use for FD (Fabry disease), exhibit lower affinity for developing ADA compared to other ERTs, offer reduced immunogenicity and safety profiles enhancement...This review draws from MEDLINE, Cochrane Reviews, and PubMed (1984-2025) using search terms such as LSDs, ERTs, rare diseases, Gaucher disease, Fabry disease, and others. Ongoing research and health policy reforms are essential to improve access, equity, and therapeutic outcomes for patients with LSDs."

Journal • Review • Fabry Disease • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Chiesi Global Rare Diseases Announces Health Canada Approval of Elfabrio (pegunigalsidase alfa) for Fabry Disease (GlobeNewswire) - "Health Canada’s approval is supported by a comprehensive clinical development program, which evaluated the safety, tolerability, and efficacy of Elfabrio in more than 140 patients with up to 7.5 years of follow-up treatment."

Canada approval • Fabry Disease

RISE: Study to Evaluate the Safety, PK, PD, and Efficacy of PRX-102 in Japanese Patients With Fabry Disease (clinicaltrials.gov) - P2/3 | N=16 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Trial completion date: Mar 2028 ➔ Aug 2029 | Trial primary completion date: Mar 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Fabry Disease • Genetic Disorders

Impact of PEGylated COVID-19 vaccination on patient tolerability to pegunigalsidase alfa – a new PEGylated enzyme replacement therapy for Fabry disease (SSIEM 2023) - P3 | "Infusion-related reactions (IRRs) and anti-PEG antibodies were assessed from first infusion and post-vaccination (based on PEGLNP COVID-19 vaccine [tozinameran, Pfizer-BioNTech; mRNA-1273, Moderna] approval, patients treated with PA between Dec 1, 2020 to study end or data cutoff were analyzed). PEGLNP vaccines (eg, COVID-19 mRNA vaccines), do not appear to increase the risk of IRRs or anti-PEG antibodies in PA-treated patients. PA is a well-tolerated ERT for patients with FD."

Clinical • Fabry Disease • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease

Cost-Utility Analysis of Pegunigalsidase Alfa Compared to Agalsidase Alfa and Agalsidase Beta for the Treatment of Adult Patients With Fabry Disease in Greece (ISPOR-EU 2025) - "Enzyme replacement therapies (ERT) (agalsidase-alfa, agalsidase-beta, pegunigalsidase-alfa), along with migalastat have shown clinical benefits; however, their economic value remains a key consideration for payers. Treatment with pegunigalsidase-alfa results in less costs and potentially improves health outcomes compared to currently used ERTs for adult patients with FD in Greece."

Clinical • HEOR • Fabry Disease • Genetic Disorders • Rare Diseases

Matching-Adjusted Indirect Comparisons (MAICs) and Network Meta-Analyses (NMAs) of the Oral Small-Molecule Chaperone Migalastat vs. Intravenous Enzyme Replacement Therapies (ERTs) for Clinical Measures in Fabry Disease (ISPOR-EU 2025) - P1/2, P3 | "OBJECTIVES: ATTRACT (NCT01218659) compared migalastat with ERT (agalsidase alfa/beta [AGAL-α/β]) in patients with Fabry disease and amenable GLA variants. We indirectly compared migalastat with pegunigalsidase alfa (PEG) for key cardiac/renal measures and with any ERT for long-term risk of Fabry-associated clinical events (FACEs; specific cardiac/renal/cerebrovascular events/death). Systematic/targeted literature reviews identified publications/studies reporting left ventricular mass index (LVMi), annualised change in estimated glomerular filtration rate (eGFR slope) and/or FACEs... In populations matched for age, sex, eGFR/previous ERT duration and ACEi/ARB, LVMi change and eGFR slope were similar for migalastat and PEG; long-term FACE risk was similar for migalastat and AGAL-α/β."

Clinical • Fabry Disease • Genetic Disorders

Pegunigalsidase Alfa Elfabrio® as a Long-Term Enzyme Replacement Therapy in Adults With Fabry Disease: A Systematic Literature Review (ISPOR-EU 2025) - P1/2, P3 | "Pegunigalsidase alfa demonstrated improved efficacy and a comparable safety profile to agalsidase beta, supporting its long-term use in adults with Fabry disease but further research is warranted to assess its comparative effectiveness versus agalsidase alfa."

Clinical • Review • Fabry Disease • Genetic Disorders

What Has Worked Well in Fabry Disease? An HTA Landscape Assessment Study (ISPOR-EU 2025) - "These submissions were assessed for the final recommendations for reimbursement and key issues. We found four treatments for FD, including agalsidase alfa, agalsidase beta, pegunigalsidase alfa, and migalastat. This analysis suggests that HTA journey of treatments in FD has been challenging and inconsistent, with most HTA receiving conditional recommendations. While orphan medications address medical needs for a small number of patients and their development should be encouraged, HTA agencies mainly assess it from economic value in addition to the clinical benefits over the existing standard care."

Fabry Disease • Genetic Disorders • Rare Diseases

Pooled analysis of the effect of pegunigalsidase alfa on renal function: Data from 113 patients in the pegunigalsidase alfa clinical trial program (SSIEM 2023) - No abstract available

Retrospective data

Safety and tolerability of pegunigalsidase alfa: Insights from a single site experience from the Expanded Access Program in the United States (SSIEM 2023) - No abstract available

Clinical

Pooled safety profile of pegunigalsidase alfa: an analysis of data from 142 patients in the pegunigalsidase alfa clinical program (SSIEM 2023) - No abstract available

Clinical

Impact of PEGylated COVID-19 vaccination on patient tolerability to pegunigalsidase alfa – a new PEGylated enzyme replacement therapy for Fabry disease (SSIEM 2023) - No abstract available

Clinical • Fabry Disease • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease

Pooled analysis of the effect of pegunigalsidase alfa on renal function: Data from 113 patients in the pegunigalsidase alfa clinical trial program (SSIEM 2023) - No abstract available

Retrospective data

Safety and tolerability of pegunigalsidase alfa: Insights from a single site experience from the Expanded Access Program in the United States (SSIEM 2023) - No abstract available

Clinical

Pooled safety profile of pegunigalsidase alfa: an analysis of data from 142 patients in the pegunigalsidase alfa clinical program (SSIEM 2023) - No abstract available

Clinical

Impact of PEGylated COVID-19 vaccination on patient tolerability to pegunigalsidase alfa – a new PEGylated enzyme replacement therapy for Fabry disease (SSIEM 2023) - No abstract available

Clinical • Fabry Disease • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease

Pooled analysis of the effect of pegunigalsidase alfa on renal function: Data from 113 patients in the pegunigalsidase alfa clinical trial program (SSIEM 2023) - No abstract available

Retrospective data

Safety and tolerability of pegunigalsidase alfa: Insights from a single site experience from the Expanded Access Program in the United States (SSIEM 2023) - No abstract available

Clinical