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

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

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) - "The safety and efficacy of PA has been investigated in 4 clinical trials and 3 long-term extensions, consisting of ERT-naïve patients (pts) and those who switched from agalsidase beta (AB) or alfa (AA). In this pooled analysis that included a large proportion of pts with prior ERT exposure, PA- treated pts showed slower decline in eGFR over time, indicating that PA can be a valuable option for FD, regardless of gender or prior ERT exposure."

Retrospective data • Fabry Disease • Genetic Disorders

Safety and tolerability of pegunigalsidase alfa: Insights from a single site experience from the Expanded Access Program in the United States (SSIEM 2023) - P | "The enrollment reasons included poor tolerability of agalsidase beta (AB), disease progression on AB, and worsening of proteinuria on migalastat...One ERT-naïve male with classic FD enrolled due to poor tolerability with venglustat and withdrew after experiencing a serious adverse event (SAE) of hypersensitivity reaction with the third PA infusion (antidrug antibody [ADA]-negative at baseline [BL])... PA is a novel ERT that is well tolerated in patients with FD. While healthcare providers should remain vigilant for possible hypersensitivity reactions, PA may offer the benefit of reduced infusion duration and lower premedication burden for some patients with poor tolerability with other ERTs."

Clinical • Cardiovascular • Fabry Disease • Genetic Disorders • Immunology • Movement Disorders • Renal Disease • Ventricular Tachycardia

Pooled safety profile of pegunigalsidase alfa: an analysis of data from 142 patients in the pegunigalsidase alfa clinical program (SSIEM 2023) - "This pooled analysis showed PA had an overall favourable safety profile and was well-tolerated by pts with FD. TEAE and IRR rates were low, and events were mostly mild/moderate and occurred irrespective of prior ERT treatment. Premedication use decreased over time among “switchers.”"

Clinical • Fabry Disease • Genetic Disorders

Chiesi Global Rare Diseases and Protalix Biotherapeutics Acknowledge CHMP Negative Opinion on Every Four Week Dosing Regimen of Elfabrio (pegunigalsidase alfa) in the EU (The Manila Times) - "The submission for CHMP review was based on data from an open-label, switch-over trial, BRIGHT (formally PB-102-F50), designed to assess the safety, efficacy and pharmacokinetics (PK) of pegunigalsidase alfa 2 mg/kg administered every four weeks and its ongoing open label extension study, CLI-06657AA1-03 (formerly PB-102-F51)....These data were not deemed sufficient to conclude on similar efficacy. Chiesi and Protalix intend to keep working together to support the Fabry disease community."

CHMP • Fabry Disease

FLY: A Study to Learn About the Safety and Effects of the Study Drug PRX-102 in Children and Adolescents With Fabry Disease (clinicaltrials.gov) - P2/3 | N=22 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Trial completion date: Mar 2028 ➔ Apr 2031 | Trial primary completion date: Dec 2027 ➔ Oct 2028

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

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

New trial • Real-world evidence • Fabry Disease • Genetic Disorders

Clinical Efficacy and Real-World Effectiveness of Fabry Disease Treatments: A Systematic Literature Review. (PubMed, J Clin Med) - "Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta stabilized renal function and cardiac structure in patients with Fabry disease...Patients treated with migalastat and pegunigalsidase alfa also maintained stable renal function and cardiac structure. Overall, current treatments slow the progression of renal and cardiac decline in patients with Fabry disease. Large cohort studies with long-term follow-up and baseline stratification based on clinical phenotype are needed to address evidence gaps and provide clinicians with robust data to inform treatment decisions."

Journal • Real-world evidence • Review • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases