Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)

Dosage and administration details:

pegunigalsidase alfa individual dose for each patient was prepared according to the patient's weight. Pegunigalsidase alfa administrated at 1 mg/kg, intravenously over 3 hours, every 2 weeks. After the first 2 months of treatment with pegunigalsidase alfa, infusion time may be reduced gradually to 1.5 hours pending patient tolerability.

• PRX-102 (pegunigalsidase alfa) (Biological), also known as pegunigalsidase alfa, Recombinant human alpha galactosidase-A: PRX-102 1 mg/kg every 2 weeks

Primary outcomes

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 [12 months]: Results represent the number of treatment-emergent adverse events (TEAE) that were considered possibly, probably, or definitely related to treatment

Other outcomes

• eGFR [Baseline and Month 12 (week 52)]: eGFR was calculated based on the serum creatinine values that were assessed at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 according to the CKD-EPI formula, baseline and Month 12 (week 52) reported. The absolute change in eGFR from baseline measurement at visit 1 prior to first PRX-102 infusion to last measurement at Month 12 was summarized using descriptive statistics.
• Mean Annualised Change in eGFR (Slope) [Pre-switch, Post-switch]: The annualized change in eGFR (slope) per patient was calculated with all available eGFR values using a linear regression. The mean pre-switch slope is the eGFR slope during screening period and pre-infusion visit 1 (while on Replagal®). The mean post-switch slope is the eGFR slope during PRX-102 treatment, calculated based on eGFR vales at weeks 4, 8, 12, 16, 20, 26, 30, 34, 38, 42, 46, 52 after visit 1. The mean change in eGFR slope from pre- to post-switch is the mean difference between the two slopes. eGFR was calculated based on the serum creatinine values according to the CKD-EPI formula.
• Plasma Lyso-Gb3 [Baseline and month 12 (week 52)]: Plasma Lyso-Gb3 is Fabry disease specific biomarker that can assess treatment outcome which was measured at Baseline and weeks 12, 26, 38, 52. Baseline and Month 12 (week 52) reported.
• Number of Participants According to Protein/Creatinine Ratio (UPCR) [12 months]: Urine Protein to Creatinine Ratio (UPCR), assessed by spot urine test, at Month 12 (Week 52).Number of Participants According to Protein/Creatinine Ratio (UPCR) level
• Left Ventricular Mass Index (g/m^2) by MRI [12 months]: Left ventricular mass was determined based on cardiac MRI data and the LVMI was indexed to patient's body surface area (g/m\^2). In male patients the normal range for LVMI was 57-91 g/m\^2, in female patients 47-77 g/m\^2.
• Quality of Life EQ VAS [12 months]: The EQ VAS, of the EQ 5D 5L questionnaire, records the subject's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (score "100") and 'Worst imaginable health state' (score "0").

Sex: All, ages: 18 Years to 60 Years

Inclusion Criteria:

1. Age: 18-60 years
2. A documented diagnosis of Fabry disease
3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to laboratory range and one or more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata iii. Clustered angiokeratoma
4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata iii. Clustered angiokeratoma
5. Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80% labelled dose/kg) for at least 6 months
6. eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation
7. Availability of at least 2 historical serum creatinine evaluations since starting agalsidase alfa treatment and not more than 2 years
8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method

Exclusion Criteria:

1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa
2. History of renal dialysis or transplantation
3. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy)
4. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
5. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
6. Known history of hypersensitivity to Gadolinium contrast agent that was not managed by the use of premedication;
7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding
8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before screening
9. Congestive heart failure NYHA Class IV
10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before screening
11. Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Monitor would interfere with the patient's compliance with the requirements of the study

Participant flow

Outcome results

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 (Primary), Number, participants: PRX-102 21
• eGFR (Other pre specified), Mean, mL/min/1.73m^2: PRX-102 Efficacy Population 79.46 +/- 4.92; PRX-102 Male 75.87 +/- 6.62; PRX-102 Female 86.14 +/- 6.72
• Mean Annualised Change in eGFR (Slope) (Other pre specified), Mean, mL/min/1.73m^2/year: PRX-102 Efficacy Population -5.9 +/- 1.34; PRX-102 Male -6.36 +/- 1.89; PRX-102 Female -5.03 +/- 1.65
• Plasma Lyso-Gb3 (Other pre specified), Mean, nM: PRX-102 Efficacy Population 38.51 +/- 9.68; PRX-102 Male 51.81 +/- 13.60; PRX-102 Female 13.81 +/- 2.31
• Number of Participants According to Protein/Creatinine Ratio (UPCR) (Other pre specified), Number, Subjects: PRX-102 Efficacy Population 9; PRX-102 Male 7; PRX-102 Female 2
• Left Ventricular Mass Index (g/m^2) by MRI (Other pre specified), Mean, g/m^2: PRX-102 Efficacy Population 86.9 +/- 6.9; PRX-102 Male 97.6 +/- 8.9; PRX-102 Female 66.9 +/- 5.8
• Quality of Life EQ VAS (Other pre specified), Mean, Score: PRX-102 Efficacy Population 71.8 +/- 4.3; PRX-102 Male 66.8 +/- 5.3; PRX-102 Female 81.6 +/- 6.1

Adverse events

Time frame: 12 months

Serious adverse events by term

Other adverse events by term

• Results publication: Azimpour K, Dorling P, Koulinska I, Kunduri S, Lan Z, Poritz J, Tremblay G, Raad-Faherty A. Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials. Adv Ther. 2025 Mar;42(3):1421-1434. doi: 10.1007/s12325-024-03095-2. Epub 2025 Jan 23. PMID 39847314
• Results publication: Linhart A, Dostalova G, Nicholls K, West ML, Tondel C, Jovanovic A, Giraldo P, Vujkovac B, Geberhiwot T, Brill-Almon E, Alon S, Chertkoff R, Rocco R, Hughes D. Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study. Orphanet J Rare Dis. 2023 Oct 21;18(1):332. doi: 10.1186/s13023-023-02937-6. PMID 37865771

• Study Protocol (PDF, 2017-06-06)
• Statistical Analysis Plan (PDF, 2020-04-28)