Pegunigalsidase Alfa for Fabry Disease

(Bright51 Trial)

Recruiting at 16 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chiesi Farmaceutici S.p.A.

Disqualifiers: Medical, emotional, behavioral, psychological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 364 weeks

29 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug pegunigalsidase alfa for treating Fabry disease?

Research shows that pegunigalsidase alfa, a new enzyme replacement therapy, helps maintain kidney function and reduces harmful substances in the body for people with Fabry disease. It also has a longer-lasting effect in the bloodstream and causes fewer immune reactions compared to similar treatments. ^{1 2 3 4 5}

Is pegunigalsidase alfa safe for humans?

Pegunigalsidase alfa has been studied for safety in people with Fabry disease, and most side effects were mild or moderate. Some patients developed antibodies against the drug, but these decreased over time, and only one person left the study due to a serious side effect. ^{1 2 3 4 5}

How is the drug pegunigalsidase alfa different from other treatments for Fabry disease?

Pegunigalsidase alfa is unique because it is a PEGylated enzyme replacement therapy, which means it has a special coating that helps it stay in the body longer and reduces the chance of the immune system reacting against it. This can lead to better treatment outcomes and fewer side effects compared to other enzyme replacement therapies for Fabry disease. ^{1 2 3 4 5}

What is the purpose of this trial?

The objective of CLI-06657AA1-03 (formerly PB-102-F51) is to evaluate the long-term safety, tolerability, and efficacy of 2 mg/kg pegunigalsidase alfa administered intravenously every four weeks in adult Fabry patients who have successfully completed PB-102-F50.

Eligibility Criteria

This trial is for adult Fabry disease patients who completed the PB-102-F50 study. Participants must agree to use effective contraception if they or their partners can have children, and sign an informed consent. Those with conditions that could affect study compliance are excluded.

Inclusion Criteria

Completion of study PB-102-F50

The patient signs informed consent

I agree to use effective birth control during and for 2 weeks after the treatment.

Exclusion Criteria

Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator, would interfere with patient compliance with the requirements of the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 mg/kg pegunigalsidase alfa administered intravenously every 4 weeks

364 weeks

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving treatment until pegunigalsidase alfa is commercially available or at the discretion of the Sponsor

Long-term

Treatment Details

Interventions

• pegunigalsidase alfa

Trial Overview The trial tests the long-term safety and effectiveness of a drug called pegunigalsidase alfa, given intravenously at a dose of 2 mg/kg every four weeks to adults with Fabry disease who previously finished another related trial.

Participant Groups

Group I: Experimental open label Experimental Treatment 1 Intervention

Pegunigalsidase alfa

Who Is Running the Clinical Trial?

Chiesi Farmaceutici S.p.A.

Lead Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

Protalix

Lead Sponsor

Trials

19

Recruited

490+

Findings from Research

In a long-term study of 15 adults with Fabry disease, pegunigalsidase alfa, a new enzyme replacement therapy, demonstrated favorable safety with most side effects being mild to moderate, and no severe infusion reactions reported.

Patients showed significant reductions in plasma lyso-Gb3 levels over 60 months, indicating effective treatment, and maintained stable kidney and cardiac function, suggesting long-term benefits of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. Hughes, D., Gonzalez, D., Maegawa, G., et al.[2023]

Pegunigalsidase alfa, an enzyme replacement therapy for Fabry disease, demonstrated a significantly extended plasma half-life of 53 to 121 hours, which may enhance its efficacy and reduce immunogenicity compared to existing treatments.

In a study involving 16 symptomatic adults over one year, treatment led to an 84% reduction in kidney globotriaosylceramide (Gb3) inclusions, with most adverse events being mild or moderate, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. Schiffmann, R., Goker-Alpan, O., Holida, M., et al.[2022]

In a phase 3 study involving 20 adults with Fabry disease, pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events being mild or moderate, indicating a favorable safety profile.

After switching to pegunigalsidase alfa, the decline in kidney function (measured by eGFR) significantly slowed, with a mean eGFR slope of -1.19 mL/min/1.73 m2/year compared to -5.90 mL/min/1.73 m2/year before the switch, suggesting improved efficacy in preserving kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Linhart, A., Dostálová, G., Nicholls, K., et al.[2023]

In a study involving 77 adults with Fabry disease, pegunigalsidase alfa was found to be non-inferior to agalsidase beta in terms of kidney function, as measured by the annualized eGFR slope over 2 years.

Pegunigalsidase alfa demonstrated a better safety profile, with significantly lower rates of treatment-related adverse events and infusion-related reactions compared to agalsidase beta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study. Wallace, EL., Goker-Alpan, O., Wilcox, WR., et al.[2023]

In a study of 49 patients with Fabry disease, the novel PEGylated enzyme pegunigalsidase-alfa (PRX-102) showed significantly lower affinity for anti-drug antibodies (ADAs) compared to traditional treatments agalsidase-alfa and -beta, suggesting it may be less affected by these antibodies.

The research indicates that patients with pre-existing ADAs may experience a 30% reduction in inhibitory effects when switching to PRX-102, potentially making it a more effective treatment option for those affected by Fabry disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa. Lenders, M., Pollmann, S., Terlinden, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa. [2022]