New Medicines

Fabry's disease in adults and children - second-line


New molecular entity

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Not recommended for approval (Negative opinion )
Apr 22The biologics license application resubmission to FDA planned for the second half of 2022 [15]
Feb 22Protalix announces submission of MAA to EMA [12].
Nov 21Protalix plan to submit an MAA to EMA Q1 22, and resubmit BLA to FDA H2 22 [11].
Oct 21Protalix is considering a path to resubmission to FDA (traditional path vs. accelerated approval) following a complete response letter (CRL) in April 2021. Issues addressed in the CRL were inability to visit plan and the fact the comparator in clinical trials has not yet been fully approved. Protalix still plans to submit a marketing submission to EU in Q1 2022 [9].
Nov 20FDA PDUFA action date now 27 April 2021 [8]. In its Q3 2020 results summary, the company referred to potential Covid-related difficulties in FDA manufacturing plant inspection.
May 20Biologics License Application submitted [7].
Jan 18Awarded fast-track status by FDA [2].


Alpha-galactosidase replacement
Fabry disease affects approximately 5,000 to 10,000 people worldwide, but may be under diagnosed
Fabry's disease in adults and children - second-line
Intravenous infusion

Further information


Trial or other data

Apr 22Company announces positive results of PIII BALANCE trial (NCT02795676). Pegunigalsidase alfa met the primary endpoint on kidney function in active control, non-inferiority study vs. agalsidase beta. A favourable tolerability and immunogenicity profile was shown [15]
Mar 22Protalix announces final results from PIII BRIGHT (NCT03180840) clinical trial. The results indicate that treatment with 2 mg/kg of PRX-102 administered by intravenous (IV) infusion every four weeks was well tolerated, and Fabry disease assessed by estimated glomerular filtration rate (eGFR) slope and plasma lyso-Gb3 concentration was stable [14]
Oct 21Protalix announce final dosing of last patient in PIII BALANCE trial (n=78); 67 patients have enrolled in a long-term extension study, and two more are in the enrolment process [10].
May 20Protalix BioTherapeutics announce positive topline results from PIII BRIDGE trial (n=22). Study found an improvement in renal function as measured by the mean annualised eGFR slope , from 5.90 mL/min/1.73m2/year while on agalsidase alfa to -1.19 mL/min/1.73m2/year on pegunigalsidase alfa in all patients [6].
Sep 19PIII study (NCT03018730) now has estimated primary completion of January 2020 [5].
May 19Positive 12-Month interim data from PIII BRIDGE study (NCT03018730) which is evaluating the safety and efficacy of pegunigalsidase alfa 1 mg/kg infused every 2 weeks in up to 22 Fabry pts switched from agalsidase alfa (Replagal®). All progressing pts and 66.7% in the fast progressing group achieved proposed therapeutic goals after switching. The mean annualised eGFR slope improved from -5.10 mL/min/1.73m2/year while on agalsidase alfa to -0.23 Pegunigalsidase alfa was found to be well tolerated in the study, with all adverse events being transient in nature without sequelae.mL/min/1.73m2/year on pegunigalsidase alfa which was also well tolerated with all adverse events being transient in nature without sequelae.[4]
Mar 19Pivotal PIII study (NCT03018730) is ongoing and has completed recruitment. Collection of primary outcome data is expected to complete Jun 19 [3].
Dec 17Both once and twice monthly dosing regimens are under investigation [1]
Feb 17PIII internatioanl study to evaluate 1 mg/kg every two weeks in patients currently treated with agalsidase alfa (NCT03018730). The open-label, single arm study will enrol approximately 22 patients. The switch-over study is expected to run for 12 months and will provide supportive data for regulatory filings in the US and EU [1]
Jun 162 year PIII international (including UK) BALANCE trial started in patients with impaired renal function (NCT02795676). Patients previously treated with agalsidase beta for one year, and with a stable dose for at least six months randomized to continue treatment with 1 mg/kg with either Fabrazyme or peguniglasidase-alfa. The primary efficacy parameter, agreed with the FDA and the EMA, is the comparison of the mean annualized change in estimated glomerular filtration rate (eGFR) between treatment groups. The company expects an interim analysis, at 12 months, for non-inferiority will support a potential regulatory filing with the EMA [1].

Evidence based evaluations