dm+d
Unassigned
New Medicines
Fabry's disease in adults and children - second-line
Information
New molecular entity
Chiesi
Protalix
Development and Regulatory status
Phase III Clinical Trials
Pre-registration (Filed)
Not recommended for approval (Negative opinion )
Yes
Apr 22
The biologics license application resubmission to FDA planned for the second half of 2022 [15]
Feb 22
Protalix announces submission of MAA to EMA [12].
Nov 21
Protalix plan to submit an MAA to EMA Q1 22, and resubmit BLA to FDA H2 22 [11].
Oct 21
Protalix 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 20
FDA 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 20
Biologics License Application submitted [7].
Jan 18
Awarded fast-track status by FDA [2].
Category
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
Yes
Trial or other data
Apr 22
Company 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 22
Protalix 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 21
Protalix 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 20
Protalix 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 19
PIII study (NCT03018730) now has estimated primary completion of January 2020 [5].
May 19sequelae.mL/min/1.73m2/year on pegunigalsidase alfa which was also well tolerated with all adverse events being transient in nature without sequelae.[4]
Positive 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
Mar 19
Pivotal PIII study (NCT03018730) is ongoing and has completed recruitment. Collection of primary outcome data is expected to complete Jun 19 [3].
Dec 17
Both once and twice monthly dosing regimens are under investigation [1]
Feb 17
PIII 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 16
2 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].