RARE Daily

Protalix and Chiesi Report Final Results of Phase 3 Study of Therapy for Fabry Disease

December 30, 2020

Rare Daily Staff

Protalix BioTherapeutics and Chiesi Global Rare Diseases reported final results from the BRIDGE phase 3 study of their enzyme replacement therapy for Fabry disease that confirmed it resulted in substantial improvement in renal function in patients switched from agalsidase alfa to its experimental therapy PRX-102.

The companies said the study showed a declining trend in patients’ renal function on agalsidase alfa was attenuated and improved to be similar to normal renal function decline when switched to PRX-102.

Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal α-Galactosidase-A enzyme resulting in progressive accumulation of abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in blood vessel walls throughout a person’s body. Fabry patients inherit a deficiency of the α-Galactosidase-A enzyme, which is normally responsible for the breakdown of Gb3. The abnormal storage of Gb3 increases with time and, accordingly, Gb3 accumulates, primarily in the blood and in the blood vessel walls. The ultimate consequences of Gb3 deposition range from episodes of pain and impaired peripheral sensation to end-organ failure – particularly of the kidneys, but also of the heart and the cerebrovascular system.

Pegunigalsidase alfa (PRX-102) is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recombinant α-Galactosidase-A enzyme. Protein sub-units are covalently bound via chemical cross-linking using short PEG moieties, resulting in a molecule with unique pharmacokinetic parameters. In clinical studies, PRX-102 has been observed to have a circulatory half-life of approximately 80 hours. The Company designed PRX-102 to potentially address the continued unmet clinical need in Fabry patients.

The BRIDGE study was a phase 3, 12-month open-label, single arm switch-over study evaluating the safety and efficacy of pegunigalsidase alfa, 1 mg/kg infused every two weeks, in up to 22 Fabry patients previously treated with agalsidase alfa for at least two years and on a stable dose for at least six months. Takeda markets agalsidase alfa as Replagal.

Final results of the data generated in the study showed substantial improvement in renal function as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope) in both male and female patients who were switched from agalsidase alfa to PRX-102.

Twenty of twenty-two patients completed the 12-month treatment duration. Eighteen of the patients who completed the study opted to roll over to a long-term extension study and continue to be treated with PRX-102. Following the switch to PRX-102, there was a decrease in patients with progressing or fast progressing kidney disease, and most patients achieved a stable status post-switch.

PRX-102 was well-tolerated in the study, with all adverse events being transient in nature without sequelae. Of the 22 patients enrolled in the BRIDGE study, the majority of treatment emergent adverse events were mild or moderate in severity, with two patients (9.1 percent) withdrawing from the therapy due to hypersensitivity reaction that was resolved. The most common moderate treatment emergent adverse events were nasopharyngitis, headache and dyspnea.

An immunogenicity assessment indicated that four out of 20 patients (20 percent) developed persistent antidrug antibodies over the course of the study, of which two had neutralizing activity.

“We anticipate that the BRIDGE study results will be used to support the filing of a Marketing Authorization Application (MAA) with the European Medicines Agency, and having completed the analysis, we have taken an important step in the preparations for the application,” said Dror Bashan, Protalix’s president and CEO.

In May 2020, Protalix and Chiesi Global Rare Diseases announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for pegunigalsidase alfa for the proposed treatment of adult patients with Fabry disease via the FDA’s Accelerated Approval pathway. Subsequently, the FDA accepted the BLA and granted Priority Review designation for PRX-102 for the proposed treatment of adult patients with Fabry disease. The FDA also indicated in the BLA filing communication letter that it is not currently planning to hold an advisory committee meeting to discuss the application. The action date under the Prescription Drug User Fee Act (PDUFA) for the BLA has been updated to April 27, 2021.

Photo: Dror Bashan, Protalix’s president and CEO


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