Pegunigalsidase Alfa Demonstrates Efficacy in Phase 3 Fabry Disease Study

Einat Brill Almon, PhD

Protalix BioTherapeutics and Chiesi Global Rare Diseases announced the publication of the phase 3 BRIGHT clinical trial (NCT03180840) that evaluated the efficacy of pegunigalsidase alfa, also known as PRX-102, in adults with Fabry disease. All told, 2 mg/kg of PRX-102 administered by intravenous infusion every 4 weeks was found to be well-tolerated among treated patients, and stable clinical presentation was maintained in patients with the disease.¹

Pegunigalsidase alfa is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recumbent a-Galactosidase-A enzyme. The treatment is designed to covalently bound protein sub-units via chemical cross-linking using short PEG moieties, resulting in a molecule with unique pharmacokinetic parameters.

The 12-month open-label, switch-over BRIGHT study included 30 patients with Fabry disease previously treated with a commercially available enzyme replacement therapy (ERT) such as agalsidase alfa or agalsidase beta for at least 3 years prior and were on a stable dose administered every 2 weeks.

After receiving treatment with pegunigalsidase alfa 2 mg/kg every 4 weeks, no patients developed treatment-induced anti-drug antibodies (ADA). No Fabry clinical events were reported during the study either.

"The results indicate that this investigational therapy is well tolerated and potentially an effective treatment for adult patients living with Fabry disease," Einat Brill Almon, PhD, senior vice president and chief development officer, Protalix, said in a statement. "We are encouraged to see that all of the patients who completed this study chose to enroll in the long-term extension study. Currently, 80% of the patients enrolled in the BRIGHT study have been treated with this treatment regimen for over 2 years. We look forward to advancing this study and further evaluating the results."

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Plasma lyso-Gb3 concentrations remained stable during the study with a mean change of 3.01 nM from baseline (19.36 nM) to week 52 (22.23 nM). During the 52-week treatment period, mean absolute change of Estimated Glomerular Filtration Rate (eGFR) values remained stable, with a mean change from baseline of –1.27 mL/min/1.73 m2.

Researchers also found that patient perception of their own health remained high and stable throughout the study duration. This was indicated by a survey using the Quality of Life EQ-5D-5L questionnaire, with overall health mean scores of 78.3 (±3.1) and 82.1 (±2.9) at baseline and week 52, respectively, on a 0 to 100 scale.

Using the short-form Brief Pain Inventory (BPI) questionnaire, approximately 75% of study participants had an improvement or no change in average pain severity at week 52, as compared to baseline. These results remained stable throughout the study, and pain-related results showed no increase and/or relapse in pain.

The most common Fabry disease symptoms observed were acroparesthesia, heat tolerance, angiokeratomas, and hypohydrosis. Each patient received at least 1 dose of pegunigalsidase alfa, 29 of which completed the 12-month stud. Of these 29 patients, 28 received the intended regimen of 2 mg/kg every 4 weeks throughout the study, while 1 patient was switched to pegunigalsidase alfa 1 mg/kg every 2 weeks per protocol.

"These results demonstrate the potential of PRX-102 to be an important treatment option for the Fabry community and that the 2 mg/kg of PRX-102 every four weeks regimen may offer meaningful benefits to both patients and physicians. Treating physicians will be empowered with a potential additional treatment regimen, shown to be well tolerated, that they can offer to Fabry patients, pending approval of PRX-102,” Dror Bashan, president and chief executive officer, Protalix, said in a statement.

The treatment received fast track designation in 2018 and continued to make headlines in August 2020 when the company announced that the FDA has accepted its biologics license application (BLA).² At the time, the company announced a prescription drug user fee act (PDUFA) date for January 27, 2021, but in November, the FDA extended the action date by 3 months to April 27, 2021.³

The BLA was supported by a comprehensive set of data compiled from the company’s completed phase 1/2 clinical trial as well as the related extension study succeeding the phase 1/2 clinical trial, interim data from the phase 3 BRIDGE switch-over study, and safety data from the on-going clinical studies of pegunigalsidase alfa in patients receiving 1 mg/kg every other week.

REFERENCES

1. Protalix BioTherapeutics and Chiesi Global Rare Diseases announce positive topline results from BRIGHT phase 3 open-label, switch-over clinical trial evaluating pegunigalsidase alfa 2 mg/kg every 4 weeks for treatment of Fabry disease. News release. Protalix BioTherapeutics. February 23, 2021. Accessed March 3, 2021. https://www.prnewswire.com/il/news-releases/protalix-biotherapeutics-and-chiesi-global-rare-diseases-announce-positive-topline-results-from-bright-phase-iii-open-label-switch-over-clinical-trial-evaluating-pegunigalsidase-alfa-2-mgkg-every-four-weeks-for-treatment-of-fabr-301233318.html

2. Protalix BioTherapeutics and Chiesi Global Rare Diseases announce US food and drug administration acceptance of biologics license application (BLA) for pegunigalsidase alfa for the proposed treatment of Fabry disease and grants priority review. News release. Protalix BioTherapeutics. August 11, 2020. Accessed March 3, 2021. https://www.prnewswire.com/il/news-releases/protalix-biotherapeutics-and-chiesi-global-rare-diseases-announce-us-food-and-drug-administration-acceptance-of-biologics-license-application-bla-for-pegunigalsidase-alfa-for-the-proposed-treatment-of-fabry-disease-and-grants--301109844.html

3. Protalix BioTherapeutics and Chiesi Global Rare Diseases announce extension of PDUFA date for pegunigalsidase alfa for the proposed treatment of Fabry disease. News release. Protalix BioTherapeutics. November 27, 2021. Accessed March 3, 2021. https://www.prnewswire.com/news-releases/protalix-biotherapeutics-and-chiesi-global-rare-diseases-announce-extension-of-pdufa-date-for-pegunigalsidase-alfa-for-the-proposed-treatment-of-fabry-disease-301181112.html