The outlook is BRIGHT for Fabry disease

"We believe PRX-102 (pegunigalsidase alfa) has the potential to deliver significant advantages to Fabry disease patients, including a longer circulatory half-life and reduced immunogenicity,” says Giacomo Chiesi, head of Chiesi Global Rare Diseases".
CREDIT: Chiesi Global Rare Diseases 

CARMIEL, Israel—Chiesi Global Rare Diseases and biopharmaceutical company Protalix Bio Therapeutics Inc. recently announced positive topline results from the BRIGHT Phase 3 clinical trial evaluating pegunigalsidase alfa (PRX-102) for the potential treatment of Fabry disease.

The BRIGHT study began as a 12-month, open-label, switch-over study designed to evaluate the safety, efficacy, and pharmacokinetics of PRX-102 in up to 30 patients with Fabry disease and previously treated with a commercially available enzyme replacement therapy (ERT). PRX-102 is an ERT created from a plant-based platform used to produce the recombinant version of the α-Galactosidase-A protein.

Results of the study showed PRX-102 was well tolerated, while stable clinical presentation was maintained in treated patients. No new patients developed treatment-induced anti-drug antibodies (ADA) following the switch to PRX-102. After completion of the study, all patients chose to enroll in a long-term extension study. The companies intend to report final data in the second half of 2021.

“Fabry disease is a lysosomal storage disorder caused by mutations in the α-galactosidase-A (GLA) gene, resulting in a deficiency of the GLA enzyme, which is responsible for the breakdown of a fatty substance called globotriaosylceramide (Gb3),” explained Giacomo Chiesi, head of Chiesi Global Rare Diseases. “The mutations are inherited (from the X chromosome of a parent carrier), so multiple family members can have the disease. Early signs of the disease start in childhood and adolescence.”

 Fabry disease “can impact different people in different ways, but generally, it affects many organs including the heart, kidney, and nervous system,” Chiesi told DDN. “Because Fabry is a progressive disease, this often leads to organ damage, life-threatening complications, and a reduced life expectancy.”

This rare disorder occurs in one in every 40,000 to 60,000 people worldwide, according to Chiesi. Misdiagnosis is common, partly because of the rarity of the disease and because the multi-systemic signs and symptoms can overlap with those from a number of other diseases. The fact that the severity and age of onset of Fabry disease can vary also presents diagnostic challenges.

While there are enzyme replacement therapies commercially available to patients with Fabry disease, some patients can continue to lose kidney function despite treatment, Chiesi noted. Current ERTs also present challenges with the development of anti-drug antibodies, an inability to penetrate all tissues including a limited effect on cardiac involvement, and a short half-life that leaves many patients with debilitating symptoms between infusions.

“We believe PRX-102 (pegunigalsidase alfa) has the potential to deliver significant advantages to Fabry disease patients, including a longer circulatory half-life and reduced immunogenicity,” Chiesi remarked. “The positive results from the Phase 3 BRIGHT study we recently announced show that PRX-102 was well tolerated and stable clinical presentation was maintained in patients following the switch from currently available ERTs to PRX-102 treatment.”

The BRIGHT study results were obtained using a different administration schedule of 2mg/kg administered monthly, he said. These results are encouraging and indicate that PRX-102 may be an effective and important treatment option for Fabry patients. Many diagnosed patients remain untreated.

“For our next steps, we look forward to reporting final data from the BRIGHT study in the second half of 2021,” Chiesi stated. “We also eagerly await the PDUFA for PRX-102, which is on April 27, 2021. We filed the Biologics License Application (BLA) for PRX-102 to the FDA via the accelerated approval pathway last year and it was accepted in August 2020 and granted Priority Review designation. We are confident in the BLA submission package that includes a comprehensive set of preclinical, clinical and manufacturing data. We are working diligently and in collaboration with the agency and our partner, Protalix BioTherapeutics, to satisfy all requirements necessary for an approval and are especially grateful for the support from the FDA in this process.”

“At Chiesi, we are committed to revolutionizing the lives of people with rare diseases. For Fabry disease, our goal is to support patients whose condition cannot be adequately treated by currently approved therapies and fulfill an unmet need.”

PRX-102 is purposefully designed to be long-lasting through chemical modifications introduced to the enzyme through PEGylation, and may lead to several potential benefits for Fabry disease patients, including improved control over the course of their disease, increased bioavailability, reduced immunogenicity to therapy, reduced infusion time, lower risk of infusion reactions, reduced need for premedication before infusion, and an improved dosing schedule with an at-home dosing option, he pointed out.

“We are excited to share these topline results from the BRIGHT study, our third consecutive positive clinical trial of PRX-102, following the Phase 1/2 and the BRIDGE clinical studies,” commented Einat Brill Almon, Protalix’s senior vice president and chief development officer. “The results indicate that this investigational therapy is well tolerated and potentially an effective treatment for adult patients living with Fabry disease.”

“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 percent of the patients enrolled in the BRIGHT study have been treated with this treatment regimen for over two years. We look forward to advancing this study and further evaluating the results.”

Chiesi Global Rare Diseases https://www.chiesiglobalrarediseases.com/

Protalix Bio Therapeutics Inc. https://protalix.com/