According to Fabry Disease News, patients with Fabry disease may have better outcomes when treated with enzyme replacement therapy PRX-102 over Replagal. In a one year comparison, PRX-102 seems to be safer, more effective, and more well-tolerated, especially in slowing the progression of kidney disease. Find the full presentation from the 2020 Annual WorldSymposium.
Fabry Disease
Fabry disease is a genetic lysosomal storage disorder in which globotriaosylceramide, a type of fat, builds up in the cells. The body is unable to process this fat. Patients are usually born with Fabry disease, so the fat builds up from an early age. However, it can be adult-onset in some cases.
Patients with Fabry disease may experience recurring pain in the hands and feat, cloudy vision, gastrointestinal issues, tinnitus, stroke, heart attack, and kidney damage. Kidney and heart damage is common, particularly in adult-onset Fabry disease. There are currently no FDA-approved treatments, but aspirin, adequate hydration, a special diet, ACE inhibitors, and enzyme replacement therapy may help. Learn more about Fabry disease here.
Research Findings
Enzyme Replacement Therapies
Chapter 3 of The Nonhuman Primate in Nonclinical Drug Development and Safety Assessment defines enzyme replacement therapy as “a therapeutic approach in which the specific enzyme that is absent or inactive in infected individuals is replaced with a functional enzyme molecule.”
So PRX-102 replaces and raises absent enzymes in patients with Fabry disease. In particular, it works to replace alpha-galactosidase A, which normally helps in breaking down globotriaosylceramide. The goal of PRX-102 is to allow for treatments that are farther apart, thus reducing the burden on patients. It can achieve this through its chemical modification that makes the therapy more stable than other treatments.
The Fabry Disease Trial
The open-label Phase 3 BRIDGE trial looked to understand the efficacy and tolerability of PRX-102 as a treatment for adult patients with Fabry disease. Additionally, researchers wanted to measure the disease progression and any loss (or maintenance) of kidney function. The 22 patients who contributed were between the ages of 18 and 60. They had previously received Replagal, an enzyme replacement therapy (ERT), for at least 2 years.
To start, researchers analyzed the participants for a period of 3 months while they were still taking Replagal. Then, patients were switched to intravenous injections of 1 mg/kg of PRX-102 biweekly for a period of one year. If patients finished this first trial, they then had the option to continue in an extension study.
Patients taking Replagal still had high disease biomarkers and progressive kidney disease. However, researchers wanted to see if PRX-102 could change the state of kidney disease. They wanted to create a more stable disease state for those with progressive or fast-progressing kidney disease, or at least minimize the progression status for those in the latter category.
Ultimately, researchers achieved their goal. All of the patients who had progressive kidney disease were reduced to a stable position. 67% of patients with fast-progressing kidney disease were able to reduce their progression by at least half.
The trial shows promise for future treatment. It also highlights how PRX-102 can mitigate the effects of kidney disease and damage for patients with Fabry disease. Moving forward, the Phase 3 BALANCE trial will compare the safety, tolerability, and efficacy of PRX-102 compared to Fabrazyme in protecting renal function.
