Long-term Galafold shows clinical effectiveness in real-world study
Treatment preserved kidney function, prevented serious organ complications
Long-term use of Galafold (migalastat) preserved kidney function and prevented serious organ complications in Fabry disease patients over more than three years of treatment, according to new analyses of data from a real-world patient registry.
These patients were on average older and had a relatively severe disease burden, which demonstrates Galafold’s benefits across the disease spectrum, researchers noted.
“The data presented here, which are representative of the treatment effect of [Galafold] on Fabry disease in the real-world setting, align with previous observations from clinical trials and extends the available data supporting the real-world multisystem effectiveness of [Galafold],” they wrote.
The study, “Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry,” was published in the Journal of Inherited Metabolic Disease. It was funded by Amicus Therapeutics, which markets Galafold.
Galafold approved for Fabry disease caused by certain types of mutations
Galafold is an oral chaperone therapy approved in several countries for Fabry disease patients with certain types of disease-causing mutations in the GLA gene. Briefly, it works to help stabilize abnormal versions of the alpha-galactosidase A (alpha-Gal A) enzyme, the protein that’s deficient in Fabry disease, to make them more functional.
Long-term data from clinical trials have shown that Galafold helps stabilize kidney function, protect the heart, and prevent possibly life-threatening disease-associated complications for up to nearly nine years, according to the researchers. Data on the long-term effects of treatment with real-world use are still being collected.
The Amicus-sponsored international followME Pathfinders registry is designed to look at long-term, real-world outcomes for treated and untreated Fabry patients, 12 and older, with a particular focus on patients being treated with Galafold.
The recent analysis concerned 125 registry participants receiving Galafold who’d had at least three years of treatment (mean of 3.9 years) as of August 2022. These patients had a median age of 58, with more than 80% of participants being older than 40, and 60% were male.
At enrollment, the disease burden was relatively high. Nearly 13% of participants showed signs of substantial kidney impairment, and 62% had evidence of left ventricular hypertrophy (LVH), a type of heart disease. Sixty-one percent of participants had at least two organs affected by Fabry.
Patients older than 40 had lower average kidney function and worse cardiac function compared with younger patients.
Kidney function was monitored using the estimated glomerular filtration rate (eGFR), a measure of how well the kidneys are performing their waste-filtering activities.
Kidney function relatively stable over 4 years of treatment
Results showed kidney function remained relatively stable over four years of treatment, with eGFR declining by a mean of 0.9 milliliters per minute per 1.73 square meters (mL/min/1.73m2) per year. That falls well within the established treatment goal of seeing no more than a 3 mL/min/1.73m2 decline per year, according to the researchers.
Rates of kidney decline were similar in male and female patients and in subgroups of patients divided based on their kidney function at enrollment, including those with the most significant renal impairments.
Most participants (80%) did not have a Fabry-associated clinical event, or FACE, during follow-up. FACE refers to heart, kidney, or cerebrovascular (involving blood flow in the brain or spinal cord) complications and related deaths.
Of those who did experience a FACE, the most common was a cardiac event, occurring in 24 people (19.2%). One person (0.8%) had a kidney event, and two (1.6%) had a cerebrovascular event. One 66-year-old man died due to heart failure 2.5 years after enrolling in the registry.
A range of different Fabry-causing mutations amenable to Galafold treatment were observed in the study group. The most common was one called p.N215S, a mutation known to be associated with heart disease.
Patients with p.N215S mutation older, more often male, on treatment longer
Compared to patients without the mutation, patients who had it were older, more often male, and had been treated for longer with Galafold at study enrollment. They more often showed signs of LVH and had lower kidney function.
Rates of kidney function declines were similar in the two groups. However, those with the p.N215S variant experienced a slightly higher rate of FACEs (26.3% versus 17.2%) and all complications were cardiac-related, although the overall incidence of heart complications was similar in the two subgroups.
While the analysis did not account for all relevant data, such as co-existing conditions, medications, and Fabry disease type, the researchers believe it offers a picture of how Galafold is used to treat patients in the real world, including in older patients, those with a relatively high disease burden, and women.
Altogether, “these data from the followME Pathfinders registry reinforce the multisystem treatment benefits of [Galafold], including preserved renal function and low incidence of FACEs in an older, more geographically diverse Fabry population with significant disease,” the team concluded.
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