Agalsidase Beta

Treatment with Elfabrio (pegunigalsidase alfa), given at more spaced intervals and at a higher dose than that approved for Fabry disease, appears to be safe and effective for adults with stable disease, data from a Phase 3 clinical study suggests.Developed jointly by Chiesi Global Rare Diseases and Protalix Biotherapeutics, Elfabrio is approved in the U.S., the European Union, and the U.K for infusion into a vein at a recommended dose of 1 mg/kg every other week. The goal of the BRIGHT (NCT03180840) study was to test if Elfabrio could be taken at less frequent intervals.The study included a small number of patients, so more research is needed, but “Chiesi is committed to evaluating additional evidence to confirm the long-term results of this administration schedule,” Giacomo Chiesi, executive vice president of Chiesi Global Rare Diseases, said in a company press release.  The results of the study, “A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4  weeks in adults with Fabry disease previously treated with other enzyme replacement therapies,” were published in the Journal of Inherited Metabolic Disease.Fabry disease is caused by a deficiency in the alpha-galactosidase A (alpha-Gal A) enzyme, which results in fatty substances, such as globotriaosylceramide (Gb3), accumulating in various organs, leading to a range of symptoms and complications. Recommended Reading January 19, 2024 News by Lindsey Shapiro, PhD Elfabrio slows kidney decline in adults in BRIDGE Phase 3 trial A common treatment approach for Fabry disease is enzyme replacement therapy (ERT), where a version of the missing alpha-Gal A enzyme is supplied to help ease symptoms.Elfabrio is a type of ERT for Fabry disease that’s been modified through a process called PEGylation, which helps the enzyme become more stable in the blood and stay in the body longer. The therapy is administered every other week at a dose of 1 mg/kg.The BRIGHT study tested the safety and efficacy of Elfabrio when given every four weeks at 2mg/kg in adults with Fabry disease. The study included patients who’d been on other ERTs every two weeks for at least three years. Over the one-year study, the researchers focused on tracking any treatment-related side effects.The study included 30 patients, the majority of whom were men, with most having previously used Fabrazyme (agalsidase beta). Elfabrio stayed at effective levels in the bloodstream throughout the four-week period. Nine patients had mild to moderate side effects, but none were severe. No new immune reactions developed, which was a positive outcome.To check its effectiveness, the researchers monitored kidney health using a measure called eGFR. Kidney function stayed fairly stable throughout the study. They also tracked levels of a Fabry disease biomarker called lyso-Gb3, which stayed steady in the female participants, but slightly increased in some men with prior immune responses.The findings suggest Elfabrio every four weeks is generally safe for adults with stable Fabry disease, but before less-frequent dosing can become a treatment option, more research is needed with a larger number of patients to confirm the results.

Survey results speak to why Chiesi sees a need for Elfabrio. A Chiesi survey has found widespread unmet needs among Fabry disease patients taking drugs such as Sanofi’s Fabrazyme, pointing to how the Italian drugmaker can muscle in on the market.  Chiesi won FDA approval for the Fabry disease drug Elfabrio last year. Patients already had access to Sanofi’s old stager Fabrazyme and Amicus Therapeutics' more recently approved oral challenger Galafold. But Chiesi identified a persistent unmet need, leading it to pay Protalix BioTherapeutics $50 million upfront plus $45 million to cover development costs to secure the rights to a Fabry prospect. Seeking to understand the unmet need, Chiesi and its collaborators surveyed 280 adults in the U.S. and Canada about their experience of living with Fabry. The researchers recently published the findings in the Orphanet Journal of Rare Diseases. Most, 84%, of the respondents were taking an enzyme replacement therapy (ERT) such as Fabrazyme or Takeda’s Replagal. Eleven percent of respondents were taking chaperone therapy, namely Galafold. Most of the people had unmet needs despite being on one of the approved treatments.  The most common symptoms were low energy, tingling and pain in the hands or feet. Between 60% and 72% of respondents had those symptoms. More than half of the Fabry patients had ringing in their ears or hearing loss, general body pains or stomach pains. For 51% of respondents, the symptoms were hard to control or bothersome. Symptoms temporarily worsened between infusions in around half of respondents. However, only 48% of those patients reported the worsening to their physicians. In most cases, the doctor neither changed the patient’s treatment nor prescribed them a medicine to manage the symptoms. The survey results speak to why Chiesi sees a need for Elfabrio. Chiesi’s ERT performed similarly to Fabrazyme on the primary endpoint in a head-to-head phase 3 clinical trial. Elfabrio has a longer half-life, though, suggesting symptoms may be less likely to worsen between infusions, and its PEGylated design and other elements could improve tolerability and lower the rate of infusion-related reactions. Chiesi posted sales of 3 billion euros ($3.2 billion) in 2023, supported by 65% growth at the rare disease unit that sells Elfabrio. The statement lacks details of Elfabrio sales. Protalix generated $17.5 million from sales of Elfabrio to Chiesi last year.