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A wide array of symptoms that affected the kidneys and cardiovascular and nervous systems led to a diagnosis of Fabry disease for a 32-year-old woman, a study in India shows.Given that Fabry has been historically considered a male disease and that women carrying a Fabry-causing mutation may not develop the disease, the case “underscores the importance of maintaining a high index of suspicion for Fabry disease, even in female patients,” wrote the researchers, who said the case also emphasizes “the need for a comprehensive diagnostic approach to ensure timely diagnosis and appropriate management.”The case study, “Fabry Disease in a Female: A Unique Case Highlighting the Variability in Clinical Presentation,” was published in Cureus. Fabry is a rare disease caused by mutations in the GLA gene that affect the production of alpha-galactosidase A (Gal A) and results in a fatty substance called globotriaosylceramide (Gb3) accumulating inside cells. Gb3 can build up in virtually any organ and tissue, leading to a wide range of Fabry signs and symptoms, including problems with the skin, eyes, heart, nervous system, kidneys, and gastrointestinal tract.“Historically, females were considered to be asymptomatic [without symptoms] carriers of defective GLA genes who were not vulnerable to the symptoms and vital organ abnormalities,” the researchers wrote.This was because the GLA gene is located within the X chromosome and women have two X chromosomes, while men have only one. A non-mutated GLA gene in one X chromosome could potentially compensate for the other chromosome’s mutated gene in women, but men having a single mutated GLA gene would always get the disease.However, increasing evidence shows women carrying only one mutated copy of the GLA gene “can exhibit a broad spectrum of clinical presentations, ranging from the complete absence of symptoms to a full manifestation of the classic disease,” said the researchers. Womens’ symptoms may manifest differently and often emerge more subtly later in life and progress slower, which causes researchers to believe Fabry disease is underdiagnosed in women. This is a problem because early diagnosis and treatment are key to reducing organ damage and improving long-term clinical outcomes.Here, researchers in India describe the rare case of a 32-year-old woman with Fabry disease who showed a wide range of symptoms.The woman sought medical treatment at an emergency room because of progressive shortness of breath for 10 days, a fever for four days, and headache, lower limb pain, and swelling around the eye for three months. She’d previously been diagnosed with high blood pressure (hypertension) and chronic kidney disease.An examination confirmed hypertension and fever, and showed her heart rate and breathing were abnormally fast. She also reported parasthesia, or sensations of tingling, burning, prickling, itching, or numbness. Bloodwork showed the woman had lower levels of hemoglobin, the protein in red blood cells that transports oxygen throughout the body.Further analysis revealed substantial impairments in her kidney function, based on elevated protein levels in the urine and elevated levels of urea and creatine in the blood. A kidney biopsy was taken to identify the underlying cause of these issues and clinicians found increased tissue stiffness in her kidneys and larger than normal podocytes, a type of kidney cell that wraps around blood vessels to help filter waste and fluid from the blood. Kidney cells also showed zebra bodies, a hallmark of Gb3 buildup in cells.The findings, along with her symptoms, led clinicians to diagnose the woman with Fabry disease.She was prescribed hemodialysis, a kidney-replacement procedure that filters blood to remove waste and excess water from the blood, and drugs to help flush excess water and salt through her urine. The woman was also given medication for her hypertension. Her condition improved and she was discharged, but continued to have hemodialysis, and regular follow-up assessments were scheduled.“This case is a rare and unique example of Fabry disease in a female patient, with symptoms affecting multiple organ systems, including the renal, cardiovascular, and neurological systems,” the researchers wrote, adding it also “illustrates the significance of recognizing Fabry disease in female patients, highlighting the need for heightened clinical awareness.”

Co-development of innovative new drug for the treatment of Fabry disease as "the world's first once-monthly subcutaneous treatment" Improves efficacy compared to existing treatment for kidney function, vascular disease, and peripheral nerve disorders YONGIN, South Korea, Sept. 3, 2024 /PRNewswire/ -- GC Biopharma announced that its collaborative project for Fabry treatment 'LA-GLA' (GC1134A/HM15421) with Hanmi Pharmaceutical has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for a Phase 1/2 clinical trial. LA-GLA is an innovative new drug for the treatment of Fabry disease as the world's first once-monthly subcutaneous treatment, which is being co-developed by GC Biopharma and Hanmi Pharmaceutical. This clinical trial aims to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of LA-GLA in patients with Fabry disease. Fabry disease is a rare genetic disorder linked to the X chromosome and classified as a type of Lysosomal Storage Disease (LSD). It results from a deficiency in the enzyme alpha-galactosidase A, which is essential for breaking down glycolipids in lysosomes. The accumulation of glycolipids due to this deficiency leads to cellular toxicity and inflammatory responses, progressively damaging multiple organs and potentially leading to severe outcomes, including death. Currently, Fabry disease is treated with Enzyme Replacement Therapy (ERT) which involves the intravenous administration of a recombinant enzyme. However, this treatment method requires patients to visit the hospital every two weeks for an infusion, leading to inconvenience. Moreover, the current method has limitations, including the burden of prolonged intravenous therapy and insufficient efficacy in preventing the progression of kidney disease. LA-GLA is an 'innovative enzyme replacement therapy" addressing the limitations of existing treatments. It significantly improves convenience with a once-monthly subcutaneous injection regimen. In preclinical studies, LA-GLA not only improves kidney function but also demonstrated superior efficacy in managing vascular disease and peripheral nerve disorders compared to existing therapies. Based on these promising results, it was designated as an Orphan Drug (ODD) by the U.S. FDA this past May. GC Biopharma and Hanmi Pharmaceutical commented, "This collaboration integrates the latest FDA-mandated clinical protocols and leverages the specialized technical expertise of both companies, enabling a rapid transition into the clinical phase." Further added, "Based on our expertise and knowledge of developing new treatments for Lysosomal Storage Disease (LSD), we will do our utmost to create new treatment options to patients suffering from Fabry disease." About GC Biopharma Corp. GC Biopharma Corp. (formerly known as Green Cross Corporation) is a biopharmaceutical company that delivers life-saving and life-sustaining protein therapeutics and vaccines. Headquartered in Yongin, South Korea, GC Biopharma Corp. is one of the leading plasma protein and vaccine product manufacturers globally and has been dedicated to quality healthcare solutions for more than half a century. This press release may contain biopharmaceuticals in forward-looking statements, which express the current beliefs and expectations of GC Biopharma's management. Such statements do not represent any guarantee by GC Biopharma or its management of future performance and involve known and unknown risks, uncertainties and other factors. GC Biopharma undertakes no obligation to update or revise any forward-looking statement contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. GC Biopharma Corp. Contacts (Media) Sohee Kim [email protected] Yelin Jun [email protected] Rachel Kim [email protected] SOURCE GC Biopharma

Pictured: Blue sign outside FDA building/JHVEPhoto/Adobe Stock The FDA has approved Chiesi Global Rare Diseases’ and Protalix BioTherapeutics’ pegunigalsidase alfa, now to be marketed as Elfabrio, for the treatment of adult patients with Fabry disease, the pharma partners announced Wednesday. Elfabrio’s label bears a boxed warning from the FDA for hypersensitivity reactions, including anaphylaxis, and recommends that medical support measures such as cardiopulmonary resuscitation equipment should be on standby when administering the treatment. Elfabrio might also trigger infusion-associated reactions, including chills, rashes and vomiting, as well as membranoproliferative glomerulonephritis, a type of kidney injury. Fabry disease is a heritable, X-linked disease caused by a defective lysosomal α-Galactosidase-A enzyme. Under healthy conditions, this enzyme facilitates the degradation of several different molecules. In patients with Fabry disease, its dysfunctional activity leads to the accumulation of the fatty substance globotriaosylceramide (Gb3). Over time, the pathologic build-up of Gb3 gives rise to the typical symptoms of Fabry disease, including pain and impaired sensation. In its most severe forms, the condition leads to organ failure, particularly of the kidneys and heart. Elfabrio is an enzyme replacement therapy that carries the recombinant version of the α-Galactosidase-A enzyme and works by restoring the body’s ability to degrade Gb3. Road to Approval Chiesi and Protalix backed Elfabrio’s FDA bid with data from a comprehensive clinical development program that included more than 140 patients followed up for around 7.5 years. The partners first submitted a Biologics License Application (BLA) seeking accelerated approval for pegunigalsidase alfa in 2020, which the FDA accepted in August of the same year. At the time, the regulator tagged it for Priority Review. In November, however, the FDA announced it would need more time to review the data package and pushed its target action date back by three months. Chiesi and Protalix backed their initial FDA bid with data from Phase I/II clinical trials and interim clinical findings from the Phase III BRIDGE study, an open-label, single-arm, switch-over study assessing the efficacy and safety of a 1-mg/kg dose of pegunigalsidase alfa given every two weeks in 22 patients. In April 2021, the FDA rejected the companies’ BLA. Armed with stronger efficacy and safety data, the partners again sought regulatory approval in November 2022. The BLA resubmission contained the full data set from BRIDGE as well as findings from another Phase III trial dubbed BRIGHT. In March 2022, the companies released data from BRIGHT, showing that a 2-mg/kg pegunigalsidase alfa dose, given every four weeks, is safe and effective in patients who had previously been treated with an approved Fabry disease enzyme replacement therapy. The BLA resubmission also included results from a third Phase III study called BALANCE, which is the program’s biggest Fabry trial, enrolling 78 patients. In the study, pegunigalsidase alfa and Sanofi’s Fabrazyme (agalsidase beta), slowed kidney function decline at comparable levels. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.