March 12, 2020 – Results from a real-world, observational study and a clinical trial on long-term treatment with Fabrazyme® (agalsidase beta) for people living with Fabry disease are now included in FDA-approved label. Fabrazyme was granted accelerated approval by the FDA in 2003 and is the first approved treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
“Fabry disease is an X-linked genetic disease affecting approximately 10,000 women and men worldwide,” said Dr. Robert J. Desnick, lead investigator and Dean for Genetics and Genomic Medicine at the Icahn School of Medicine at Mount Sinai. “These findings are a remarkable contribution to the on-going understanding of this rare disease and the long-term impact of Fabry on renal function and clinically significant events.”
A randomized (2:1 Fabrazyme to placebo), double-blind, placebo-controlled, multinational, multicenter clinical study in 82 adult patients with Fabry disease, all naïve to enzyme replacement therapy, evaluated time to first occurrence of a clinically significant event (renal, cardiac, or cerebrovascular event, or death). Patients received either Fabrazyme or placebo for up to 35 months (median follow up 18.5 months). A total of 14 of 51 (28 percent) Fabrazyme-treated patients and 13 of 31 (42 percent) placebo-treated patients experienced a clinically significant event. The estimated hazard ratio for the risk of clinically significant events was 0.57 (95% CI: 0.27, 1.22).
A long-term observational study assessed the rate of decline in renal function (eGFR) in 122 Fabrazyme treated patients (16 years or older) matched 1:1 with a historical cohort of 122 untreated patients matched based on age, sex, classic or non-classic Fabry disease subtype, and baseline estimated glomerular filtration rate (eGFR). The median follow-up time was 3 years in the untreated group and 4.5 years in the treated group (maximum of 5 years in both groups). The estimated mean slope of eGFR was -1.5 mL/min/1.73 m2/year in the Fabrazyme-treated group and -3.2 mL/min/1.73m2/year in the untreated group with a treatment difference of 1.7 mL/min/1.73m2/year (95% CI: 0.5, 3.0).
“We express our deepest gratitude to the thousands of patients, physicians and researchers who have contributed to the understanding of Fabry disease over the past two decades,” said Alaa Hamed, M.D. MPH, MBA, Global Head of Rare Disease Medical Affairs at Sanofi. “We believe this evidence builds on the overall understanding of the efficacy and safety profile of Fabrazyme.”
Fabry disease is a rare, genetic disease that results in the progressive accumulation of the globotriaosylceramide (GL-3) lipid throughout the body. Fabrazyme works by replacing a naturally occurring enzyme (alpha-galactosidase A) to help clear GL-3 build-up in cells, including those lining the blood vessels of the kidneys, heart and skin. Fabrazyme can be used regardless of genotype, disease severity, or level of enzyme activity. The most common adverse reactions which have occurred in ≥20 percent of patients treated with Fabrazyme and >2.5 percent compared to placebo are upper respiratory tract infection; chills; fever; headache; cough; burning or prickling sensation in the hands, arms, legs or feet; fatigue; accumulation of fluids causing swelling in lower limbs; dizziness; and rash.
About Fabry Disease
Fabry disease is caused by a mutation of the GLA gene, resulting in a decreased production of the enzyme (alpha-galactosidase A or alpha-GAL A) responsible for breaking down a lipid (globotriaosylceramide or GL-3) in the body. Without this enzyme in the lysosomes, the lipid builds up throughout the body, including in blood vessels in the kidneys, skin, heart and nervous system. The progressive accumulation of GL-3 damages the cells over time and leads to symptoms that vary in severity from person to person. Common symptoms include pain, especially in the hands and feet; persistent fatigue; clusters of small, dark red skin spots (angiokeratomas); a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal whorling); hearing loss. Fabry disease can also cause damage to organs, including life-threatening conditions like kidney failure, heart disease and stroke.1
Sanofi Genzyme’s decades of nephrology experience
For nearly 40 years, Sanofi Genzyme has been a true trailblazer in providing treatments for people with rare diseases and the company continues to focus on developing potential new treatments for rare diseases where options do not currently exist. Sanofi Genzyme has researched treatments, educated physicians and supported patients living with genetic kidney diseases that impact normal renal function (nephrology), including Fabry disease, for more than two decades.
INDICATION AND USAGE
Fabrazyme® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Anaphylaxis and Hypersensitivity Reactions
In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions during Fabrazyme infusion. Life-threatening anaphylactic and severe hypersensitivity reactions have been observed in patients during Fabrazyme infusions.
- Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion.
- Interventions have included cardiopulmonary resuscitation, oxygen supplementation, IV fluids, hospitalization, and treatment with inhaled beta-adrenergic agonists, antihistamines, epinephrine, and IV corticosteroids.
- If anaphylactic or severe hypersensitivity reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Because of the potential for severe hypersensitivity reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
In clinical trials with Fabrazyme, some patients developed IgE antibodies or skin test reactivity specific to Fabrazyme.
- Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-Fabrazyme antibodies and in adult patients with high antibody titer compared to that in antibody negative adult patients.
- Physicians should consider testing for IgE antibodies in patients who experienced suspected hypersensitivity reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies. Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.
Infusion-Associated Reactions
In clinical trials with Fabrazyme, 59% of patients experienced infusion-associated reactions, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion. The incidence of infusion-associated reactions was higher in patients who were positive for anti-Fabrazyme antibodies than in patients who were negative for anti-Fabrazyme antibodies.
- In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment.
- If an infusion-associated reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.
- If severe infusion-associated reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen when clinically indicated. Because of the potential for severe infusion-associated reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions. Monitor closely patients with compromised cardiac function if Fabrazyme is administered to these patients
ADVERSE REACTIONS
- Common adverse reactions reported (≥20% and >2.5% compared to placebo) were upper respiratory tract infection (53% vs 42%), chills (49% vs 13%), pyrexia (39% vs 22%), headache (39% vs 28%), cough (33% vs 25%), paresthesia (31% vs 18%), fatigue (24% vs 17%), peripheral edema (21% vs 7%), dizziness (21% vs 8%), and rash (20% vs 10%).
Please see full Prescribing Information for Fabrazyme.
References
- Fabry Disease. U.S. National Library of Medicine. Accessed November 2020.
About Sanofi
Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.
With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.
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