Clinical Studies
Before a new drug can be approved to treat a disease, it must go through a long and rigorous testing process to establish that it is safe and effective. This usually takes several years and is done in several phases. (Visit the Genzyme corporate website for an introduction to the clinical study process.)
Before it was commercially available to people with Fabry disease, Fabrazyme® (agalsidase beta) was tested in clinical studies.
Clinical Studies of Fabrazyme
Phase 1/2 Study
The phase 1/2 clinical study of Fabrazyme involved 15 male patients with Fabry disease. In this study, Fabrazyme was tested at five different dosing regimens: 0.3, 1.0 or 3.0 milligrams (mg) per kilogram (kg) of body weight administered by IV infusion every 2 weeks or 1.0 or 3.0 mg per kg of body weight administered every 48 hours. Patients received a total of 5 infusions. This small study provided preliminary information on how Fabrazyme acts in the body, as well as information about the safety of Fabrazyme infusions.
Phase 3 Study
The phase 3 clinical study involved 58 patients (56 males and 2 females) from around the world. In this 5 month study, Fabrazyme was tested at a dose of 1.0 mg per kg of body weight administered by IV infusion every 2 weeks. Half of the patients received Fabrazyme, and half of the patients received a placebo (inactive substance). The goals of the phase 3 study were to see how well Fabrazyme worked to reduce the amount of GL-3 in certain cells of the kidney, heart, and skin.
In patients who received Fabrazyme, GL-3 was reduced to normal or near normal levels in certain types of cells in the kidney (20 of 29, or 69%), heart (21 of 29, or 72%), and skin (29 of 29, or 100%). In patients who received a placebo, GL-3 was not reduced in these cells. Treatment with Fabrazyme may improve the signs and symptoms of Fabry disease; however, the relationship of between GL-3 reduction and the improvement of specific signs and symptoms has not been established.
All patients received anti-fever medications and an antihistamine prior to their infusions. The most common side effects reported with Fabrazyme were chills, fever, and skeletal pain. Skeletal pain reported during the study was most likely due to Fabry disease and not due to the Fabrazyme infusion. When chills and fever occurred, they were managed by slowing down the infusion and by treatment with additional anti-fever medications and antihistamines.
Phase 3 Extension Study
All 58 patients from the phase 3 study chose to enroll in an extension study in which all patients received Fabrazyme at a dose of 1.0 mg per kg of body weight administered by IV infusion every 2 weeks. After 6 months in the phase 3 extension study, the amount of GL-3 in certain cells of the kidney, heart, and skin remained reduced to normal or near-normal in patients who originally received Fabrazyme and was decreased to normal or near-normal in patients who originally received placebo during the phase 3 study.
All patients received anti-fever medications and some patients received an antihistamine prior to their infusions. After 36 months of treatment in the extension study, the most common side effects reported with Fabrazyme were infusion reactions and included chills, drowsiness, feeling cold / warm, fever, nasal congestion, nausea, and headache. These side effects were managed by slowing down the infusion and by treatment with anti-fever medications, antihistamines, and oral steroids. Infusion reactions occurred in some patients after receiving anti-fever medications, antihistamines, and oral steroids. Infusion reactions declined in frequency with continued use of Fabrazyme; however, serious infusions reactions occurred after extended durations of Fabrazyme treatment. In this study, overtime, a majority of patients completed one or more full infusions in 2.0 hours or less. Individual results with Fabrazyme infusion times may vary. Some patients experienced allergic reactions to Fabrazyme, and some of these patients successfully received Fabrazyme after experiencing an allergic reaction to Fabrazyme.
|
Indications and Usage
Fabrazyme (agalsidase beta) is used to treat patients with Fabry disease. Fabrazyme lowers the amount of a substance called globotriaosylceramide (GL-3), which builds up in cells lining the blood vessels of the kidney and certain other cells.
The lowering of GL-3 suggests that Fabrazyme may improve how Fabry disease affects your body; however a relationship of lower GL-3 to specific signs and symptoms of Fabry disease has not been proven.
Important Safety Information
Life-threatening severe allergic (anaphylactic) reactions have been seen in patients during Fabrazyme infusions. Approximately 1% of patients who have received Fabrazyme either during a clinical study or after Fabrazyme was approved have experienced anaphylactic or severe allergic reactions during their infusion. These reactions have included: localized swelling of the face, mouth and throat, narrowing of breathing airways, low blood pressure, hives, difficulty swallowing, rash, trouble breathing, flushing, chest discomfort, itching and nasal congestion. People who have experienced these reactions have required treatment including heart/lung resuscitation, oxygen, fluids given through the vein, hospitalization, and have needed treatment with inhaled drugs called beta-adrenergic agonists to help open the breathing airways, antihistamines, epinephrine (also known as adrenalin), and a medication given through the vein called a corticosteroid (or steroid) which helps to decrease the body’s allergic reaction by decreasing inflammation. If you experience a severe allergic or anaphylactic reaction, your healthcare professional will immediately stop the infusion of Fabrazyme and provide you the necessary emergency medical treatment. Because of the possibility that severe allergic reactions may occur, appropriate medical support should be available during your Fabrazyme infusion.
For patients who have had reactions to their infusions, it is recommended that they be given anti-fever and antihistamine medications right before their next infusions. Infusion reactions have happened in some patients even after taking these medications and steroids by mouth before their infusions. If an infusion reaction occurs, slowing the infusion rate, stopping the infusion for a short time and/or giving more anti-fever and antihistamine medications and or steroids may improve the symptoms. If severe infusion reactions happen, your healthcare professional should consider stopping the Fabrazyme infusion right away and should provide medical care for your condition. Severe reactions are generally managed by giving antihistamine medications, corticosteroids, fluids through the vein, and/or oxygen when needed. Because severe infusions reactions may happen, medical treatment should be readily available during your Fabrazyme infusion.
Providing Fabrazyme to patients who have experienced severe or serious allergic reactions to Fabrazyme should only be done after carefully considering the risks and benefits of continuing the treatment, and only under the direct supervision of a qualified healthcare professional and with appropriate medical support readily available.
The most common side effects reported with Fabrazyme are infusion reactions, some of which were severe. When Fabrazyme was tested in clinical studies, infusion reactions occurred in approximately 50-55% of patients. Serious and/or frequently occurring side effects (occurring in 5% or more of the patients) thought to be related to Fabrazyme have included one or more of the following: chills, fever, feeling hot or cold, trouble breathing, nausea, flushing of the skin, headache, vomiting, burning and/or tingling sensation, fatigue, itching, pain in the hands and feet, high blood pressure, chest pain, throat tightness, abdominal pain, dizziness, rapid heart rate, nasal congestion, diarrhea, swelling in the legs, muscle pain, back pain, paleness of the skin, slow heart rate, hives, low blood pressure, face swelling, rash and sleepiness.
People with advanced Fabry disease may have heart problems, which may put them at a higher risk for severe complications from infusion reactions, and these patients should be watched closely during their infusion if the decision is made to give them Fabrazyme.
Other serious side effects that were seen in the clinical studies included stroke, pain, lack of muscle coordination, slow or irregular heartbeat, stopping of the heartbeat , decreased blood pumped by the heart, dizziness, hearing loss, and kidney problems resulting in too much protein leaving the body in the urine (nephrotic syndrome). These side effects also occur as part of Fabry disease.
Severe and serious infusion reactions have been reported since Fabrazyme has been approved, some of which were life threatening including anaphylactic shock (a severe allergic reaction). In addition to the above side effects, the following have been reported since Fabrazyme has been approved: joint pain, lack of strength or energy, redness of the skin, increased sweating, reactions at the place where the catheter to give the infusion is placed, increased tearing from the eyes, allergic inflammation of blood vessels, enlarged lymph nodes, decreased sensitivity to touch or pressure, decreased sensitivity of the mouth, sensations of an abnormal heartbeat, runny nose, low oxygen (in general), and low oxygen levels reaching different parts of the body.
Since Fabrazyme has been approved, there have been side effects that resulted in death that may or may not be related to the use of Fabrazyme. These included: the heart and/or lungs stop working (known as cardiorespiratory arrest, respiratory failure, and/or cardiac failure), life-threatening infection in the blood stream (known as sepsis), stroke, heart attack, kidney failure, and pneumonia. Some of these side effects were reported in Fabry disease patients with significant underlying disease.
The safety and effectiveness of Fabrazyme in patients younger than 8 years of age have not been studied.
Most patients taking Fabrazyme who develop IgG antibodies, which are commonly produced by your immune system in response to things it does not recognize as naturally being part of your body, do so within the first three months of taking the medication. In children, the development of these IgG antibodies was associated with Fabrazyme staying in the body for a longer time (prolonged half-life), which was rarely seen in adult patients.
In the clinical studies, a few patients developed IgE antibodies or a reaction to an allergy skin test specific to Fabrazyme. IgE antibodies are usually produced by the body’s immune system during an allergic reaction. Your doctor should consider testing for IgE antibodies if you experience suspected allergic reactions and consider the risks and benefits of continued treatment with Fabrazyme if you have IgE antibodies against Fabrazyme.
Fabrazyme is available by prescription only. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2.
To learn
more, please see the full Prescribing Information (PDF) or contact Genzyme at 1-800-745-4447.
|
|
 |
|
Genzyme Corporate
