CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Genzyme, a Sanofi company, announced today that the Ministry of Health, Labor and Welfare (MHLW) has granted marketing approval for Cerdelga® (INN: eliglustat), the only oral therapy for the treatment of adults with Gaucher disease type 1 in Japan. Cerdelga was approved by the U.S. Food and Drug Administration in August 2014, the European Commission in January 2015, and the Australian Therapeutics Goods Administration in February 2015.
The MHLW approval was based on data from the Cerdelga clinical development program, the largest clinical research program ever conducted in Gaucher disease type 1, with approximately 400 patients treated in 29 countries. The development program included three Phase 3 clinical trials. In the Phase 3 treatment-naïve, placebo-controlled trial, ENGAGE, improvements were seen across the following endpoints after 9 months on Cerdelga: spleen size, platelet levels, hemoglobin levels, and liver volume. The second Phase 3 trial, ENCORE, was designed to assess disease stability in patients previously treated with enzyme replacement therapy. That trial met the pre-specified criteria for non-inferiority to an enzyme replacement therapy (imiglucerase), which was a composite endpoint of the following parameters: spleen volume, hemoglobin levels, platelet counts, and liver volume.
The third Phase 3 trial, EDGE, included 10 Japanese patients, and was designed to evaluate different dosing frequencies of Cerdelga (in patients previously treated with enzyme replacement therapy or treatment naïve Gaucher disease patients). The EDGE trial included an interim analysis of efficacy and safety in Japanese patients. Patients in all three Phase 3 studies continue to receive Cerdelga in the extension periods, and the majority of patients are in their 4th or 5th year of treatment.
“The clinical development program for Cerdelga represents a global effort across the entire Gaucher community, and we are grateful for Japan’s efforts to provide access to Cerdelga to patients in their country,” said Genzyme’s Acting Head of Rare Diseases, Richard Peters, MD, Ph.D. “The program demonstrates Genzyme’s long-term commitment to this disease community, and we recognize the collaborative efforts of the physician and patient communities as the drivers that have made this progress possible.”
About Gaucher Disease
Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, acid β-glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease, type 1, generally does not affect the brain.
Cerdelga® (eliglustat), a novel glucosylceramide analog given orally, was designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease. The concept was initially proposed by the late Norman Radin, PhD, from the University of Michigan. In pre-clinical studies, the precursor molecule, developed with James A. Shayman, MD, also from the University of Michigan, showed specificity for glucosylceramide synthase. Following Genzyme’s extensive compound optimization, pre-clinical and early clinical development program, Cerdelga was studied in the largest Phase 3 clinical program ever conducted in Gaucher disease, with approximately 400 patients treated in 30 countries.
IMPORTANT SAFETY INFORMATION (for US Healthcare Professionals)
Indications and Usage
CERDELGA® (eliglustat) capsules are indicated for the long-term treatment of adults with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect. A specific dose cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).
Important Safety Information
CERDELGA is contraindicated in the following patients due to the risk of significantly increased CERDELGA plasma concentrations which may result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias: EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor and IMs or PMs taking a strong CYP3A inhibitor.
Drugs that inhibit CYP2D6 and CYP3A may significantly increase the exposure to CERDELGA; Cerdelga dose adjustment may be needed, depending on metabolizer status. See section 7 of the full Prescribing Information for more details and other potentially significant drug interactions.
Because CERDELGA is predicted to cause increases in ECG intervals at substantially elevated plasma concentrations, use is not recommended in patients with pre-existing cardiac disease, long QT syndrome, or in combination with Class IA and Class III antiarrhythmic medications.
The most common adverse reactions (≥10%) for CERDELGA are: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.
Only administer CERDELGA during pregnancy if the potential benefit justifies the potential risk; based on animal data, CERDELGA may cause fetal harm. Discontinue drug or nursing based on importance of drug to mother. CERDELGA is not recommended in patients with moderate to severe renal impairment or in patients with hepatic impairment.
To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at (1-800-745-4447) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including patient Medication Guide, for additional important safety information.
For full prescribing information and more information about Cerdelga for U.S. patients, please visit: http://www.cerdelga.com/pdf/cerdelga_prescribing_information.pdf.
Cerezyme Important Safety Information
Approximately 15% of patients have developed IgG antibodies to Cerezyme during the first year of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity, and these patients have a higher risk of hypersensitivity. It is suggested that patients be monitored periodically for IgG antibody formation during the first year of treatment.
Hypersensitivity has also been observed in patients without detectable IgG antibodies. Symptoms suggestive of hypersensitivity have been noted in approximately 6.6% of all patients, and anaphylactoid reactions in less than 1%. Treatment with Cerezyme should be approached with caution in patients who have exhibited hypersensitivity symptoms such as pruritus, flushing, urticarial, angioedema, chest discomfort, dyspnea, coughing, cyanosis, and hypotension. Pre-treatment with antihistamines and/or corticosteroids and a reduced rate of infusion may allow continued treatment in most patients.
In less than 1% of patients, pulmonary hypertension and pneumonia have been observed during treatment with Cerezyme. These are known complications of Gaucher disease regardless of treatment. Patients with respiratory symptoms in the absence of fever should be evaluated for the presence of pulmonary hypertension.
Approximately 13.8% of patients have experienced adverse events related to treatment with Cerezyme. Some of these are injection site reactions such as discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of venipuncture. Additional adverse reactions that have been reported include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Transient peripheral edema has also been reported for this therapeutic class of drug.
About Genzyme, a Sanofi Company
Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years. We accomplish our goals through world-class research and with the compassion and commitment of our employees. With a focus on rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the patients and families we serve. That goal guides and inspires us every day. Genzyme’s portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking and life-saving advances in medicine. As a Sanofi company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more at www.genzyme.com.
Genzyme®, Cerezyme®, and Cerdelga® are registered trademarks of Genzyme Corporation. All rights reserved.
Sanofi, a global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and Genzyme.
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