- Innovative, once-a-day oral formulation offers life-altering treatment option to broad range of iron overload patients
- Filings based on data from largest prospective clinical trials program for iron chelation therapy
Dorval, Quebec, May 17, 2005 – Today Novartis Pharmaceuticals Canada filed an application with Health Canada for a Priority Review for Exjade™ (deferasirox), the first and only once-daily oral iron chelator for the treatment of chronic iron overload due to blood transfusions. Regulatory submissions for Exjade™ have already been filed in the United States and the European Union. Exjade™, also known as investigational agent ICL670, has been granted fast-track status in the US and Switzerland. Priority Review has been requested in the US. Furthermore, Exjade™ has received Orphan Drug status* in the US, EU and Australia.
Exjade™ is an easy to administer, novel oral iron chelator. Exjade™ comes as a dispersible tablet that is mixed in water and taken once daily. Exjade™ was developed to provide the benefits of iron chelation, which is the removal of excess iron, to a greater number of patients receiving blood transfusions, and to address the needs of hundreds of adult and pediatric patients who have been using PRDesferal® (deferoxamine), the only medication currently available in Canada to treat iron overload. Desferal®, the current standard of care in iron chelation, is effective but typically requires subcutaneous infusion lasting eight to twelve hours per day, for five to seven days a week for as long as the patient continues to receive blood transfusions. Patients have been frustrated for years by the inconvenience and pain that can result from daily insertion of the deferoxamine infusion needle. In many patients, the need for transfusion and chelation therapy may be life-long.
"Actually, a considerable number of patients are not compliant with their current chelation therapy due to its difficult administration," says Dr. Denis Soulières, MD, MSc, FRCPC, director of the hemoglobinopathy and thalassemia clinic, Notre-Dame Hospital, CHUM. "Retrospective studies have shown a direct correlation between overall survival and the patient's compliance to Desferal®. It is tragic when one sees a young adult die from cardiac complications of iron overload because they have not been able to cope with the daily subcutaneous infusions. Because of its ease of use, which is likely to impact favourably on the adherence to treatment, its overall favourable efficacy and safety profile combined with the fact that it also represents a suitable alternative for Desferal® failures, Exjade has the potential to significantly improve the care of patients with transfusional iron overload."
"Desferal® infusion therapy is difficult for children, who dislike needles and fear the pain. But it is extremely burdensome for older teens and young adults, who often will not comply with therapy, even though they see first-hand the risks of iron overload including deformities, organ failure and premature death," said Durhane Wong-Rieger, PhD, president and chief executive officer, Anemia Institute for Research and Education in Canada. "Organ damage and the premature death of young adults with thalassemia are not uncommon in Canada. They can often be related to iron overload treatment failure, more specifically because of a lack of response to or an inability to comply with Desferal®. Patients and caregivers are very hopeful for a once-daily oral chelator that will enable them to continue to treat iron overload."
Iron overload causes cumulative life-threatening toxicity that results from lifesaving blood transfusions required to treat certain types of anemias and other disorders, including thalassemia, sickle cell disease, other rare anemias, and myelodysplastic syndromes. If left undiagnosed or untreated, iron overload can damage the liver, heart and endocrine glands.
Filing data
The Exjade™ global clinical trials program enrolled more than 1,000 patients, and is the largest-ever prospectively implemented for an investigational iron chelator. The filings are based on the results of pivotal clinical trials, including a Phase III head-to-head trial vs. deferoxamine, which showed that at doses of 20 mg and 30 mg /kg Exjade™ significantly reduced liver iron concentration (LIC) in adult and pediatric patients receiving blood transfusions. Findings from the clinical trial program were presented in December 2004 at the annual meeting of the American Society of Hematology. The studies demonstrated that Exjade™ led to the maintenance or reduction of absolute LIC in regularly transfused patients with different underlying diseases. Additional data on Exjade™ will be presented at four important medical meetings: the annual meeting of the American Society of Pediatric Hematology/Oncology in Washington, D.C. (May 14-16, 2005); the 8th International Symposium on Myelodysplastic Syndromes in Nagasaki, Japan (May 12-15, 2005); the First Congress of the International BioIron Society in Prague, Czech Republic (May 22-27, 2005); and the 10th Congress of the European Hematology Association in Stockholm, Sweden (June 2-5, 2005).
In the clinical studies in both adults and children as young as two years of age, Exjade™ was generally well tolerated, with the most frequently reported adverse events being nausea, vomiting, diarrhea, abdominal pain, skin rash, a mild to moderate increase in liver enzymes and mild stable increases in serum creatinine, usually within the normal range.
*Orphan drug designation and fast-track status
In the EU, the filing for Exjade™ was submitted to the European Medicines Agency under the centralized procedure. Exjade™ was granted Orphan Drug status in both the US and EU in 2002. The intent of the Orphan Drug designation is to stimulate the research, development, and approval of products that treat rare diseases. In the EU, the term “Orphan Drug” refers to a product that treats a serious or life-threatening disease that affects fewer than five people per 10,000 population. In the US, the term “Orphan Drug” refers to a product that treats a disease that affects fewer than 200,000 people in the country. Exjade™ also was granted fast-track status in the US and Switzerland. In Canada, an Orphan Drug policy does not exist. However, a Priority Review status has been requested. A Priority Review designation is generally reserved for drugs intended for the treatment of a serious or life-threatening condition that demonstrate the potential to address unmet medical needs for that condition.
Forward looking statement
The foregoing release contains forward-looking statements that can be identified by terminology such as “life-altering,” “innovative,” “easy,” “significantly,” “fast-track designation pending,” or similar expressions, or by express or implied discussions regarding potential additional marketing approvals or future sales of Exjade™. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Exjade™ to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Exjade™ will receive any additional marketing approvals in any other countries, or that it will reach any particular sales levels. In particular, management's expectations regarding commercialization of Exjade™ could be affected by, among other things, additional analysis of Exjade™ clinical data, new clinical data, unexpected clinical trial results, unexpected regulatory actions or delays or government regulation generally, the company's ability to obtain or maintain patent or other proprietary intellectual property protection, competition in general, increased government, industry, and general public pricing pressures, and other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. The purpose of this media document is for information only, and is not meant to promote or encourage a use of this medication outside the approved Product Monograph in Canada. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
