FDA grants priority review for Exjade(R) for the treatment of chronic iron overload due to blood transfusions

Main Category: Blood / Hematology
Article Date: 25 Jun 2005 - 15:00 PDT

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Novartis announced today that its New Drug Application for Exjade(R) (deferasirox) has been granted priority review by the U.S. Food and Drug Administration (FDA) as a once-daily oral iron chelator for the treatment of chronic iron overload due to blood transfusions.

The FDA grants priority review to products that could potentially offer a significant improvement compared to marketed products in the treatment, diagnosis or prevention of a disease. A novel, easy to administer oral iron chelator, Exjade is taken once daily, after dispersing tablets in a glass of water or orange juice. The current standard of care in iron chelation, deferoxamine 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. In many patients, the need for transfusion and chelation therapy may be life-long.

"The priority review by the FDA reflects the potential of Exjade to fulfill a significant unmet medical need for patients with chronic iron overload," said Diane Young, MD, vice president, global head, Clinical Development, Novartis Oncology. "We hope that once Exjade becomes available as a treatment option, it will not only improve the quality of life of those patients who for years have endured the discomfort of deferoxamine, but will also provide a new and acceptable treatment option for those who have been risking their lives by avoiding chelation therapy altogether because of the burdensome nature of the current standard of care."

A priority review establishes an action date no later than six months after the submission date, which for Exjade was in May 2005. At that time, Novartis also submitted registration applications for Exjade in the European Union, Switzerland and Australia. Exjade, also known as investigational agent ICL670, has also been granted priority review in Australia and fast track status in Switzerland. Further, Exjade has received Orphan Drug status in the U.S., EU and Australia.

Iron overload is a potentially life-threatening condition that results from frequent 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 lead to damage to the liver, heart and endocrine glands, and can be fatal. Transfused patients are often treated for iron overload with a type of drug therapy called iron chelation, which removes excess iron from the body.

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 Exjade significantly reduced liver iron concentration (LIC), an accepted indicator for body iron content, at doses of 20 and 30mg/kg/day in adult and pediatric patients receiving blood transfusions. The studies demonstrated that Exjade led to the maintenance or reduction of absolute LIC in regularly transfused patients with different underlying diseases.

The primary endpoint of the trial was the achievement of a specified reduction in LIC after one year of therapy. Those with lower initial LIC values on the deferoxamine arm were permitted to remain on their pre-study doses and were compared to patients receiving the lower doses of 5 or 10 mg/kg/day of ICL670. Therefore, many of these individuals received significantly higher doses of deferoxamine relative to ICL670. At 20 and 30 mg/kg/day ICL670 demonstrated non-inferiority when compared to deferoxamine. However, at doses of 5 and 10 mg/kg/day Exjade did not achieve non-inferiority. Thus, there is a clear dose response relationship for Exjade, demonstrating that 20 and 30 mg/kg/day are the clinically relevant doses.

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 and mild stable increases in serum creatinine, usually within the normal range.

Additional Information

To learn more about Exjade clinical trials, health care providers can call either 0800 328 9875 or +44 (0) 1506 814895.

The foregoing release contains forward-looking statements that can be identified by terminology such as "that represent," "potential," "becomes available," "if approved," "would be," "will improve," 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 U.S. 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. 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.

For prescribing information on deferoxamine please contact your local Novartis affiliate.

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

Contacts
Kim Fox
Novartis Oncology
Tel +1 862 778 7692
kim.fox@novartis.com
John Gilardi
Novartis Global Media Relations
Tel +41 61 324 3018
Mobile +41 79 596 1408
john.gilardi@novartis.com

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