FDA updates the label of Tasigna to reflect that certain patients with a type of leukemia may be eli

The U.S. Food and Drug Administration today updated the product label for the cancer drug Tasigna (nilotonib) to include information for providers about how to discontinue the drug in certain patients. Tasigna, first approved by the FDA in 2007, is indicated for the treatment of patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). With today's updated dosing recommendations, patients with early (chronic) phase CML who have been taking Tasigna for three years or more, and whose leukemia has responded to treatment according to specific criteria as detected by a test that has received FDA marketing authorization, may be eligible to stop taking Tasigna.

"Patients diagnosed with CML generally face a lifetime of treatment to keep their leukemia from growing or recurring," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Today's approval shows that some patients may be able to stop treatment with Tasigna altogether if they are showing a strong response to therapy. While we welcome this progress in patient care, it's important to note that any discontinuation of treatment still means patients must be regularly monitored for disease recurrence."

CML is a cancer of the bone marrow and causes the body to make too many white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called BCR-ABL. The National Cancer Institute at the National Institutes of Health estimates approximately 8,950 patients will be diagnosed with CML this year, and 1,080 will die of the disease.

Tasigna is a kinase inhibitor that works in CML by blocking a protein called BCR-ABL, which promotes abnormal cell growth. Today's action adds information to the product label for patients and health care providers regarding the conditions under which patients may be eligible to discontinue treatment and notes that if treatment is stopped patients must be regularly monitored for disease recurrence.

The information about discontinuing Tasigna was based on two single-arm trials of patients with Ph+ chronic phase CML. The trials measured how long patients were able to stop taking Tasigna without the leukemia returning (treatment-free remission, or TFR). In both trials, patients had to meet rigorous criteria showing how their cancer had responded to treatment before stopping Tasigna. In the first trial, among the 190 newly diagnosed patients with CML who stopped Tasigna after taking it for three or more years and meeting other specified criteria, 51.6 percent were still in the TFR phase after approximately one year (48 weeks) and 48.9 percent were still in the TFR phase after approximately two years (96 weeks). In the second trial, among the 126 patients who had stopped Tasigna after taking it for three or more years after switching from the cancer drug imatinib, 57.9 percent were still in the TFR phase after approximately one year (48 weeks) and 53.2 percent were still in the TFR phase after approximately two years (96 weeks).

An important part of both trials was regular and frequent monitoring of specific genetic (RNA) information that specifies the BCR-ABL protein level in the blood with a diagnostic test that has received FDA marketing authorization. Monitoring with a test able to detect reductions of specific RNA information with high accuracy and precision is critical to the safe discontinuation of Tasigna, as this monitoring provides the first signs of relapse.

Common side effects in patients who discontinued Tasigna include musculoskeletal symptoms such as body aches, bone pain and pain in extremities. Some patients experienced prolonged musculoskeletal symptoms.

Common side effects of taking Tasigna include nausea, rash, headache, fatigue, itching (pruritus), vomiting, diarrhea, cough, constipation, joint pain (arthralgia), upper respiratory inflammation (nasopharyngitis), fever (pyrexia), night sweats, low levels of low blood platelets (thrombocytopenia) and low levels of certain blood cells (myelosuppression or thrombocytopenia, neutropenia and anemia).

Severe side effects of taking Tasigna include myelosuppression, blockages in the heart or arteries (cardiac and arterial vascular occlusive events), inflammation of the pancreas and high levels of enzymes in the blood (pancreatitis and elevated serum lipase), severe liver damage (hepatotoxicity), abnormal levels of electrolytes in the blood, metabolic abnormalities (tumor lysis syndrome), severe bleeding (hemorrhage), drug interactions with CYP3A4 inhibitors, total surgical removal of the stomach (gastrectomy) and fluid retention. Women who are pregnant or breastfeeding should not take Tasigna because it may cause harm to a developing fetus or newborn baby.

Severe side effects typically associated with Tasigna administration occurred less frequently in patients who discontinued Tasigna. However, the long-term outcomes of patients discontinuing versus continuing treatment are unknown at this time.

The labeling for Tasigna contains a boxed warning to alert health care professionals and patients about the risk of abnormal heart rhythm (QT prolongation) and sudden death. Tasigna should not be taken by patients with low levels of potassium in the blood (hypokalemia), low levels of magnesium in the blood (hypomagnesemia), or QT prolongation. Sudden deaths have been reported in patients taking Tasigna. The boxed warning also states Tasigna should not be given with drugs known to prolong the QT interval or with strong CYP3A4 inhibitors. Patients should not eat two hours prior to or one hour after taking Tasigna.

The update to the Tasigna labeling information was granted Priority Review, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition. Tasigna also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of the Tasigna label changes to Novartis Pharmaceuticals Corporation.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.