FDA Grants Full Approval For SPRYCEL For The Treatment Of Adults With Chronic Myeloid Leukemia
Main Category: Lymphoma / Leukemia / MyelomaAlso Included In: Regulatory Affairs / Drug Approvals; Cancer / Oncology
Article Date: 27 May 2009 - 7:00 PDT
email to a friend
printer friendly
view / write opinions
Leukemia Clinical Trial
Experimental Transplant Available No Donor Match Required
www.immunovative.net
Bristol-Myers Squibb Company (NYSE: BMY) announced that the U.S. Food and Drug Administration (FDA) has granted full approval for SPRYCEL® (dasatinib) for the treatment of adults in all phases of chronic myeloid leukemia (CML) (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy including Gleevec®* (imatinib mesylate).
SPRYCEL, an oral tyrosine kinase inhibitor, was originally approved under the accelerated approval regulations of Subpart H for new drugs for serious or life-threatening illnesses of the Food, Drug and Cosmetic Act, based on its effectiveness on hematologic and cytogenetic response rates in CML.
The full approval was based in part on results from a Phase 3 randomized, open-label dose-optimization study that enrolled 670 chronic phase CML patients with resistance or intolerance to Gleevec. The primary endpoint of this study was major cytogenetic response (MCyR) (0-35 percent Ph+ metaphases, which combines both complete and partial responses), in Gleevec-resistant patients. The data included a minimum of two years of follow up after the start of treatment with SPRYCEL 100 mg once daily, which is the recommended starting dose of SPRYCEL for chronic phase CML patients resistant or intolerant to Gleevec. A summary of results from the 167 patients who received SPRYCEL 100 mg once daily include:
- 80 percent progression-free survival (95% CI: 73%-87%) estimated rate at two years, based on Kaplan-Meier estimates
- 91 percent overall survival (95% CI: 86%-96%) estimated rate at two years, based on Kaplan-Meier estimates
- 63 percent of patients achieved MCyR (95% CI: 56%-71%; median duration of treatment was 22 months)
- 93 percent of patients who achieved MCyR maintained that response for 18 months (95% CI: 88%-98%), based on Kaplan-Meier estimates
"SPRYCEL helps to fulfill a need for second-line treatments for CML patients with resistance or intolerance to Gleevec. The two-year follow-up data further support the use of SPRYCEL as an important treatment option for this patient population," said Dr. Hagop Kantarjian, Chairman and Professor, Leukemia Department, MD Anderson Cancer Center.
The approved label also now includes a new recommended starting dosage of SPRYCEL® (dasatinib) 140 mg once daily for accelerated, myeloid blast and lymphoid blast phase CML resistant or intolerant to prior therapy including Gleevec and Ph+ ALL resistant or intolerant to prior therapy.
Safety data in the labeling encompasses results from seven clinical trials and more than 2,100 patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The most frequently reported serious adverse reactions with SPRYCEL included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and central nervous system (CNS) hemorrhage (1%). The most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea and hemorrhage.
About SPRYCEL
On June 28, 2006, the FDA granted accelerated approval of SPRYCEL for the treatment of adults in all three phases of CML (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy including Gleevec. The FDA also granted full approval of SPRYCEL for the treatment of adults with Ph+ ALL with resistance or intolerance to prior therapy.
SPRYCEL is the first approved oral tyrosine kinase inhibitor that, at nanomolar concentrations, inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRß kinases. The active ingredient of SPRYCEL is dasatinib. Dasatinib reduces the activity of one or more proteins responsible for the uncontrolled growth of the leukemia cells of patients with CML or Ph+ ALL.
Source
Bristol-Myers Squibb
Media Contact: Scott Maier
214-648-3404
scott.maier@utsouthwestern.edu
UT Southwestern researchers show new drug
may help treat certain forms of leukemia
DALLAS – May 2, 2005 – A new experimental drug may be effective against a certain form of leukemia resistant to current treatments, research at UT Southwestern Medical Center shows.
“This novel anti-leukemia drug that we have been working on shows considerable promise for going into the clinic,” said Dr. Robert Ilaria Jr., associate professor of internal medicine and molecular biology and senior author of the study that will appear in an upcoming issue of Blood. The study is available online.
The study on the drug, called PD166326, was done in mice with a form of leukemia similar to human chronic myelogenous leukemia (CML), which is diagnosed in about 5,000 people in the United States each year. Patients with CML produce a mutated enzyme that stimulates white blood cells to overproduce, causing leukemia.
The Blood study shows that PD166326 is nearly 100 times more potent than the current drug imatinib (Gleevec) against cells expressing this enzyme, Dr. Ilaria said.
“Our study represents the first published characterization of this novel anti-leukemia drug in animals,” Dr. Ilaria said.
Gleevec is approved by the Food and Drug Administration for the treatment of patients with CML. The drug blocks signals within cancer cells and prevents a series of chemical reactions that cause the cells to grow and divide.
Although Gleevec has been highly successful against CML, it is unknown whether the drug can permanently eradicate all leukemia cells with the specific aberrant enzyme found in CML patients. About 15 percent to 20 percent of patients who take Gleevec become resistant to the drug and relapse, leaving few effective treatment options.
In the Blood study, Dr. Ilaria and his colleagues introduced the cancer-causing enzyme into mouse bone-marrow cells to generate mice with a form of leukemia similar to human CML. The disease usually develops slowly, although it can progress to an accelerated phase.
When mice received a single oral dose of PD166326, the mutated enzyme activity was rapidly inhibited, and the white blood count significantly decreased. Two-thirds of the PD166326-treated mice also had complete recovery from splenomegaly, an abnormal enlargement of the spleen, compared to none treated with Gleevec, Dr. Ilaria said.
In long-term use, PD166326 showed better anti-leukemia activity than Gleevec, and it also prolonged the survival of mice with the CML-like leukemia resistant to Gleevec treatment.
While PD166326 is not yet available for clinical trials, investigators at Memorial Sloan-Kettering Cancer Center in New York, who synthesized the drug, are working with a major pharmaceutical company that owns the patent for this class of drugs on its clinical development, Dr. Ilaria said. Its relatively long half-life in mice indicates once-daily dosing might be possible in humans.
PD166326 is in a different class of anti-leukemia drugs currently being investigated by other researchers for their effectiveness in Gleevec-resistant patients. Dr. Ilaria’s lab is continuing research in Gleevec resistance and looking at combining this new compound with other drugs.
“CML patients may soon have multiple choices with Gleevec and any one or all of the additional classes of drugs in development,” Dr. Ilaria said. “These compounds also may work on other solid tumors, so it will be very interesting to see how it all pans out.”
Nicholas C. Wolff, research associate in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research, is first author of the Blood study.
The research was supported by the National Institutes of Health; Department of Defense; National Cancer Institute; Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Cancer Foundation for Research and the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center; the Leukemia and Lymphoma Society Translational Research Program; the United Leukemia Fund; and the Westvaco Corp. and MeadWestvaco.
###
This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via e-mail,
subscribe at www.utsouthwestern.edu/receivenews
If you want to contact me please write to lauradedering@epix.net