FDA Approves U.S. Product Labeling Update for Sprycel (dasatinib) to Include Three-Year First-Line and Five-Year Second-Line Efficacy and Safety Data in Chronic Myeloid Leukemia in Chronic Phase

Data added to Sprycel U.S. labeling are among the longest follow-up data of current CML treatment options

PRINCETON, N.J., June 20, 2013--(BUSINESS WIRE)--Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved an update to the Sprycel (dasatinib) product labeling. The labeling now includes three-year efficacy and safety data in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) and five-year data in CP Ph+ CML patients who are resistant or intolerant to Gleevec1 (imatinib mesylate).

Sprycel is a kinase inhibitor indicated for the treatment of adults with newly diagnosed CP Ph+ CML. The effectiveness of Sprycel is based on cytogenetic response and major molecular response rates. The trial is ongoing and further data will be required to determine long-term outcome. Sprycel is also indicated for Ph+ CML in all phases (chronic, accelerated, or myeloid or lymphoid blast) with resistance or intolerance to prior therapy including imatinib and Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy.

“These longer-term data add to the growing body of research around the safety and efficacy of Sprycel in first-line CP Ph+ CML patients and those who are resistant or intolerant to imatinib,” said Neil Shah, MD, PhD, Associate Professor, Division of Hematology/Oncology, University of California, San Francisco. “CML requires ongoing treatment and assessment of treatment milestones in order to manage the disease properly. Given the chronic nature of CML, these long-term data are particularly important for patient care.”

“Bristol-Myers Squibb remains committed to helping patients with newly diagnosed and imatinib-resistant or intolerant CP Ph+ CML through treatment with Sprycel, a convenient once-daily treatment option,” said Laura Bessen, MD, vice president and head of U.S. Medical, Bristol-Myers Squibb. “The longer-term safety and efficacy data that have been added to the Sprycel (dasatinib) U.S. labeling underscore this longstanding commitment. Since the initial FDA approval in 2006, more than 175,000 Sprycel prescriptions have been written in the U.S.”

“We are fortunate to be living at a time when, for many patients, CML can often be managed as a chronic disease, thanks to treatments like Sprycel,” said Greg Stephens, executive director, National CML Society. “As patients continue to benefit from these treatments, understanding their safety and effectiveness over time becomes increasingly important and may help inform the decisions of healthcare providers as to which therapy they choose.”

Sprycel Demonstrated Higher Response than Imatinib in Newly-diagnosed Patients

Information added to the Sprycel label in the first-line CP Ph+ CML setting is based on three-year data from DASISION (Dasatinib versus Imatinib Study in Treatment-Naïve CML Patients), an open-label, randomized, Phase 3 international trial. In the study, Sprycel demonstrated superior efficacy as defined by higher molecular (major molecular response2 or MMR) and confirmed cytogenetic response rates (CCyR3) by 12 months, compared to imatinib.

In DASISION, 77% [95% CI, 71% - 82%] of patients treated with Sprycel (n=259) vs. 66% [95%, CI, 60% - 72%] of patients treated with imatinib (n=260) achieved the primary endpoint of confirmed CCyR (defined as two consecutive assessments of CCyR at least 28 days apart) by 12 months (p=0.007). After 36 months follow-up, median time to confirmed CCyR was 3.1 months in 214 Sprycel responders and 5.8 months in 201 imatinib responders. In the long-term (by 3 years), confirmed CCyR rates continued to increase (83% Sprycel vs. 77% imatinib).4

Sprycel patients were more likely than imatinib patients to achieve MMR2, a measure of deeper treatment response, by year one (52% [95% CI, 46% - 58%] vs. 34% [95% CI, 28% - 40%], respectively; p<0.0001). In the long term (by year 3), MMR at any time was higher for Sprycel than imatinib (69% [95% CI, 63% - 75%] vs. 56% [95% CI, 50% - 62%], respectively).4 The study also showed higher MMR rates at any time with Sprycel, across all Hasford5 risk groups vs. imatinib (low risk: 81% vs. 64%; medium risk: 64% vs. 56%; and high risk: 61% vs. 42%). In patients treated with Sprycel (dasatinib) the vast majority did not transform to accelerated or blast phase CML by three years (3% with Sprycel and 5% with imatinib).

The most frequently reported serious adverse reactions in patients with newly diagnosed CP Ph+ CML included pleural effusion (4%), hemorrhage (2%), congestive heart failure (1%), pulmonary hypertension (1%), and pyrexia (1%). The most frequently reported adverse reactions reported in ≥10% of patients with newly diagnosed CP Ph+ CML included myelosuppression, fluid retention events (pleural effusion and superficial localized edema), diarrhea, headache, musculoskeletal pain, rash, and nausea. The safety and efficacy evaluation in this trial is ongoing.

About the DASISION Study (CA180-056)

DASISION is an open-label, randomized, Phase 3 international trial of Sprycel 100 mg taken once-daily vs. imatinib 400 mg taken once-daily, in the treatment of newly-diagnosed CP Ph+ CML. The study enrolled 519 patients; 259 patients were randomized to receive Sprycel and 260 patients were randomized to receive imatinib. The primary study endpoint was confirmed CCyR3 by 12 months. Select secondary endpoints were MMR2 at any time, time to MMR, and time to confirmed CCyR. With a minimum of three years follow-up, 71% of Sprycel patients and 69% of imatinib patients were still on study.

Phase 3 Study Is First to Demonstrate Five-Year Data in Second-Line Setting

Information added to the Sprycel labeling for CP Ph+ CML patients with resistance or intolerance to prior imatinib therapy includes data up to six years after the last patient was enrolled in Study CA180-034, a Phase 3 open-label, dose-optimization trial. At five years, 64% of patients were known to be alive with an additional 14% having unknown survival data (the remaining 22% of patients were known to have died prior to five years). While on treatment, less than 5% of Sprycel patients transformed to accelerated or blast phase CML by five years. The primary endpoint was major cytogenetic response (MCyR) in imatinib-resistant patients; 63% of imatinib-resistant or -intolerant patients taking Sprycel (dasatinib) 100 mg once-daily achieved MCyR at two years [95% CI: 56% - 71%].

The most frequently reported serious adverse reactions 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 CNS hemorrhage (1%). The most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events (pleural effusion and superficial localized edema), headache, diarrhea, fatigue, dyspnea, and musculoskeletal pain. The efficacy evaluation, including transformation rates, is ongoing.

About Dose Optimization Study (CA 180-034)

The dose optimization study (CA180-034) is an open-label, randomized study designed to assess the efficacy and safety of Sprycel in CP Ph+ CML patients with resistance (n=497) or intolerance (n=173) to imatinib. The trial enrolled 670 CML patients who were randomized to one of four treatment arms: 100 mg once-daily (n=167), 50 mg twice-daily (n=168), 140 mg once-daily (n=167), and 70 mg twice-daily (n=168). Efficacy was achieved across all Sprycel treatment groups with the once-daily schedule demonstrating comparable efficacy (non-inferiority) to the twice-daily schedule on the primary efficacy endpoint (difference in MCyR 1.9%; 95% CI [-6.8 – 10.6%]). In this population, the median time from onset of CML to randomization in patients on the 100 mg once-daily arm was 55 months and 46% of these patients had more than three years of prior imatinib treatment. The study supports the recommended starting dose, 100 mg once-daily, for CP Ph+ CML patients resistant or intolerant to imatinib. The safety data through year five were consistent with the previously reported safety profile of Sprycel 100 mg once-daily in patients resistant or intolerant to imatinib.

About Sprycel Patient Support

Bristol-Myers Squibb is committed to patient support, which includes co-pay assistance for eligible Sprycel patients. Through the Sprycel One Card Program, commercially insured Sprycel patients may be able to pay no more than $25 per month, with a maximum annual benefit of $25,000. Eligibility requirements and terms and conditions apply.

About Chronic Myeloid Leukemia

CML is a type of leukemia in which the body produces an uncontrolled number of abnormal white blood cells. According to the most recent statistics, about 28,900 people are living with the disease in the United States. It is estimated that 5,920 new cases will be diagnosed in 2013. CML occurs when pieces of two different chromosomes (chromosomes 9, 22) break off and attach to each other. The newly formed chromosome is called the Philadelphia chromosome, which contains an abnormal gene called BCR-ABL gene. This gene produces the BCR-ABL protein that signals cells to make too many white blood cells. There is no known cause for the genetic change that results in CML.

About Sprycel (dasatinib)

Sprycel was first approved for the treatment of adults with CP Ph+ CML who are resistant or intolerant to prior therapy including imatinib in 2006 by the FDA. At that time, Sprycel was also approved for adults with Ph+ ALL who are resistant or intolerant to prior therapy. It is the first and only kinase inhibitor with survival data in its label for CP Ph+ CML patients who are resistant or intolerant to imatinib. Sprycel is now approved and marketed worldwide for these indications in more than 60 countries including the European Union (EU), Japan and Canada.

Sprycel is also an FDA-approved treatment for adults with newly diagnosed CP Ph+ CML (since October 2010). Sprycel received accelerated FDA approval for this indication. The effectiveness of Sprycel is based on cytogenetic response and major molecular response rates. The trial is ongoing and further data will be required to determine long-term outcome. Additional country approvals for this indication total more than 50.

About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the commercialization of Sprycel (dasatinib) in the United States, Japan, and major European countries. Sprycel was discovered and developed by Bristol-Myers Squibb.

For more information about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

For information about Otsuka Pharmaceutical Co., Ltd., visit www.otsuka-global.com.

1 Gleevec is a registered trademark of Novartis AG

2 Major molecular response (MMR) is defined as a BCR-ABL transcript level of ≤0.1% (3 log reduction) as measured by real-time quantitative polymerase chain reaction (RQ-PCR) of peripheral blood. These are cumulative rates representing minimum follow-up for the timeframe specified.

3 Complete cytogenetic response (CCyR) is defined as the absence of Philadelphia chromosome-positive metaphases on cytogenetic assessment of bone marrow cells.

4 Formal statistical comparison of cCCyR and MMR rates was only performed at the time of the primary endpoint (cCCyR within 12 months)

5 Hasford is a prognostic scoring system.

Contact:
Bristol-Myers Squibb
Media:
Melanie Brunner, 609-252-6338
melanie.brunner@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com
or
Otsuka
US:
Otsuka America Pharmaceutical Inc.
Rose Weldon, 609-524-6879
rose.weldon@otsuka-us.com
or
Japan:
Otsuka Pharmaceutical Co., Ltd.
Jeffrey Gilbert
gilbert.jeffrey@otsuka.co.jp
 

Posted: June 2013

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Sprycel (dasatinib) FDA Approval History

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