PRINCETON, N.J.–(BUSINESS WIRE)–Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel ® (dasatinib) tablets to include the treatment of pediatric patients one year of age and older with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in combination with chemotherapy.1 Sprycel is the only second-generation tyrosine kinase inhibitor approved for this patient population. The approval, which was granted following priority review by the FDA, is based on data from the Phase 2 study, CA180-372 (NCT01460160).
“We recognize the urgency around developing and delivering therapies for children and young adults living with cancer, and today’s approval is an important example of our commitment to pediatric oncology,” said Jeffrey Jackson, Ph.D., development lead, hematology, Bristol-Myers Squibb. “Building on our previous indication for children with Ph+ chronic myeloid leukemia in chronic phase, we’re pleased to bring Sprycel tablets to a second type of pediatric leukemia. This approval will give physicians another treatment option to offer appropriate pediatric patients with Ph+ ALL.”
Sprycel is associated with the following Warnings and Precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity and effects on growth and development in pediatric patients.1 Please see detailed Important Safety Information below.
The efficacy of Sprycel tablets in combination with chemotherapy was evaluated in a single cohort of the Phase 2, multicenter, single-arm CA180-372 study, which included 78 pediatric patients with newly diagnosed B-cell precursor Ph+ ALL.1,2 At three years, the study demonstrated an event-free survival (EFS) binary rate of 64.1% (95% confidence interval [CI]: 52.4 to 74.7).1 Event-free survival is defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.
Of the 81 patients evaluated for safety, fatal adverse reactions occurred in three patients (4%), and eight (10%) experienced adverse reactions leading to treatment discontinuation, including fungal sepsis, hepatotoxicity of graft versus host disease, thrombocytopenia, CMV infection, pneumonia, nausea, enteritis and drug hypersensitivity.1 The most common serious adverse reactions (incidence ≥10%) were pyrexia, febrile neutropenia, mucositis, diarrhea, sepsis, hypotension, infections (bacterial, viral and fungal), hypersensitivity, vomiting, renal insufficiency, abdominal pain and musculoskeletal pain.1
“As treatments have advanced in recent years, we’ve seen improvements in outcomes for pediatric patients with Ph+ ALL overall, but there remains a need for additional options,”3 said Stephen Hunger, MD, lead study author, chief of the division of oncology and director of the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia. “The Phase 2 CA180-372 trial was particularly informative because it was designed to limit the use of cranial irradiation and stem cell transplant. In the study, Sprycel plus chemotherapy demonstrated a three-year event-free survival benefit. These results show that Sprycel is an effective medication for physicians to consider for children and adolescents with Ph+ ALL.”1,4
Acute lymphoblastic leukemia is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells.5 The most common childhood cancer in the United States, ALL represents 20% of all cancers diagnosed in persons aged less than 20 years, or more than 3,000 new cases each year.6 Three percent of children who have ALL have the Ph+ subtype, which means they have a chromosome alteration that results in a specific mutation of the BCR-ABL gene.3
“Coping with a pediatric cancer diagnosis, including searching for and identifying the right treatment regimen, can take a physical and emotional toll on patients and their families,” said Vickie Buenger, president of the Coalition Against Childhood Cancer (CAC2). “The availability of another option is a welcome step forward for those affected by this disease.”
In addition to this pediatric approval, Sprycel is approved for use in children one year of age and older with Ph+ chronic myeloid leukemia (CML) in chronic phase (CP).1
About the Phase 2 CA180-372 Study
In the CA180-372 trial, the 78 patients evaluated for efficacy in cohort 1 received Sprycel at a daily dose of 60 mg/m2 for up to 24 months, in combination with chemotherapy.1 The backbone chemotherapy regimen was the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol.1 Efficacy was established based on three-year EFS, defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.1 The trial was designed such that patients with central nervous system 3 disease receive cranial irradiation.4 Patients were assigned to receive stem cell transplant (SCT) based on minimal residual disease if they were considered high-risk.4 Data from the CA180-372 trial were presented at the 2017 American Society of Hematology Annual Meeting.
The recommended starting dosage for Sprycel in pediatric patients with Ph+ ALL is based on body weight.1 The recommended dose should be administered orally once daily, and the dose should be recalculated every three months based on changes in body weight, or more often if necessary.1 For pediatric patients with Ph+ ALL, Sprycel therapy should begin on or before day 15 of induction chemotherapy, when diagnosis is confirmed, and continue for two years.1
Sprycel tablets should not be crushed, cut or chewed.1 Tablets should be swallowed whole; however, there are additional administration considerations for pediatric patients who have difficulty swallowing tablets whole.1 Five patients with Ph+ ALL 2 to 10 years of age received at least one dose of Sprycel tablet dispersed in juice on Study CA180-372. The exposure for dispersed tablets was estimated to be 36% lower as compared to intact tablets in pediatric patients. Due to the limited available clinical data, it is unclear whether dispersing Sprycel tablets significantly alters the safety and/or efficacy of Sprycel.
Select Safety Profile for the CA180-372 Study
In the CA180-372 study, 81 pediatric patients with Ph+ ALL received Sprycel continuously in combination with chemotherapy.1 The median duration of therapy was 24 months (range 2 to 27 months).1
Among these patients, the most common adverse reactions (reported in at least 20% of patients) were mucositis (93%), febrile neutropenia (86%), pyrexia (85%), diarrhea (84%), nausea (84%), vomiting (83%), musculoskeletal pain (83%), abdominal pain (78%), cough (78%), headache (77%), rash (68%), fatigue (59%), constipation (57%), arrhythmia (47%), hypertension (47%), edema (47%), viral infection (40%), hypotension (40%), decreased appetite (38%), hypersensitivity (36%), upper respiratory tract infection (36%), dyspnea (35%), epistaxis (31%), peripheral neuropathy (31%), altered state of consciousness (30%), fungal infection (30%), pneumonia (excluding fungal) (28%), pruritus (28%), Clostridial infection (excluding sepsis) (25%), urinary tract infection (24%), bacteremia (excluding fungal) (22%), erythema (22%), chills (21%), pleural effusion (21%), sinusitis (21%), dehydration (20%), renal insufficiency (20%) and visual impairment (20%).1
Sprycel® (dasatinib) is indicated for the treatment of adult patients with:
- Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase
- Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy
Sprycel is indicated for the treatment of pediatric patients 1 year of age and older with:
- Ph+ CML in chronic phase
- Newly diagnosed Ph+ ALL in combination with chemotherapy
Sprycel (100 mg) is a tablet.
Sprycel first received FDA approval in 2006 for the treatment of adults with Ph+ CML in CP who are resistant or intolerant to prior therapy including imatinib. At that time, Sprycel was also approved for adults with Ph+ ALL who are resistant or intolerant to prior therapy. Sprycel is approved and marketed worldwide for these indications in more than 60 countries.
Sprycel is also an FDA-approved treatment for adults with newly diagnosed CP Ph+ CML, and in November 2017, Sprycel received FDA approval for the expanded indication for treatment in pediatric patients with CP Ph+ CML. The adult indication is approved in more than 50 countries.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2017, as updated by our subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by federal securities law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
Source: Bristol-Myers Squibb Company
Posted: January 2019
- FDA Expands Approval of Sprycel (dasatinib) to Include Treatment of Children with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase – November 10, 2017
- 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 – June 21, 2013
- FDA approves additional medical indication for Sprycel – October 28, 2010
- FDA Grants Full Approval for Sprycel (dasatinib) for the Treatment of Adults with Chronic Myeloid Leukemia Who Are Resistant or Intolerant to Prior Therapies Including Gleevec – May 26, 2009
- FDA Approves New Sprycel (Dasatinib) Product Labeling for Patients
with Chronic-Phase CML – November 9, 2007
- Sprycel Bristol-Myers Squibb Company – Treatment for Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (Ph+ALL) – June 28, 2006
- Bristol-Myers Squibb Issues Statement on Oncologic Drugs Advisory Committee Vote in Favor of Investigational Drug Dasatinib – June 2, 2006
- FDA Grants Priority Review for Bristol-Myers Squibb’s Investigational Oncology Treatment Dasatinib – March 7, 2006
- Bristol-Myers Squibb Submits New Drug Application for Dasatinib – December 28, 2005
Sprycel (dasatinib) FDA Approval History
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