U.S. Food and Drug Administration Expands Approval of Sprycel® (dasatinib) to Include Treatment of Children with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase

Sprycel is the first and only second-generation tyrosine kinase inhibitor approved for children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase

Approval based on data from the largest prospective trial in pediatric chronic myeloid leukemia in chronic phase 1

PRINCETON, NJ, USA I November 10, 2017 I 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 children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).1 This approval for Sprycel in pediatric patients with Ph+ CML in chronic phase was granted under priority review, and the indication received orphan drug designation from the FDA. The safety and efficacy of Sprycel in pediatric patients was evaluated in two pediatric studies of 97 patients with CP-CML: an open-label, non-randomized, dose-ranging trial (NCT00306202) and an open-label, non-randomized, single-arm trial (NCT00777036). Among the 97 patients in the two studies, 51 patients (exclusively from the single-arm trial) had newly diagnosed CP-CML, and 46 patients (17 from the dose-ranging trial and 29 from the single-arm trial) were resistant or intolerant to previous treatment with imatinib.1

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.

“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,”2,3 said Vickie Buenger, President, Coalition Against Childhood Cancer. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”

“Our decision to pursue an expanded indication for Sprycel is indicative of our commitment to exploring pediatric applications within our broad development program,” said Johanna Mercier, head, U.S. Commercial, Bristol-Myers Squibb. “We are pleased this option is now available for appropriate pediatric chronic phase CML patients and their physicians.”

As part of its commitment to children and adolescents with cancer, Bristol-Myers Squibb continues to explore pediatric applications for investigational oncology agents within its broad development program. In addition, Bristol-Myers Squibb supports organizations and initiatives focused on pediatric patients and their families.

“Options for pediatric patients with chronic myeloid leukemia are limited, and it is challenging to conduct clinical trials investigating potential new treatments in this small patient population,” said Lia Gore, M.D., University of Colorado School of Medicine and Children’s Hospital Colorado. “Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase.”

About the Sprycel Studies in Pediatric Patients

Sprycel was evaluated in two pediatric studies of 97 patients with CP-CML, including patients who were newly diagnosed and those who were resistant or intolerant to previous treatment with imatinib. Ninety-one of the 97 pediatric patients with CP-CML were treated with Sprycel tablets 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The efficacy endpoints included complete cytogenetic response (CCyR), major cytogenetic response (MCyR) and major molecular response (MMR).1 Efficacy results for the two pediatric studies are summarized in the table below.

 
Efficacy of Sprycel in Pediatric Patients with CP-CML Cumulative Response over Time by
Minimum Follow-Up Period
    3 Months   6 Months   12 Months   24 Months

CCyR

(95% CI)

               
Newly diagnosed   43.1%   66.7%   96.1%   96.1%
(N = 51)a   (29.3, 57.8)   (52.1, 79.2)   (86.5, 99.5)   (86.5, 99.5)
Prior imatinib   45.7%   71.7%   78.3%   82.6%
(N = 46)b   (30.9, 61.0)   (56.5, 84.0)   (63.6, 89.1)   (68.6, 92.2)
MCyR                
(95% CI)                
Newly diagnosed   60.8%   90.2%   98.0%   98.0%
(N = 51)a   (46.1, 74.2)   (78.6, 96.7)   (89.6, 100)   (89.6, 100)
Prior imatinib   60.9%   82.6%   89.1%   89.1%
(N = 46)b   (45.4, 74.9)   (68.6, 92.2)   (76.4, 96.4)   (76.4, 96.4)
MMR                
(95% CI)                
Newly diagnosed   7.8%   31.4%   56.9%   74.5%
(N = 51)a   (2.2, 18.9)   (19.1, 45.9)   (42.2, 70.7)   (60.4, 85.7)
Prior imatinib   15.2%   26.1%   39.1%   52.2%
(N = 46)b   (6.3, 28.9)   (14.3, 41.1)   (25.1, 54.6)   (36.9, 67.1)
a Patients from pediatric study of newly diagnosed CP-CML receiving oral tablet formulation
b Patients from pediatric studies of imatinib-resistant or -intolerant CP-CML receiving oral tablet formulation
   

With a median follow-up of 4.5 years in newly diagnosed patients, the median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off. Range of duration of response was (2.5+ to 66.5+ months for CCyR), (1.4 to 66.5+ months for MCyR) and (5.4+ to 72.5+ months for subjects who achieved MMR by month 24 and 0.03+ to 72.5+ months for subjects who achieved MMR at any time), where ‘+’ indicates a censored observation.

With a median follow-up of 5.2 years in imatinib-resistant or -intolerant patients, the median durations of CCyR, MCyR and MMR could not be estimated, as more than half the responding patients had not progressed at the time of data cut-off. Range of duration of response was (2.4 to 86.9+ months for CCyR), (2.4 to 86.9+ months for MCyR) and (2.6+ to 73.6+ months for MMR), where ‘+’ indicates a censored observation.

Drug-related serious adverse events were reported in 14.4% of Sprycel-treated pediatric patients with Ph+ CML in chronic phase. Most common adverse reactions (≥15%) included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremity and abdominal pain.

The recommended starting dosage for Sprycel in pediatric patients with Ph+ CML in chronic phase is based on body weight. 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 Sprycel tablets should not be crushed, cut or chewed. Tablets should be swallowed whole. The exposure in patients receiving a crushed tablet is lower than in those swallowing an intact tablet.

About Chronic Myeloid Leukemia

Chronic myeloid leukemia is a type of leukemia in which the body produces an uncontrolled number of abnormal white blood cells.4 Chronic myeloid leukemia occurs when pieces of two different chromosomes (chromosomes 9 and 22) break off and attach to each other.5 The newly formed chromosome is called the Philadelphia chromosome, which contains an abnormal gene called the BCR-ABL gene. This gene produces the BCR-ABL protein that signals cells to make too many white blood cells.5 There is no known cause for the genetic change that results in CML.6

About Sprycel

Sprycel first received U.S. Food and Drug Administration (FDA) approval in 2006 for the treatment of adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) who are resistant or intolerant to prior therapy including imatinib. At that time, Sprycel also received FDA approval for adults with Ph+ acute lymphoblastic leukemia (ALL) who are resistant or intolerant to prior therapy. Sprycel is approved for these indications in more than 60 countries.

In October 2010, Sprycel received accelerated FDA approval for the treatment of adults with newly diagnosed Ph+ CML in chronic phase. This indication is approved in more than 50 countries.

SPRYCEL ® (dasatinib) INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

SPRYCEL® (dasatinib) is indicated for the treatment of adults 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 with:

  • Ph+ CML in chronic phase.

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.

SOURCE: Bristol-Myers Squibb

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