Regulatory Affairs

EC approves expanded indication for BMS’ Sprycel

Published 06 July 2018

Bristol-Myers Squibb (BMS) has announced that the European Commission (EC) has expanded the indication for Sprycel (dasatinib) to include the treatment of children and adolescents aged 1 year to 18 years with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP), and to include a powder for oral suspension formulation.

The approval follows a positive opinion issued by the European Medicines Agency's Committee for Medicinal Products for Human Use on April 26, 2018, and makes Sprycel the first ever tyrosine kinase inhibitor to be approved in a powder formulation for administration in pediatric patients and patients who cannot swallow tablets.

The EC approval is based on data from CA180-226 (NCT00777036), the largest prospective trial evaluating the safety and efficacy of Sprycel in pediatric patients newly diagnosed with CP-CML, and in those resistant to or intolerant of imatinib.

“Treatment options for pediatric patients with CML are limited, as are formulations that correspond with the unique demands of children with cancer,” said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb.

 “Our decision to pursue an expanded indication for Sprycel in this new patient population and as a new formulation is indicative of our commitment to extending the potential of our medicines to address the unmet needs of patients with cancer, regardless of the incidence of the disease.”

In the Phase 2 CA180-226 trial, at minimum two-year follow-up, patients with CP-CML resistant to or intolerant of imatinib who received Sprycel demonstrated a cumulative major cytogenetic response (MCyR) rate of 55.2% (95% CI: 36, 74) 3 months into treatment, exceeding the defined threshold of clinical interest (>30%) for the primary endpoint of the cohort and increasing over time to greater than 90% (95% CI: 73, 98) at 24 months.

Newly diagnosed patients with CP-CML who received Sprycel as a tablet or as powder for oral suspension achieved a cumulative complete cytogenetic response (CCyR) rate, the primary endpoint in the cohort, of 64% (95% CI: 53, 74) as early as 6 months into treatment, exceeding the defined threshold of clinical interest (>55%) and increasing over time to 94% (95% CI: 87, 98) at 24 months. The secondary endpoint of estimated progression-free survival at 48 months was greater than 75% for patients resistant to or intolerant of imatinib and greater than 90% for patients who received Sprycel as a first-line therapy.

Sprycel was shown to have a comparable safety profile in pediatric patients with CP-CML to that reported in adults with CP-CML. The most commonly reported adverse events in newly diagnosed patients treated with Sprycel were nausea/vomiting (20%), rash (19%) and diarrhea (18%), and in imatinib-intolerant or -resistant patients were nausea/vomiting (31%), myalgia/arthralgia (17%), fatigue (14%) and rash (14%). In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension or pulmonary arterial hypertension related to Sprycel. Study results were published in the Journal of Clinical Oncology in March 2018.

The recommended starting dosage for Sprycel in pediatric patients with Ph+ CP-CML is based on body weight. The Sprycel powder for oral suspension (PFOS) is for patients weighing 10 kg or less, or who cannot swallow tablets whole. The recommended dose for both the tablet and PFOS formulations should be recalculated every three months based on changes in body weight, or more often if necessary.

Sprycel tablets should be swallowed whole and should not be crushed, cut or chewed. The exposure in patients receiving a crushed tablet is lower than in those swallowing an intact tablet. The Sprycel tablet and PFOS formulations are not bioequivalent. Patients should only switch between the tablet and PFOS formulations at the discretion of a medical professional, who will decide the right formulation and dose based on the patient’s weight.

Sprycel first received 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 and marketed for these indications in more than 60 countries.

Source: Company Press Release