Bristol-Myers Squibb announces its ongoing commitment to patients with chronic myeloid leukaemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL), and an exciting new phase of clinical investigation for SPRYCEL™ (dasatinib).

The announcement coincides with the presentation of updated data from the landmark START (SRC/ABL Tyrosine kinase inhibition Activity Research Trials of dasatinib) clinical trial programme at the 12th Congress of European Haematology, organised by the European Haematology Association (EHA), Vienna, Austria.

The START data provide longer term confirmation of the efficacy and safety of SPRYCEL treatment in patients with chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy, including imatinib, and in treatment resistant and intolerant patients with Ph+ ALL:

Chronic phase CML SPRYCEL provides lasting cytogenetic responses in patients with CP CML with resistance or intolerance to imatinib and a progression-free survival rate of 88%.1 In addition to being well tolerated and effective in patients resistant to conventional doses of imatinib, the data is consistently favourable to SPRYCEL over high- dose imatinib in resistant patients with chronic phase (CP) CML.2 Lymphoid blast CML and Ph+ ALL SPRYCEL continues to show efficacy in the treatment of Ph+ ALL following treatment failure with imatinib.3 Tolerability in CML and Ph+ ALL The safety and tolerability profile of SPRYCEL is consistent with previous studies and is both manageable and acceptable.1-3,4

In line with the START trial protocols and the successful collection of data, which demonstrate the studies have met their primary endpoints, Bristol-Myers Squibb confirms the end of the trial programme is nearing.

Study investigators have been informed and Bristol-Myers Squibb will ensure that trial patients responding to SPRYCEL will continue to receive the treatment.

"Bristol-Myers Squibb remains committed to patients with CML and Ph+ ALL and we are devoted to exploring the full potential of SPRYCEL in this disease area", comments Dr. Claude Nicaise, Head of Clinical Development for SPRYCEL, Bristol-Myers Squibb. "With the end of the START clinical trial programme nearing, we already have studies on-going and newer studies are in recruitment phase. As with all our clinical trials, we continue to be dedicated to achieving long-term data to ensure SPRYCEL provides the maximum benefits to patients."

Ongoing SPRYCEL studies:

Bristol-Myers Squibb is investigating the most beneficial dosing regimen for patients with CP CML. Recently updated results from two dose optimisation studies were presented this week at EHA.5,6

Designed to compare response rates and evaluate safety, overall the data show that once daily 100mg SPRYCEL offers a favourable regimen, providing optimal tolerability without compromising efficacy.6

New areas of investigation:

Bristol-Myers Squibb confirms: The expansion of a European open-label, randomized (2:1 ratio), multi-centre study CA 180-043 of SPRYCEL 100mg once-daily versus high-dose (800mg) imatinib in patients with suboptimal response to imatinib. The study will take place in 60 centres across Europe.
The company plans to discuss the initiation of large long-term global studies to investigate the potential of SPRYCEL as 1st line treatment in patients with CP CML with regulatory authorities in Europe and the US. The announcement follows the presentation of encouraging results from a small independent Phase II study at the recent American Society of Clinical Oncology (ASCO) and at EHA this week.7 Researchers from M.D. Anderson concluded that SPRYCEL may have a potential important role as a first-line therapy in CP CML. SPRYCEL has given renewed hope and life to patients across Europe through its ongoing clinical development and its rapid approval from the European Commission in November 2006.

START Clinical Trial Programme Data Update from the 12th Congress of European Haematology, organised by the EHA:

CHRONIC PHASE CML

Guilhot F et al. CA180013 (START C) - oral presentation, 08.30hrs CET Saturday 9 June, abstract 0358:1 The aim of the study was to establish the efficacy and safety of SPRYCEL in patients with CP CML with resistance or intolerance to imatinib. The follow up results of 15.2 months demonstrate lasting cytogenetic responses with SPRYCEL treatment with a progression-free survival rate of 88%. Following treatment failure with imatinib, 91% of patients treated with SPRYCEL achieved complete haematologic response (CHR). 59% and 49% of SPRYCEL patients achieved major cytogenetic response (MCyR) and complete cytogenetic response (CCyR), respectively. The response rates with SPRYCEL were higher than those seen with imatinib prior to treatment failure. Martinelli G et al. CA180017 (START R) - oral presentation, 09.00hrs CET Sunday 10 June, abstract 0862:2 The aim of the study was to evaluate SPRYCEL versus high-dose imatinib in patients with CP CML, after failure of standard dose imatinib. The study authors concluded that in addition to SPRYCEL being a well tolerated and effective therapy for CP CML patients who are resistant to conventional doses of imatinib, the data from START R provides evidence of SPRYCEL's benefit over high- dose imatinib for this patient population following failure of standard dose imatinib. Early, complete and lasting cytogenetic response with SPRYCEL with statistically significant difference between SPRYCEL and high-dose imatinib in progression-free survival and time to treatment failure. 93% of patients treated with SPRYCEL achieved CHR with 82% treated with high-dose imatinib. MCyR was seen in 52% of patients treated with SPRYCEL and 33% treated with high-dose imatinib. 40% of SPRYCEL patients reached complete cytogenetic response. 16% of patients achieved complete cytogenetic response with high-dose imatinib. Major molecular response was seen in 16% of patients treated with SPRYCEL whereas 4% of patients treated with imatinib achieved the same response. LYMPHOID BLAST CML AND Ph+ ALL

Ottmann O et al. CA180015 (START L) - poster presentation, 17.45hrs CET Friday 8 June, abstract 0026:3 The aim of the study was to establish the efficacy and safety of SPRYCEL in patients with Ph+ ALL following treatment failure with imatinib. The data conclude that SPRYCEL continues to show efficacy in this difficult-to-treat patient population. Overall major haematologic response (MaHR) rate was 41%, CCyR was seen in 54% and MCyR in 57% of patients. Median overall survival (OS) was 8.0 months, with 22% of patients remaining alive and progression-free after one year of treatment. Outcome was favourable for patients with prior stem cell transplant (SCT): median OS of 9.0 months (5.8 months for patients without prior SCT).

References:

1. Guilhot F et al. Dasatinib induces durable cytogenetic responses in patients with chronic-phase CML with resistance or intolerance to imatinib: updated results of the CA180013 (START C Trial). Abstract no. 0358. 9 June 2007, 12th Congress of European Haematology, organised by the European Haematology Association (EHA), Vienna, Austria.

2. Martinelli, G et al. Comparison of dasatinib to high-dose imatinib in patients who experience imatinib failure: results from a randomized Phase II trial (CA180017, START R). Abstract no. 0862. 10 June 2007, 12th Congress of European Haematology, organised by the European Haematology Association, Vienna, Austria.

3. Ottmann O et al. Dasatinib induces rapid and durable response in patients with Ph+ ALL resistant or intolerant to imatinib: updated results from CA180015 (START-L) Trial. Abstract no. 0026. 8 June 2007, 12th Congress of European Haematology, organised by the European Haematology Association, Vienna, Austria.

4. SPRYCELTM Summary of Product Characteristics.

5. Dombret H et al. Dasatinib 140 mg qd vs 70 mg bid in advanced-phase CML or PH(+) ALL resistant or intolerant to imatinib: results from a randomized, phase-III trial (CA180035). Abstract no. 0859. 10June 2007, 12th Congress of European Haematology, organised by the European Haematology Association (EHA), Vienna, Austria.

6. Hochhaus A, et al. Dasatinib dose and schedule optimization in chronic-phase cml resistant or intolerant to imatinib: results from a randomized phase-III trial (CA180034). Abstract no. 0359 9 June 2007, 12th Congress of European Haematology, organised by the European Haematology Association (EHA), Vienna, Austria.

7. Cardama Q A et al. Dasatinib is safe and effective in patients with previously untreated chronic myelogenous leukemia (CML) in chronic phase (CML-CP). Abstract no. 0360. 9 June 2007, 12th Congress of European Haematology, organised by the European Haematology Association (EHA), Vienna, Austria.

For further information please contact:
Yvette Venable
Bristol-Myers Squibb

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