|ARRY-614 Demonstrates Positive Single Agent Activity in Patients with Myelodysplastic Syndromes|
"I am excited about the results of the Phase 1 study with ARRY-614,
which was well-tolerated in lower risk MDS patients,” said Rami S.
Komrokji, M.D., Clinical Director, Hematologic Malignancies,
Phase 1 Dose-Escalation/Expansion Study of the p38/Tie2 Inhibitor
ARRY-614 in Patients with IPSS Low/Int-1 Risk Myelodysplastic Syndromes
In this Phase 1 dose-escalation/expansion study (N=45), ARRY-614 demonstrated clinical activity as a single agent in patients with International Prognostic Scoring System (IPSS) Low or Intermediate-1 risk MDS and in whom treatments with approved therapies have failed, including hypomethylating agents and lenalidomide. As shown below in the chart, there was a 38% response rate for hematologic improvement (HI) in patients receiving drug at the highest dose, 1200 mg daily (n=16). At this dose, ARRY-614 demonstrated multilineage HI in 67% of the responders, improving more than one cytopenia: neutropenia, thrombocytopenia and/or anemia. HI was demonstrated in 30% of all patients and generally increased with increasing total daily dose from 400 mg to 1200 mg.
HI with ARRY-614 was durable, with multiple patients remaining on therapy for over nine months. The maximum tolerated dose was not reached at the once-daily oral doses studied; the most common adverse events were rash and diarrhea; clinically significant hematologic toxicity was minimal. Observed changes in pharmacodynamic markers in patients with MDS treated with ARRY-614 included p38-dependent normalization of plasma erythropoietin, as well as decreases in phospho-p38 and disease-related apoptosis in the bone marrow.
About Myelodysplastic Syndromes, Dual p38/Tie2 Inhibition and ARRY-614
Myelodysplastic syndromes are a heterogeneous group of clonal bone marrow cancers that are characterized by a loss of normal blood cells and a variable risk of progression to acute myeloid leukemia. Patients with MDS, who have limited treatment options, often suffer from fatigue, bleeding events, cardiovascular issues and potentially fatal infections. This disease has a high economic and quality of life burden due to frequent transfusions. MDS is a considerably under-diagnosed cancer. Recent studies estimate there are up to 45,000 new cases annually in the U.S.
Bone marrow of patients with MDS is characterized by excessive levels of myelosuppressive cytokines and the presence of an abnormal clone, and bone marrow stress from hypoxia and aging. These stressors can cause cell death of progenitors and support cells, resulting in anemia, neutropenia and/or thrombocytopenia.
ARRY-614’s dual p38/Tie2 inhibition is a unique mechanism of action for the treatment of MDS. p38 and Tie2 are overactivated in the bone marrow of patients with MDS. ARRY-614 enables the hematopoietic repopulation of red blood cells, platelets and neutrophils and is believed to restore bone marrow function by blocking myelosuppression. This drug has demonstrated hematologic improvement in patients with MDS for whom hypomethylating agents have failed and now have no approved treatment options. In addition, ARRY-614 was generally well tolerated in a Phase 1 study with minimal hematologic toxicity. A new formulation of ARRY-614 with improved exposure and lower inter-subject variability is currently being investigated in a Phase 1 clinical trial in patients with MDS.
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements about the potential for the results of ongoing
preclinical and clinical trials to support further development, and
regulatory approval or the marketing success, of a drug candidate, and
our future plans to progress and develop our proprietary programs,
including ARRY-614. These statements involve significant risks and
uncertainties, including those discussed in our most recent annual
report filed on form 10-K, in our quarterly reports filed on Form 10-Q,
and in other reports filed by Array with the