Date: 2012-12-09
Type of information:
phase: 2
Announcement: presentation of phase 2 data at the 2012 Annual Meeting of the American Society of Hematology (ASH)
Company: Sanofi (France)
Product: SAR302503
Action
mechanism: Mutations in JAK2 can lead to dysregulated JAK2 signaling and are thought to be a cause of myelofibrosis. Patients with wild type JAK2 have also been shown to have persistent, dysregulated activation of the JAK2 signaling pathway. SAR302503 is a novel, investigational, selective inhibitor of the JAK/STAT signaling pathway that
preferentially inhibits a key enzyme for blood cell development, JAK2. Sanofi Oncology is developing the compound for the treatment of the three main types of myeloproliferative neoplasms: primary myelofibrosis, polycythemia vera and essential thrombocythemia. Sanofi is also studying the effect of the compound on reducing/reversing scarring in the bone marrow.
Disease: myelofibrosis
Therapeutic area: Cancer - Oncology - Blood diseases - Hematological diseases
Country:
Trial
details: The Phase II, open label, randomized dose-ranging study evaluates the efficacy of once-daily oral doses of 300 mg, 400 mg, and 500 mg of SAR302503 for the reduction of spleen volume. The primary endpoint is change in spleen volume at the end of cycle three assessed by MRI with independent central review. Secondary endpoints include spleen response (reduction in spleen volume greater than or equal to 35 percent vs. baseline), safety and symptom response using the MPN-SAF scale.
Latest
news: * On December 9, 2012, Sanofi has announced new Phase II data showing that treatment with a novel, investigational, selective JAK2 inhibitor (SAR302503) reduced spleen size and improved constitutional symptoms in patients with intermediate-2 or high-risk primary or secondary myelofibrosis (MF), a hematologic malignancy with unmet medical needs. The data were presented during the 2012 Annual Meeting of the American Society of Hematology. Results from this Phase II trial support the two doses (400 mg and 500 mg) selected for the SAR302503 Phase III JAKARTA trial that is currently under way. JAKARTA enrolled 289 patients over nine months and initial results are expected in the second quarter of 2013.
According to the study results, treatment was associated with reductions in spleen size and other disease symptoms in 31 randomized patients.
• Mean percentage reductions in spleen volume vs. baseline were 30% (n=10), 33% (n=10) and 42% (n=11), in each group, respectively
• The proportion of patients who achieved a ?35% reduction in spleen volume by MRI was 30%, 50% and 63.6% in each group, respectively.
• The proportion of patients who achieved ?50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) score, a sum of six key constitutional symptoms (night sweats, itching, abdominal discomfort, abdominal pain, bone pain, early satiety), was similar in all dose groups (44%, 50% and 44%).
Consistent with data reported in previous trials, the most common serious (grade 3-4) hematologic adverse event was anemia with rates across the 300, 400, and 500 mg doses of 33%, 30% and 55%, respectively. Rates of grade 3-4 thrombocytopenia were 20%, 0% and 9%, respectively.
The most common grade 3-4 non-hematological events were diarrhea (10%, 20%, 0%), nausea (10%, 10%, 0%) and vomiting (10%, 10%, 0%). Two patients in the 300 mg group discontinued treatment due to an adverse event (grade 3 anemia, grade 4 transaminase elevation).
