The Mechanism of Action of SAR302503

Tal Zaks, MD, PhD, vice president and head of development at Sanofi Oncology, explains the mechanism of action of SAR302503, a tyrosine kinase inhibitor being investigated in a phase III trial in patients with intermediate-2 or high-risk myelofibrosis.

Zaks explains that when a mutation in the JAK/STAT pathway is present, JAK2 is hyperactivated, causing abnormal intracellular signaling and abnormal blood proliferation and production. SAR302503 inhibits enzymatic activity and blocks abnormal signaling.

Clinical Pearls

When testing a patient's blood, Zaks says, it becomes evident where the signaling pathway is hyperactivated and where the drug blocks signaling. It is this link between the molecular rational design of the drug that will inhibit the pathway and culminate in the clinical benefit of symptom amelioration. Zaks hopes, in the long run, that there will be a change in the pathophysiology of this disease so that patients feel better and the drug reverts the disease process so that patients can live longer.

• SAR302503 is being investigated in a phase III trial in patients with intermediate-2 or high-risk myelofibrosis
• SAR302503 is a TKI that inhibits enzymatic activity, blocking abnormal signaling