Vanda Pharmaceuticals Introduces Novel Orphan Drug VGT-1849A for the Treatment of Polycythemia Vera
Vanda Pharmaceuticals has announced that the U.S. Food and Drug Administration has granted Orphan Drug Designation for VGT-1849A, a selective antisense oligonucleotide (ASO)-based JAK2 inhibitor. This investigational therapy is being developed for polycythemia vera (PV), a rare blood disorder affecting approximately 1 in 2,000 individuals in the United States.
Polycythemia vera is a chronic myeloproliferative disorder characterised by abnormal blood cell production, particularly an excessive increase in red blood cells, as well as elevated levels of pro-inflammatory cytokines. Over 95% of those diagnosed with PV carry the JAK2 V617F mutation, which leads to uncontrolled production of JAK2, a key protein in blood cell development.
By inhibiting JAK2, VGT-1849A aims to regulate blood cell production, thereby reducing the levels of red cells, neutrophils, platelets, and lymphocytes. JAK2 inhibitors have demonstrated efficacy in treating various haematological cancers linked to JAK mutations, including PV. VGT-1849A, through its selective targeting of JAK2, seeks to mitigate the harmful effects caused by the JAK2 V617F mutation and limit the proliferation of abnormal blood cells.
Current JAK2 inhibitors on the market, such as Jakafi®, Inrebic®, Ojjaara®, and Vonjo®, lack specificity for JAK2 alone, which may lead to unintended effects by also inhibiting other members of the JAK family or unrelated kinases. This broad inhibition can cause adverse effects, underscoring the need for a treatment that exclusively targets JAK2. VGT-1849A's selective approach aims to reduce the risk of infection and toxicity that may arise from broader JAK inhibition, potentially improving patient safety and treatment outcomes.
If approved, VGT-1849A could provide a more targeted treatment option with enhanced safety and convenient administration.
The Orphan Drug Designation for VGT-1849A represents a significant step in the development of precision medicines for haematological disorders. This candidate follows Vanda’s previous precision therapy, VCA-894A, designed for Charcot-Marie-Tooth disease, which is expected to enter clinical trials shortly.
As an innovative ASO therapy, VGT-1849A focuses on reducing JAK2 activity without interfering with other kinases, aiming to relieve the disease burden faced by PV patients. With its targeted mechanism and potentially favourable safety profile, the therapy could enhance the quality of life for those living with PV.
The FDA grants Orphan Drug Designation to treatments addressing rare diseases, offering various benefits to developers to support the advancement of such therapies.
