Vanda Pharmaceuticals' VGT-1849A Earns Orphan Drug Status for Polycythemia Vera Treatment

WASHINGTON, Dec. 20, 2024 – Vanda Pharmaceuticals Inc., a global biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has awarded Orphan Drug Designation for VGT-1849A. This novel medication is a selective antisense oligonucleotide (ASO)-based JAK2 inhibitor developed to treat polycythemia vera (PV), a rare type of blood cancer affecting approximately 1 in 2000 individuals in the United States.

Polycythemia vera is a chronic disorder of blood cell production characterized by excessive creation of red blood cells and increased levels of pro-inflammatory cytokines. A significant majority of PV patients, over 95%, possess the JAK2 V617F mutation, which leads to abnormal JAK2 production. Inhibition of JAK2 is crucial in curbing excessive blood cell production, subsequently reducing levels of red blood cells, neutrophils, platelets, and lymphocytes. In various hematologic malignancies that depend on JAK signaling, JAK2 inhibitors have proven effective, including for the treatment of PV. By precisely decreasing JAK2 levels, the ASO VGT-1849A aims to mitigate the harmful signaling driven by JAK2V617F, thereby hindering the malignant growth and persistence of blood cells.

Current treatments involving small molecule inhibitors of the JAK2 protein kinase, such as Jakafi®, Inrebic®, Ojjaara®, and Vonjo®, often lack specificity, potentially leading to side effects due to the inhibition of non-target proteins. The potential adverse effects associated with JAK inhibition underscore the importance of targeting JAK2 specifically to minimize risks related to infection and toxicity. This targeted approach hopes to avoid the inhibition of other kinases within the JAK family and beyond, such as JAK1, JAK3, and TYK2.

If VGT-1849A receives approval, it could offer a more targeted treatment option with improved safety and dosing convenience. The orphan designation for this drug represents a significant achievement in the field of precision medicine targeting hematologic malignancies, according to Mihael H. Polymeropoulos, M.D., Vanda's President, CEO, and Chairman of the Board. Additionally, this milestone follows the development of VCA-894A, designed for Charcot-Marie-Tooth disease, which is expected to enter clinical trials soon.

VGT-1849A is a cutting-edge ASO treatment candidate for PV and other JAK2-related blood cancers. By focusing on JAK2, VGT-1849A aims to reduce downstream signaling and autonomous cell proliferation driven by JAK2V617F, while avoiding unintended kinase effects. Its potential to decrease JAK2 activity could ease the burden on PV patients, enhancing their quality of life due to a favorable safety profile.

The FDA’s Orphan Drug Designation is intended for experimental therapies addressing rare diseases, providing benefits to developers for pursuing these treatments. Vanda Pharmaceuticals Inc. is committed to creating and commercializing innovative therapies to meet unmet medical needs and enhance patient lives.