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Chemistry: Generation 2+ LICA

Sapablursen, formerly known as IONIS-TMPRSS6-LRx, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transmembrane protease, serine 6, or TMPRSS6, in patients with polycythemia vera. Polycythemia vera is caused by a mutation in the JAK2 gene and results in excessive production of red blood cells. TMPRSS6 is a protein produced in the liver that plays an important role in the production of the iron regulatory hormone hepcidin. Hepcidin reduces iron absorption from the gut and reduces iron re-cycling in the body. Overall, increased hepcidin production reduces the number of red blood cells that are produced and represents a novel treatment strategy for polycythemia vera. Results from preclinical studies confirm that sapablursen controls excessive red blood cell production in a model of polycythemia vera. 

About Polycythemia Vera  

Polycythemia vera (PV) is a type of chronic blood cancer characterized by excessive production of blood cells in the bone marrow, primarily red blood cells. Affected individuals may also have excess white blood cells and excess blood clotting cells called platelets. These extra cells cause the blood to be thicker than normal. As a result, abnormal blood clots are more likely to form and block the flow of blood through arteries and veins. Individuals with PV have an increased risk of deep vein thrombosis, a type of blood clot that occurs in the deep veins of the arms or legs. If a blood clot travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism. Affected individuals also have an increased risk of heart attack and stroke caused by blood clots in the heart and brain blood vessels. 

PV typically develops in adulthood, around age 60, although it may occur in younger individuals. This condition may not cause any symptoms in its early stages. Some people with PV experience headaches, fatigue, dizziness, ringing in the ears, impaired vision, night sweats, and red or itchy skin, especially after warm showers. Other complications of PV include an enlarged spleen, stomach ulcers, gout, heart disease, and progression into a more aggressive cancer like leukemia. 

 The prevalence of PV varies worldwide. The condition affects approximately 160,000 people in the United States. For unknown reasons, men develop PV more frequently than women. In the majority of PV cases, a specific genetic variant known as a JAK2 mutation can be found, which can be used to identify and confirm the disease.