United States securities and exchange commission logo January 26, 2021 Elizabeth Hougen Chief Financial Officer Ionis Pharmaceuticals, Inc. 2855 Gazelle Court Carlsbad, California Re: Ionis Pharmaceuticals, Inc. Form 10-K for the Fiscal Year Ended December 31, 2019 Filed March 2, 2020 File No. 000-19125 Dear Ms. Hougen: We have completed our review of your filing. We remind you that the company and its management are responsible for the accuracy and adequacy of their disclosures, notwithstanding any review, comments, action or absence of action by the staff. Sincerely, Division of Corporation Finance Office of Life Sciences