Dear global HD patient community, Today we are sharing an important update to the study design of the global Phase III GENERATION HD1 study (NCT03761849) evaluating the efficacy and safety of the investigational medicine RG6042 (formerly known as IONIS-HTTRx) for manifest Huntington’s disease (HD). Preliminary data from the ongoing open-label extension of the Phase I/IIa study (NCT03342053) support continued evaluation of RG6042 as a potential treatment for HD. These data also enable GENERATION HD1 design changes that we believe will make study participation less demanding for patients, their families and healthcare providers. The 15-month open-label extension of the Phase I/IIa study is evaluating RG6042 treatment in doses every month (every four weeks) and every two months (every eight weeks). Review of nine-month data showed effects on lowering mutant huntingtin protein levels in the cerebral spinal fluid that support the exploration of less frequent dosing. Based on the totality of the data, including safety and tolerability, there appears to be no overall advantage to treatment monthly versus every two months. The open-label extension of the Phase I/IIa study will be completed as planned, and detailed results will be shared at an upcoming scientific meeting. While it is important to note that these are early data from an open-label study and it is not appropriate to draw conclusions about clinical efficacy or longer-term safety, we are pleased that these data support the GENERATION HD1 study design changes described below. Key changes to the GENERATION HD1 study The study arms involving treatment every two months and placebo will remain, however the study arm that tests monthly treatment will be replaced with one that tests a less frequent dose of once every four months (every 16 weeks).