We are pleased to relay an update from Roche regarding GENERATION HD1, the Phase 3 study of RG6042 (IONIS-HTTRx) in patients with manifest Huntington’s disease. Based on a recent analysis of monthly and bi-monthly dosing in the Phase 2 open-label study, Roche has decided to replace the monthly dosing arm of the pivotal study with a tri-annual (every 4 months) dosing arm. The nine-month data from the open-label study demonstrated mutant huntingtin (mHTT) reduction with bi-monthly dosing that was robust and durable enough to support the evaluation of even 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. We believe this change to the pivotal study design will greatly simplify the operation of the study and ease the burden on study sites, as less frequent dosing is more manageable for patients and physicians.
There will be a temporary pause in the enrollment of new patients into the study. Once the protocol amendment is fully approved and in place, enrollment will re-open. Roche expects to begin randomizing patients under the amended protocol by the end of Q2 2019. Although this introduces a slight delay in the study, by easing the burden on study sites and patients with less frequent dosing, we don’t expect this delay will change the timing of study completion, and may even accelerate time to study completion.
We and Roche are encouraged by the performance of RG6042 (IONIS-HTTRx) to date and believe the changes described above will increase the probability of success for this important medicine for patients with this fatal, progressive neurodegenerative disease.