Table 4.

Summary of C9ORF72 Therapeutics and Clinical Trials working group discussion

C9ORF72 Therapeutics and Clinical Trials working group
1. Develop trials targeting pre-symptomatic gene mutation carriers. Determine which C9ORF72 carriers are most likely to develop disease based on identification of risk/susceptibility biomarkers, given that penetrance is incomplete for the mutation. Determine which carriers will develop which syndrome
2. Develop basket or platform trials that include both ALS and FTD patients and that share a placebo group
3. Develop trials powered for changes in neurofilament but pair the neurofilament measurements with other measures specific to C9ORF72 if possible. While neurofilament is reasonably likely to predict clinical benefits, it is not a validated surrogate endpoint
4. Focus on C9ORF72 modulation first because the cause is known. Therapeutics that resolve both sense and antisense foci, while preserving C9ORF72 levels and normal function, are desirable
5. Develop and validate tools, including smartphone/watch apps, to track cognitive dysfunction by measuring digital endpoints, and use at-home patient measurements to get more dynamic readouts
6. Consider patient concerns regarding the existential threat that carrying C9ORF72 poses, as well as potential data privacy fears. Patients who are C9ORF72 carriers and still asymptomatic or pre-symptomatic have risks to their health insurance due to their C9ORF72 status
7. Incentivize investments in these rare disease spaces through offering market exclusivity and patent extensions