Endpoints are the measures a trial uses to decide whether a drug did something. In prion disease the choice is hard, because the illness is rare and usually runs for months. The sections below set out what is registered, as read on 31 October 2026, and what is not established.
What did earlier trials measure?
Seven completed drug trials, summarised by cureffi.org, enrolled 360 people. Six used survival as the primary endpoint. The seventh, a flupirtine trial in Germany, used a cognitive scale (ADAS-Cog) and reported slower decline, but the drug did not become standard care. The other six reported negative results, or positive ones that investigators attributed to confounders. Survival depends on when in the illness a person enrols, which makes it hard to compare across small groups.
What do the current PrP-lowering trials measure?
| Trial | Primary outcome | Selected secondary outcomes |
|---|---|---|
| PrProfile (ION717, Ionis) | Treatment-emergent adverse events, baseline to Week 33 | Percent change from baseline in CSF PrP; drug concentrations in plasma and CSF |
| PrP-siRNA safety and mechanism study (Broad Institute) | Frequency of adverse events, baseline to Week 24 | CSF PrP at 4, 8, 12 and 24 weeks; change in CSF PrP over time; plasma and CSF drug concentration |
| ALN-6457 (Regeneron) | Adverse events and their severity through Week 156; percentage change in plasma neurofilament light chain (NfL) through Week 130 | CSF PrP; drug concentrations; overall survival rate at Week 52 |
CSF PrP, the concentration of prion protein in spinal fluid, is a pharmacodynamic measure. It shows whether a drug is lowering its target. The registry records do not claim that a fall in CSF PrP predicts clinical benefit. NfL is a blood marker of nerve cell injury. Its use as a primary outcome in the ALN-6457 record is the sponsor’s choice, and the records read here do not report data on how well it tracks clinical course in prion disease.
Which clinical scales are in use?
The Broad Institute record uses the MRC Prion Disease Rating Scale to define eligibility for symptomatic participants, requiring a score of 15 or more, and the MRC score and the Montreal Cognitive Assessment (MoCA) to describe pre-symptomatic participants. The records read do not list a clinical rating scale as a primary or secondary outcome for the other two trials.
What is unknown?
- Whether any registered biomarker predicts survival or function. None of the records reports efficacy data.
- Whether a trial with a safety primary outcome and 45 to 85 participants can detect benefit. The sponsors describe these as early studies.
- Which measures regulators would accept as evidence of benefit in prion disease. The regulatory pathway page covers orphan designation but not accepted endpoints.
For the programmes themselves, see the pipeline overview, and for recruitment context see trial feasibility.
Sources for this page
- ClinicalTrials.gov NCT06153966: PrProfile, a study of ION717 (record updated 18 September 2026)
- ClinicalTrials.gov NCT07832370: a trial of ALN-6457 in symptomatic prion disease (record updated 22 September 2026)
- ClinicalTrials.gov NCT07444580: PrP-targeting siRNA safety and mechanism study (record updated 16 October 2026)
- cureffi.org: Completed clinical trials in prion disease (15 April 2015)