# Mivelsiran (ALN-APP) by Alnylam Pharmaceuticals

Canonical page: https://technooptimist.io/biotech/mivelsiran
Frontier: [Biotech](https://technooptimist.io/biotech.md) · Field: RNAi & antisense drugs · Company: [Alnylam Pharmaceuticals](https://technooptimist.io/companies/alnylam-pharmaceuticals.md)
Stage: Proto (2 of 5: Research → Proto → Pilot → Deploy → Scaling)
Updated: last update 2026-07-15, facts checked 2026-10-11
Goal: Stop amyloid at its source by switching off the gene that makes it, rather than clearing plaques after they form, first in cerebral amyloid angiopathy, where amyloid in brain vessels causes bleeds and dementia.
Status: Phase 2 in cerebral amyloid angiopathy fully enrolled (data 2028); Down syndrome Alzheimer's trial started.
Next milestone: cAPPricorn-1 placebo-controlled portion completes, target Aug 2027

## Milestones

| Status | Milestone | Date | Slip |
| --- | --- | --- | --- |
| Done | First-in-human phase 1 starts | Feb 2022 |   |
| Done | FDA lifts partial hold: multiple doses up to 180 mg every 6 months | Feb 2024 |   |
| Done | cAPPricorn-1 phase 2 in CAA starts | May 2024 |   |
| Done | cAPPricorn-1 enrollment complete; Down syndrome trial starts | Jul 2026 |   |
| Current | cAPPricorn-1 placebo-controlled portion completes | Aug 2027 |   |
| Planned | cAPPricorn-1 initial results | 2028 |   |

## Upcoming events

- **Aug 2027**: cAPPricorn-1 placebo-controlled portion completes
- **2028**: cAPPricorn-1 initial results

## Most important updates, last 3 months

- **15 Jul 2026**: Alnylam completes enrollment of phase 2 mivelsiran trial in cerebral amyloid angiopathy; starts Down syndrome study. At AAIC 2026, Alnylam said the cAPPricorn-1 phase 2 of mivelsiran in cerebral amyloid angiopathy is fully enrolled, with the rate of new brain microbleeds on MRI as the primary endpoint and first results expected in 2028. ([our story](https://technooptimist.io/stories/alnylam-completes-enrollment-of-phase-2-mivelsiran-trial-in-cerebral-1187016a.md) · [original source](https://www.biospace.com/press-releases/alnylam-highlights-progress-with-neuroscience-programs-at-aaic-2026-showcasing-potential-of-rnai-in-neurological-disease))

## Current obstacles

- **Does lowering APP help clinically?**: Biomarkers fall sharply, but no trial yet shows fewer brain bleeds or slower dementia; first test is 2028.
- **APP has normal jobs**: APP plays roles in neurons; an early animal-toxicology finding caused a partial FDA hold on high or frequent doses.

## Physics limits

- **The brain is hard to reach**: Blood-borne RNA can't cross the blood-brain barrier, so brain RNAi needs spinal injections, and distribution to deep brain regions is uneven.
- **Prevention needs long trials**: Amyloid builds over decades; showing that lowering its source prevents decline takes years and large trials.

## How it works

### Silence APP: Cut the message

A small interfering RNA guides the cell's own machinery to destroy APP messenger RNA, so less APP protein is made.

### C16 lipid tag: Reaches brain cells

A 16-carbon fatty tail helps the RNA spread through brain tissue and enter neurons, astrocytes and microglia.

### Upstream: Less raw material for amyloid

Less APP means less amyloid-beta to clump into plaques in tissue (Alzheimer's) and in vessel walls (CAA).

### Infrequent dosing: Months per injection

Gene silencing persists for months, allowing dosing as rarely as every six months.

## Spec sheet

| Spec | Mivelsiran (ALN-APP) | Provenance |
| --- | --- | --- |
| Max CSF sAPPβ reduction (top dose) | -89.9% | reported |
| Max CSF Aβ42 reduction (top dose) | -70.2% | reported |
| Brain swelling (ARIA-E) | None seen | reported |
| cAPPricorn-1 planned size | ~200 people with CAA | reported |
| Route | Injection into spinal fluid | reported |

Provenance: reported = stated by the company; estimated = our estimate; sample = a sample figure.

## About Alnylam Pharmaceuticals

Alnylam develops RNAi therapeutics that silence disease-causing genes. Amvuttra exceeded $1B quarterly revenue in Q2 2026.

- Alnylam commercialized RNAi technology, filing four approved medicines by 2023.
- Amvuttra hit $1.01B quarterly revenue in Q2 2026, up 106%, about 15 months after ATTR-CM launch.
- Pipeline includes next-gen nucresiran, mivelsiran (Alzheimer's), and programs for diabetes, obesity.

- Founded: 2002
- Headquarters: US
- Status: public
- Staff: ~2,500
- Website: https://www.alnylam.com
- People: Yvonne Greenstreet (Chief Executive Officer)
- Partners, customers, investors: Roche (partner); Regeneron (partner); Inceptive (partner)

Company page: https://technooptimist.io/companies/alnylam-pharmaceuticals.md

## Related programs

More from Alnylam Pharmaceuticals:

- [Amvuttra (vutrisiran)](https://technooptimist.io/biotech/amvuttra.md) (Deploy)
- [Nucresiran (ALN-TTRsc)](https://technooptimist.io/biotech/nucresiran.md) (Pilot)
- [Zilebesiran](https://technooptimist.io/biotech/zilebesiran.md) (Pilot)

Everything in Biotech: https://technooptimist.io/biotech.md

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