Dihexa acetate: how it got to PCAC

Origin

Dihexa is an angiotensin IV-derived hexapeptide analogue, also written N-hexanoic-Tyr-Ile-(6) aminohexanoic amide. The 2015 review by Wright and Harding in the Journal of Alzheimer’s Disease described the molecule as a research compound developed in their laboratory at Washington State University, designed as an orally available, blood-brain-barrier-penetrant angiotensin-IV-based small molecule that engages the hepatocyte growth factor (HGF) / c-Met receptor system PMID 25649658. In bulk-drug nomenclature, the substance is sometimes nominated as “Dihexa acetate” — the acetate counter-ion form most commonly distributed.

Research history

Dihexa has a sparse peer-reviewed footprint as of May 2026. A PubMed search for the molecule returns a small number of indexed records, the majority of them authored by the originating Washington State University group or close collaborators, and one of which was retracted. The cited Wright and Harding review summarized animal-model findings: the authors reported that Dihexa was orally active, penetrated the blood-brain barrier, and produced effects on memory consolidation and dendritic spine density in rodent and in-vitro assays. The same review concluded only that

This angiotensin-based small molecule may be efficacious as a treatment for AD.

A 2018 systematic review by Ho and Nation at the University of Southern California in Neuroscience and Biobehavioral Reviews surveyed the broader angiotensin-IV literature, including Dihexa, and observed that the cited cognitive findings derive from rodent and in-vitro work rather than from controlled human trials PMID 29733881. No registered ClinicalTrials.gov study uses Dihexa itself as the active pharmaceutical ingredient. A separate small molecule, ATH-1017 / fosgonimeton, developed by Athira Pharma in the same chemical lineage, has been the subject of registered clinical investigation; the ClinicalTrials.gov search index for that program is provided in the sources list as a related-program reference rather than as evidence about Dihexa proper (ClinicalTrials.gov ATH-1017 search).

Regulatory journey

Dihexa has no FDA-approved drug application and no EMA, TGA, or Health Canada marketing authorization indexed in the cited sources. Under the section 503A framework, FDA reviews bulk drug substance nominations and assigns them to one of three interim categories — Category 1 (eligible pending rulemaking), Category 2 (significant safety concerns, not eligible pending further evaluation), or Category 3 (insufficient information) (FDA — Bulk Drug Substances Used in Compounding).

A range of peptide bulk-drug nominations, including Dihexa-related substances, were placed in Category 2 pending advisory-committee review under FDA’s “may present significant safety risks” notice (FDA Category 2 notice). FDA scheduled Dihexa for the Pharmacy Compounding Advisory Committee meeting at the end of February 2027. PCAC will analyze the agency’s nomination review and recommend whether to add the substance to the 503A bulks list.

What’s at stake

The thinness of the indexed Dihexa literature is itself a regulatory data point. PCAC has previously recommended against inclusion of bulk substances where peer-reviewed human-efficacy and human-safety data are limited and where the published record is dominated by a single laboratory. The February 2027 briefing materials are expected to be the most consolidated public regulatory analysis of Dihexa to date; this page will be updated when they are released, and any indexed registered human trial of Dihexa itself will be added if one appears.