WhelWomen's Health Evidence Lab
WHEL-C-053 · Emerging evidence · 4.5/10

Raloxifene for menopause

Per an Open Targets annotation, RALOXIFENE is a Phase 2 clinical candidate for menopause acting as an estrogen receptor beta modulator on estrogen receptor 2 (ESR2).

Origin · FDA ApprovedPathway · 505(b)(2) · existing active ingredient, new indicationEvidence arm · Pathway insightsEvidence supports
How to read thisThe summary above and the proposed mechanism are generated by the model from the sources it ingested, and are written as the model’s reasoning rather than established fact. Any figure quoted from MATRIX is a model-derived association score, not a clinical measurement. How far the published record backs this pair is carried by the score’s own rigor dimension and traced to verbatim sources at the foot of the page.

Hypothesized mechanism

RALOXIFENE modulates estrogen receptor beta (ESR2) signaling, potentially substituting for declining estrogen activity in menopause-related tissues.

This is the model’s proposed mechanism from the sources on file, not a demonstrated causal pathway. How well the published record supports it is reflected in the rigor and plausibility dimensions of the score, and traced to the verbatim sources at the foot of the page.

How the score was reached, for this pair

The composite score is the sum of five dimensions, each scored 0 to 2 by the model from the evidence on file. Below is the sub-score this specific pair received on each, with what that dimension measures. It scored 4.5 of 10 overall, a emerging reading, from a pathway rated emerging in strength.

The model’s overall reasoning for this pair is the summary at the top of the page, and the mechanism it proposed is in the section above.

Pathway arm · anchors the headline4.5 / 10 · Emerging

Scored for women. Female representation not stated — applicability to women uncertain (flagged for full text). (band F4, ×0.75).

Corroboration

Only a single line of evidence is present: one Open Targets database entry linking RALOXIFENE to estrogen receptor 2 (ESR2). No independent mechanistic lines converge to support the claim.

0 / 2

Rigor

The evidence is a curated database annotation (Open Targets) citing a Phase 2 clinical stage for menopause, which implies human-relevant context but provides no actual study data or model details. It is essentially a target-tractability annotation rather than experimental rigor.

1 / 2

Specificity

The claim specifies a defined molecular action: RALOXIFENE acts as an estrogen receptor beta modulator on the named target estrogen receptor 2 (ESR2). This is a specific drug-target interaction as stated.

2 / 2

Plausibility

Modulation of estrogen receptor beta (ESR2) is a highly plausible mechanism for a menopause-related phenotype given estrogen signaling's central role in menopausal physiology. The target-phenotype fit is strong as a SERM acting on an estrogen receptor.

2 / 2

Consistency

There is only one signal (a single database annotation), so there is no internal disagreement, but also no multiple signals to confirm directional consistency. Consistency cannot be meaningfully demonstrated with a single source.

1 / 2
How the scoring rubric works, in general

Regulatory & development status

Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for menopause (on-label) or approved for something else (off-label), whether the molecule is available as a generic or a single-source brand still under patent, and how far it has been studied as a therapy for this condition. Each fact is drawn from a public US source and reported beside the score; none of it is folded into the score.

This is descriptive context, not regulatory advice. It maps the landscape a 505(b)(2)route would build on (an already-approved active ingredient proposed for a new indication), but it is not a 505(b)(2) viability assessment, and says nothing about whether any particular development path is advisable. “Approved” means FDA-approved (US); approvals elsewhere are out of scope.

Approval relationship On-label (FDA-approved for this use)

Read from the drug’s FDA label via DailyMed, the US National Library of Medicine’s label repository. A label is only counted when it carries an FDA-approved marketing category (an NDA, ANDA, or biologic BLA); dietary supplements, homeopathics, and OTC-monograph products are not FDA-approved drugs and are excluded.

For this pair. This condition appears in the drug's FDA-approved label (Indications & Usage), so using it here is an approved, on-label use.

From the label’s Indications & Usage section: “strogen agonist/antagonist indicated for: Treatment and prevention of osteoporosis in postmenopausal women. (1.1) Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis., RALOXIFENE HYDROCHLORIDE TABLET, FILM COATED [AMNEAL PHARMACEUTICALS LLC] · view label ↗

Generic & patent supply Generic available

Read from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), using single-ingredient products only so that patents on novel branded combination formulations are never attributed to the base molecule.

For this molecule. A live ANDA lists this active ingredient, so the basic molecule is available as a generic (off-patent in its basic form).

EVISTA · NDA (brand) · 60MG · rx · approved Dec 9, 1997
RALOXIFENE HYDROCHLORIDE · ANDA (generic) · 60MG · rx · approved Apr 8, 2016
RALOXIFENE HYDROCHLORIDE · ANDA (generic) · 60MG · rx · approved Aug 28, 2015
RALOXIFENE HYDROCHLORIDE · ANDA (generic) · 60MG · rx · approved Aug 18, 2020
RALOXIFENE HYDROCHLORIDE · ANDA (generic) · 60MG · rx · approved Mar 22, 2016

Clinical-trial stage, for this condition Phase 3

Read from ClinicalTrials.gov (US National Library of Medicine). A trial only counts when the drug appears as an experimental or active-comparator intervention in an interventional study of this condition; mechanistic, drug-interaction, post-marketing (Phase 4), and comparator-background uses are excluded, so this reflects the drug being tested as a therapy for menopause.

For this pair. Studied in 4 qualifying interventional trials · highest stage reached Phase 3 · completed.

NCT00383422 · Phase 3 · completed
NCT01573637 · Phase 3 · completed
NCT00149604 · Phase 2 · completed
NCT00031811 · completed
The regulatory and trial sources this status is drawn from

Layers not covered for this pair

Sex-specific pharmacokineticsNone on file

Not covered for this pair. This layer holds documented sex-specific pharmacokinetics for a limited set of drugs, and this compound is not among them yet. A blank here means the drug is not covered by the layer, not that no sex difference exists.

More on the sex-specific pharmacokinetics layer and its sources
Cycle-phase dependenceNone on file

Not covered for this pair. The cycle-phase layer is seeded for the strongest-evidence cases so far (PMDD), and this pair is not among them yet. A blank here means the pair is not covered by the layer, not that the effect was found to be phase-independent.

More on the cycle-phase layer and its sources

Source evidence · what the pipeline ingested

These are the sources the pipeline ingested to detect and score this signal, the published literature the model actually read, each tagged by study type. Where the model combined findings the claim is marked as a synthesis (S), and where the literature disagrees the contradiction is shown (!).

Every source below belongs to this signal’s evidence arm, Pathway insights. Whel reads each drug-condition pair through four such arms, each held to its own inclusion bar; a signal is surfaced through one of them.

  • 1Per Open Targets (retrieved 2026-06-16), RALOXIFENE (a Small molecule) is a clinical candidate for menopause (maximum clinical stage PHASE_2); its mechanism of action is Estrogen receptor beta modulator on target estrogen receptor 2. Open Targets · mechanistic

These are the verbatim sources the pipeline surfaced and read; they may not be the full published record for a pair, and the score reflects the strength and agreement of the evidence rather than its volume. The strength of these source types is what the rigor dimension of the score reads off. MATRIX, sex-specific pharmacokinetics, and cycle phase are separate layers the pipeline does not ingest, external cross-references reported beside the score, and they link to their own sources in their sections above.

The primary sources and pipelines this evidence is drawn from