{
  "schema_version": "orion-curated-historical-brief-v1",
  "brief_id": "alny-amvuttra-2025-03-20",
  "brief_version": "1.0.0",
  "ticker": "ALNY",
  "company": "Alnylam Pharmaceuticals",
  "event_date": "2025-03-20",
  "event_time": null,
  "detected_at": null,
  "prepared_date": "2026-09-09",
  "historical_evidence_cutoff_date": "2025-03-20",
  "historical_coverage_note": "A retrospective comparison of selected dated documents, not proof that ORION collected them on the event date. Later registry material is separated.",
  "authorship": "Manually curated with AI assistance; checked against linked primary sources. Not a live or automatically generated product result.",
  "quality_flags": [
    "SELECTED_SOURCE_REVIEW",
    "HISTORICAL_EXAMPLE",
    "NO_EVENT_DAY_CAPTURE",
    "SOURCE_POPULATION_DIFFERENCE",
    "LATER_REGISTRY_CONTEXT"
  ],
  "sources": [
    {
      "id": "S1",
      "title": "FDA: AMVUTTRA original prescribing information",
      "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215515s000lbl.pdf",
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      "section": "Indications and usage; revised 6/2022",
      "file": "fda-amvuttra-label-2022-s000.pdf",
      "role": "historical_baseline",
      "retrieved_date": "2026-09-09",
      "retrieval_date_precision": "day",
      "published_at": null,
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      "timestamp_note": "No exact publication/retrieval time is asserted. File mtime is not a source publication timestamp.",
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      "raw_preserved": true
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    {
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      "title": "FDA: AMVUTTRA prescribing information, supplement 006",
      "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215515s006lbl.pdf",
      "source_type": "regulator_label",
      "published_date": "2025-03",
      "date_precision": "month",
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      "file": "fda-amvuttra-label-2025-s006.pdf",
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      "id": "S3",
      "title": "Alnylam: FDA approval announcement",
      "url": "https://investors.alnylam.com/press-release?id=28831",
      "source_type": "issuer_announcement",
      "published_date": "2025-03-20",
      "date_precision": "day",
      "section": "Dated company announcement; no publication time established",
      "file": "alnylam-approval-release-2025-03-20.html",
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      "retrieved_date": "2026-09-09",
      "retrieval_date_precision": "day",
      "published_at": null,
      "retrieved_at": null,
      "timestamp_note": "No exact publication/retrieval time is asserted. File mtime is not a source publication timestamp.",
      "raw_sha256": "3f4c22a5452dae695f549bb7d4b8907beb24b3a8265ebaf95679077d19dcdc2c",
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    {
      "id": "S4",
      "title": "Fontana et al.: HELIOS-B original trial paper (PubMed abstract)",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39213194/",
      "source_type": "original_trial_publication_abstract",
      "published_date": "2024-08-30",
      "date_precision": "day",
      "section": "Online publication 30 August 2024; journal issue 2 January 2025; DOI 10.1056/NEJMoa2409134; full publisher page unavailable to retrieval tool",
      "file": null,
      "role": "historical_publication_crosscheck",
      "retrieved_date": "2026-09-09",
      "retrieval_date_precision": "day",
      "published_at": null,
      "retrieved_at": null,
      "timestamp_note": "No exact publication/retrieval time is asserted. File mtime is not a source publication timestamp.",
      "raw_sha256": null,
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    },
    {
      "id": "S5",
      "title": "ClinicalTrials.gov: HELIOS-B, NCT04153149",
      "url": "https://clinicaltrials.gov/study/NCT04153149",
      "source_type": "sponsor_submitted_trial_registry",
      "published_date": "2026-01-12",
      "date_precision": "day",
      "section": "Current record last update posted 12 January 2026; results first posted 21 October 2025",
      "file": "ctg-NCT04153149-retrieved-2026-09-09.json",
      "role": "later_record_context_only_not_event_day_evidence",
      "retrieved_date": "2026-09-09",
      "retrieval_date_precision": "day",
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      "timestamp_note": "No exact publication/retrieval time is asserted. File mtime is not a source publication timestamp.",
      "raw_sha256": "b3dedf0752c05f22b262ac3e49d413f6fe421aefed3d24a46fa24436d49d8e69",
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  "clinical_result": {
    "source_id": "S2",
    "table": "14.2 / Table 4",
    "population": "overall population in March 2025 FDA label",
    "n": 654,
    "treatment_n": 326,
    "placebo_n": 328,
    "endpoint": "all-cause mortality and recurrent cardiovascular events",
    "hazard_ratio": 0.72,
    "confidence_interval_95": [
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      0.93
    ],
    "p_value": 0.01,
    "followup": "33 to 36 months",
    "estimation_method": "modified Andersen-Gill model, as reported by FDA; no re-estimation",
    "calculation": null
  },
  "excluded_claims": [
    "stock_return",
    "price_target",
    "investment_recommendation",
    "current_company_outlook",
    "automated_detection_latency",
    "medical_treatment_recommendation"
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}