{
 "decision": {
  "id": "leqembi-2023-aa",
  "title": "Leqembi, accelerated approval",
  "outcome": "approved",
  "pathway": "Accelerated approval",
  "case": "BUILT",
  "action_date": "2023-01-06",
  "incomplete": false
 },
 "package": "lecanemab_bla761269",
 "documents": [
  {
   "code": "ltr",
   "title": "Approval letter",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf",
   "pages": 11,
   "sha256": "9cfca3470c37fdc3df0f53aa82a400eb38a03398e906ccbd2e58ff7364c7e22a",
   "cited": true
  },
  {
   "code": "SumR",
   "title": "Summary review",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf",
   "pages": 54,
   "sha256": "13564c498fc6766683075d19174a80d9abf08ec136399b00f5f4a3671cf649e5",
   "cited": true
  },
  {
   "code": "lbl",
   "title": "Prescribing information (label)",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s000lbl.pdf",
   "pages": 17,
   "sha256": "e1b801ebe601a22e1e52e2c5b8b0f257b64e9ec4620b18e7c5f183b83b138b51",
   "cited": true
  },
  {
   "code": "MedR",
   "title": "Clinical review",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761269Orig1s000MedR.pdf",
   "pages": 290,
   "sha256": "636fadc1dd6f59e63175616b2f4a4b2b3d82e59a60fed2a834e5cf643daab0e4",
   "cited": false
  },
  {
   "code": "StatR",
   "title": "Statistical review",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761269Orig1s000StatR.pdf",
   "pages": 49,
   "sha256": "3801dd3db1689129c1c7ef94c60a7ee964780cc12a98dc712eee66fd8f86d1e5",
   "cited": false
  }
 ],
 "missing_documents": [],
 "facts": {
  "action_date": {
   "doc": "ltr",
   "page": 11,
   "excerpt": "on behalf of WILLIAM H Dunn 01/06/2023",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=11",
   "value": "2023-01-06"
  },
  "sponsor": {
   "doc": "ltr",
   "page": 1,
   "excerpt": "Eisai Inc.",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=1",
   "value": "Eisai Inc."
  },
  "basis": {
   "quote": "This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI [see Clinical Studies (14)].",
   "doc": "lbl",
   "page": 2,
   "sid": "lbl:p2:s7",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s000lbl.pdf#page=2",
   "label": "Reduction in amyloid beta plaques"
  },
  "committee": {
   "quote": "Your application for Leqembi was not referred to an FDA advisory committee because this biologic did not raise new or unexpected safety or efficacy issues for a drug of this class.",
   "doc": "ltr",
   "page": 3,
   "sid": "ltr:p3:s11",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=3",
   "referred": false
  },
  "confirmatory": {
   "quote": "In order to verify the clinical benefit of lecanemab-irmb, conduct a randomized, controlled trial to evaluate the efficacy of lecanemab-irmb compared to an appropriate control for the treatment of Alzheimer’s disease.",
   "doc": "ltr",
   "page": 3,
   "sid": "ltr:p3:s19",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=3",
   "label": "PMR 4384-1: randomized, controlled trial",
   "completion": {
    "doc": "ltr",
    "page": 3,
    "excerpt": "Trial Completion: 09/2022",
    "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=3",
    "value": "09/2022"
   }
  }
 },
 "sponsor_ask": {
  "quote": "The applicant is seeking accelerated approval based on reduction in amyloid plaque burden measured by positron emission tomography (PET) imaging which is proposed to be reasonably likely to predict clinical benefit.",
  "doc": "SumR",
  "page": 3,
  "sid": "SumR:p3:s16",
  "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=3"
 },
 "positions": [
  {
   "quote": "The Agency has previously found with the accelerated approval of aducanumab that reduction of brain Aβ plaque on PET is reasonably likely to predict clinical benefit in Alzheimer’s disease.",
   "doc": "SumR",
   "page": 4,
   "sid": "SumR:p4:s7",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=4",
   "id": "LEQ-T1-1",
   "thread": "T1",
   "status": "Consistent",
   "compares_to": "ADU-T1-1",
   "status_review": "reviewed"
  },
  {
   "quote": "There is substantial evidence that lecanemab reduces Aβ plaques, and this reduction is reasonably likely to result in clinical benefit for patients.",
   "doc": "SumR",
   "page": 5,
   "sid": "SumR:p5:s5",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=5",
   "id": "LEQ-T1-2",
   "thread": "T1",
   "status": "Consistent",
   "compares_to": "ADU-T1-2",
   "status_review": "reviewed"
  },
  {
   "quote": "Prespecified analyses of data at Week 79 suggested reduced decline on clinical endpoints by approximately 20% to 40%, as well as a reduced decline on other clinically meaningful outcome measures.",
   "doc": "SumR",
   "page": 28,
   "sid": "SumR:p28:s14",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=28",
   "id": "LEQ-T2-1",
   "thread": "T2",
   "status": "Conditional",
   "compares_to": "ADU-T2-1",
   "status_review": "reviewed"
  },
  {
   "quote": "Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers.",
   "doc": "lbl",
   "page": 1,
   "sid": "lbl:p1:s48",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s000lbl.pdf#page=1",
   "id": "LEQ-T3-1",
   "thread": "T3",
   "status": "Consistent",
   "compares_to": "ADU-T3-1",
   "status_review": "reviewed"
  },
  {
   "quote": "Obtain an MRI prior to the 5th, 7th, and 14th infusions.",
   "doc": "lbl",
   "page": 2,
   "sid": "lbl:p2:s24",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s000lbl.pdf#page=2",
   "id": "LEQ-T3-2",
   "thread": "T3",
   "status": "Consistent",
   "compares_to": "ADU-T3-2",
   "status_review": "reviewed"
  },
  {
   "quote": "Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate treatment with LEQEMBI.",
   "doc": "lbl",
   "page": 5,
   "sid": "lbl:p5:s28",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s000lbl.pdf#page=5",
   "id": "LEQ-T3-3",
   "thread": "T3",
   "status": "Departs",
   "compares_to": "ADU-T3-1",
   "status_review": "reviewed"
  },
  {
   "quote": "Given the robust, persuasive, and consistent effects of lecanemab on an acceptable surrogate endpoint, brain Aβ plaque on PET, Study 201 can be considered a single adequate and well-controlled trial that provides substantial evidence of effectiveness.",
   "doc": "SumR",
   "page": 5,
   "sid": "SumR:p5:s1",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=5",
   "id": "LEQ-T4-1",
   "thread": "T4",
   "status": "Consistent",
   "compares_to": "ADU-T4-2",
   "status_review": "reviewed"
  },
  {
   "quote": "Although the 6- month exposure numbers did not meet the ICH E1 guideline, the Division considers that the number of 1 year exposures and the determination that Alzheimer’s disease is a serious and life-threatening disease offset those limitations.",
   "doc": "SumR",
   "page": 5,
   "sid": "SumR:p5:s11",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2023/761269Orig1s000SumR.pdf#page=5",
   "id": "LEQ-T4-2",
   "thread": "T4",
   "status": "Conditional",
   "compares_to": "ADU-T4-3",
   "status_review": "reviewed"
  },
  {
   "quote": "In order to verify the clinical benefit of lecanemab-irmb, conduct a randomized, controlled trial to evaluate the efficacy of lecanemab-irmb compared to an appropriate control for the treatment of Alzheimer’s disease.",
   "doc": "ltr",
   "page": 3,
   "sid": "ltr:p3:s19",
   "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761269Orig1s000ltr.pdf#page=3",
   "id": "LEQ-T5-1",
   "thread": "T5",
   "status": "Consistent",
   "compares_to": "ADU-T5-1",
   "status_review": "reviewed"
  }
 ],
 "edges": [
  {
   "from": "LEQ-T1-1",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T1-1",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T1"
  },
  {
   "from": "LEQ-T1-2",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T1-2",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T1"
  },
  {
   "from": "LEQ-T2-1",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T2-1",
   "to_decision": "aduhelm-2021-aa",
   "status": "Conditional",
   "thread": "T2"
  },
  {
   "from": "LEQ-T3-1",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T3-1",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T3"
  },
  {
   "from": "LEQ-T3-2",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T3-2",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T3"
  },
  {
   "from": "LEQ-T3-3",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T3-1",
   "to_decision": "aduhelm-2021-aa",
   "status": "Departs",
   "thread": "T3"
  },
  {
   "from": "LEQ-T4-1",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T4-2",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T4"
  },
  {
   "from": "LEQ-T4-2",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T4-3",
   "to_decision": "aduhelm-2021-aa",
   "status": "Conditional",
   "thread": "T4"
  },
  {
   "from": "LEQ-T5-1",
   "from_decision": "leqembi-2023-aa",
   "to": "ADU-T5-1",
   "to_decision": "aduhelm-2021-aa",
   "status": "Consistent",
   "thread": "T5"
  },
  {
   "from": "LQT-T1-1",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T1-1",
   "to_decision": "leqembi-2023-aa",
   "status": "Consistent",
   "thread": "T1"
  },
  {
   "from": "LQT-T2-1",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T2-1",
   "to_decision": "leqembi-2023-aa",
   "status": "Consistent",
   "thread": "T2"
  },
  {
   "from": "LQT-T3-1",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T3-1",
   "to_decision": "leqembi-2023-aa",
   "status": "Consistent",
   "thread": "T3"
  },
  {
   "from": "LQT-T3-2",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T3-3",
   "to_decision": "leqembi-2023-aa",
   "status": "Departs",
   "thread": "T3"
  },
  {
   "from": "LQT-T4-1",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T4-1",
   "to_decision": "leqembi-2023-aa",
   "status": "Consistent",
   "thread": "T4"
  },
  {
   "from": "LQT-T5-1",
   "from_decision": "leqembi-2023-traditional",
   "to": "LEQ-T5-1",
   "to_decision": "leqembi-2023-aa",
   "status": "Consistent",
   "thread": "T5"
  }
 ]
}