Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies

1. Is the biology right?

• Somatic driver evidence: no · None of IL3RA, IL3RA, EEF2, POLA1, POLD4, POLD3, NR3C1 has somatic-mutation evidence in childhood acute lymphoblastic leukemia

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: IL3RA in childhood acute lymphoblastic leukemia, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for IL3RA, IL3RA, EEF2, POLA1, POLD4, POLD3, NR3C1 in childhood acute lymphoblastic leukemia

  Rule: Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence. Source: Open Targets: IL3RA in childhood acute lymphoblastic leukemia, 2026-11-11
• Pediatric target: yes · IL3RA, IL3RA on the FDA list

  Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study. Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
• Haematologic cancer: yes · Haematologic

  Rule: From the indication, or the registry conditions when no indication matches. Source: ClinicalTrials.gov NCT05476770, 2026-11-11

  Published context: Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid (BIO / Informa / QLS 2021, 2011–2020). Population-level, not a prediction.

• Background therapy: Fludarabine, Cytarabine, Vincristine, Azacitidine, Methotrexate: standard agents, not counted in these flags.
• IL3RA (via Tagraxofusp): Open Targets has no association between IL3RA and childhood acute lymphoblastic leukemia. · Open Targets: IL3RA in childhood acute lymphoblastic leukemia
• IL3RA (via Tagraxofusp): Open Targets has no association between IL3RA and childhood acute lymphoblastic leukemia. · Open Targets: IL3RA in childhood acute lymphoblastic leukemia
• EEF2 (via Tagraxofusp): Open Targets has no association between EEF2 and childhood acute lymphoblastic leukemia. · Open Targets: EEF2 in childhood acute lymphoblastic leukemia
• POLA1 (via Cytarabine IT): Open Targets has no association between POLA1 and childhood acute lymphoblastic leukemia. · Open Targets: POLA1 in childhood acute lymphoblastic leukemia
• POLD4 (via Cytarabine IT): Open Targets has no association between POLD4 and childhood acute lymphoblastic leukemia. · Open Targets: POLD4 in childhood acute lymphoblastic leukemia
• POLD3 (via Cytarabine IT): Open Targets has no association between POLD3 and childhood acute lymphoblastic leukemia. · Open Targets: POLD3 in childhood acute lymphoblastic leukemia
• NR3C1 (via Hydrocortisone): Open Targets has no association between NR3C1 and childhood acute lymphoblastic leukemia. · Open Targets: NR3C1 in childhood acute lymphoblastic leukemia

• Not loaded on this app yet: Normal-tissue expression in vital organs. Source: Human Protein Atlas (ticket 36).
• Not loaded on this app yet: Pan-essential in cell lines. Source: DepMap (ticket 36).
• Not loaded on this app yet: Approved drug on this target. Source: Drugs@FDA (ticket 30).

2. Can the result be trusted?

• Randomised: no · Non-randomised

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT05476770, 2026-11-11
• Small denominator: no · 54 planned; each patient moves a rate by 100 ÷ 54 = 1.9 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT05476770, 2026-11-11
• Primary endpoint is overall survival: no · Occurrence of dose limiting toxicity (DLT) during cycle 1 of therapy

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT05476770, 2026-11-11

  Published context: Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3 (Otsuka 2021, 400 phase 3 oncology trials, to 2020). Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival.

  Published context: 52% of surrogate-to-OS correlations are low (Prasad 2015, published to 2014). Shown with the figure above.
• Results overdue: no · Primary completion expected 2025-11-11; not yet due

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT05476770, 2026-11-11

• Not loaded on this app yet: Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff. Source: Readout extraction (ticket 32).
• Not loaded on this app yet: Primary endpoint changed between registry versions. Source: Registry versions in the store (ticket 32).

3. What must it beat?

• Not loaded on this app yet: Control-arm result and approved therapies for the same segment, with label links. Source: Drugs@FDA, FDA labels and readouts (tickets 30, 32).

4. Too crowded, or too late?

• Stopped on this target: 11 terminated, withdrawn or suspended trials of drugs against IL3RA; 2 give no reason. Reasons are quoted as the registry gives them on the target page. · IL3RA: what already stopped

• Not loaded on this app yet: Programs on the target by phase and months behind the leader. Source: Programs and Drugs@FDA (ticket 33).

5. Can it be approved, and stay approved?

• Single-country: no · 31 sites in 2 countries; 29 in the United States (94%)

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT05476770, 2026-11-11
• EU paediatric investigation plan: yes · EMEA-002305-PIP01-17-M01 (hydrocortisone (hemisuccinate), Prevention of bronchopulmonary dysplasia): PM: decision on the application for modification of an agreed PIP, 9 Sept 2020; compliance positive 23 Feb 2024; EMEA-002739-PIP01-19 (hydrocortisone;benzocaine, Treatment of haemorrhoidal disease): W: decision granting a waiver in all age groups for all conditions or indications, 13 May 2020; EMEA-001283-PIP01-12 (hydrocortisone, Treatment of adrenocortical insufficiency): W: decision granting a waiver in all age groups for all conditions or indications, 26 Feb 2013; compliance positive 14 Oct 2016; EMEA-000277-PIP01-08 (calcipotriol hydrate;hydrocortisone, Psoriasis vulgaris): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 20 Apr 2009; +1 more

  Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
• EU orphan designation: yes · EU/3/07/441 withdrawn 20 Mar 2007: Treatment of adrenal insufficiency; EU/3/06/372 expired 22 May 2006: Treatment of adrenal insufficiency; EU/3/05/296 positive 27 Jul 2005: Treatment of congenital adrenal hyperplasia; EU/3/15/1567 positive 11 Nov 2015: Treatment of blastic plasmacytoid dendritic cell neoplasm

  Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
• Authorised in the EU: yes · Alkindi: authorised since 9 Feb 2018; Efmody: authorised since 27 May 2021; Hydrocortisone Aguettant: application withdrawn; Elzonris: authorised since 7 Jan 2021, orphan medicine, exceptional circumstances; +1 more

  Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
• FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link

  Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
• FDA pediatric oncology approval: yes · Tagraxofusp-erzs [Elzonris], 21 Dec 2018: Treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

  Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
• Registered studies open to children: yes · 358 interventional studies of Tagraxofusp, Cytarabine IT, Hydrocortisone include patients under 18; 82 are recruiting, not yet recruiting or active

  Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11

• Caveat: Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality.
• Rare pediatric disease voucher: FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. · FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

• Not loaded on this app yet: Precedent approvals for target, modality and endpoint; accelerated-approval status. Source: Drugs@FDA and FDA accelerated-approval tables (ticket 30).

6. Can the sponsor finish?

• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium (academic or other) · ClinicalTrials.gov NCT05476770
• study chair: Adam Lamble, MD, Seattle Children's Hospital · Person page

• Not loaded on this app yet: Filed cash, quarterly spend and the runway arithmetic. Source: SEC XBRL company facts (ticket 37).
• Not loaded on this app yet: Sponsor's completed vs stopped oncology trials and results-reporting record. Source: Registry, by company (ticket 37).

What public data cannot tell you

Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.