Glafabra Therapeutics — Fabry Disease: Clinical Data (FACTS Trial)
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Fabry Disease: Clinical Proof of Concept

FACTS Trial (NCT02800070) — 5-Year Phase 1 Results
Live-cel Autologous Lentiviral HSC Gene Therapy Platform · GT-GLA-S03

Trial: FACTS — NCT02800070 Patients: 5 treated / 5-year follow-up Key result: 48% lyso-Gb3 reduction (p < 0.0001) Safety: 0 product-attributable SAEs Sources: Khan et al., Nat Commun 2021 (PMC7907075) & Foley et al., Clin Transl Med 2025 (PMC11726700)
5
Patients treated
(5-year follow-up)
48%
Mean lyso-Gb3 reduction from no-ERT baseline
(p < 0.0001, 99% power)
0
Product-attributable serious adverse events across 5 years
3/5
Patients who qualified to discontinue ERT post-gene therapy
Framing Note. The FACTS trial was a Phase 1 investigator-initiated trial conducted by co-founders Drs. Medin and Foley under Canadian regulatory oversight. This is not Glafabra's own IND-cleared program. It establishes proof of concept for the Live-cel platform underlying GT-GLA-S03. Do not characterize Glafabra as "clinical-stage" — the correct framing is pre-IND, preclinical-stage, with co-founder Phase 1/2 proof of concept in hand.
1

Trial Registration & Design — FACTS (NCT02800070)

Registration & Design
NCTNCT02800070
Health Canada CTAApproved April 26, 2016
PhasePhase 1 (Safety pilot)
DesignMulti-center, single-arm, open-label
Screened / Treated7 screened → 5 treated (2 failed screening)
EnrollmentSeptember 2016 – October 2018
Follow-up5 years (End-of-Study February 2024)
SitesCalgary AB · Toronto (UHN/Princess Margaret) · Halifax NS
Safety gatingSequential enrolment; CTSC + DSMC review required before each successive patient authorized
Endpoints
Primary: Safety and toxicity — graded by NCI CTCAE v4.03 across cardiac, renal, and neurological (stroke) organ systems throughout 5-year follow-up.
Secondary:
  • Alpha-Gal A enzyme activity — plasma, peripheral blood leukocytes, and bone marrow
  • Lyso-Gb3 and Gb3 levels in plasma and urine
  • VCN persistence in peripheral blood (qPCR)
  • Anti-alpha-Gal A IgG antibody titres
Eligibility (key): Males 18–50; confirmed classical Fabry disease; on ERT ≥6 months; eGFR >45 mL/min/1.73m² (CKD-EPI); LVEF >45%; no advanced organ disease.
Source: Khan et al., Nat Commun 2021 (PMC7907075); ClinicalTrials.gov NCT02800070
Conditioning Regimen. Patients received non-myeloablative reduced-intensity conditioning with melphalan 100 mg/m² (100mel) administered outpatient. This distinguishes the Live-cel approach from myeloablative regimens used by other HSC gene therapy programs (e.g., AVROBIO). Patients 1, 4, and 5 were discharged same-day; Patient 3 never resumed ERT.
2

5 Patients Treated — Baseline & Drug Product Characteristics

All five patients were male with confirmed classical Fabry disease, on ERT prior to enrollment. VCN values reflect vector copies per cell genome measured in the drug product prior to infusion. CD34+ cell doses reflect the per-kg infused cell count.

Patient 1
Age48 Mutationp.Gln321Arg VCN (product)0.68 copies/genome CD34+ infused4.9 ×106/kg
Patient 2
Age39 Mutationp.Ser345Pro VCN (product)1.43 copies/genome CD34+ infused6.4 ×106/kg
Patient 3
Age39 Mutationp.Ala143Pro VCN (product)0.81 copies/genome CD34+ infused13.8 ×106/kg
Patient 4
Age37 Mutationp.Ala143Pro VCN (product)1.37 copies/genome CD34+ infused6.2 ×106/kg
Patient 5
Age29 Mutationp.Tyr134Ser VCN (product)1.13 copies/genome CD34+ infused3.1 ×106/kg
Mean drug product VCN: 1.08 copies/genome (range 0.68–1.43). All products manufactured using the LV-AGA self-inactivating lentiviral vector. Engraftment (neutrophil/platelet recovery) occurred Days 11–13 in all five patients. Alpha-Gal A enzyme first detected in plasma Days 6–8 post-infusion.
3

Safety Profile — 5 Years / 5 Patients

0
Product-attributable SAEs across 5 years
(2 Grade 1–2 product-related AEs only: nausea, cough)
5/5
Patients engrafted successfully
(neutrophil/platelet recovery Days 11–13)
3/5
Patients who qualified and elected to discontinue ERT post-gene therapy (Patient 3 never resumed)
4/5
Outpatient administration
(same-day discharge: Patients 1, 3, 4, 5)
Safety Category Finding at 18-Month Interim Finding at 5-Year End-of-Study
Product-attributable SAEs 0 (5/5 patients) 0 (5/5 patients)
Product-related AEs 2 Grade 1–2 events: nausea (P4), cough (P2) No new product-related AEs beyond 18 months
Cardiac (LVMI) Stable in all patients; no new LGE or T1 mapping changes Patients 1, 2, 3 transient LVMI increase then reduction by Year 5; no LGE change in any patient
Renal function (eGFR) Stable in all patients; Patient 2 progressive CKD (pre-existing Stage 3a) Patients 3–5 near 90+ mL/min/1.73m²; Patient 2 stabilized Year 3 (slope 0.11)
Genotoxicity / ISA Polyclonal integration profile; no clonal dominance at 18 months Polyclonal reconstitution confirmed at 5 years; no clonal dominance; VCN mirrors enzyme activity (R² > 0.80)
Anti-alpha-Gal A IgG Pre-existing antibodies declined in 3/4 affected patients without resurgence All antibody titres at or near baseline beyond 18 months; no sustained elevation in any patient at 5 years
Health economics N/A Estimated $4.8M CAD health system savings from ERT pause in 3 patients through last visit

Source: Khan et al., Nat Commun 2021 (PMC7907075); Foley et al., Clin Transl Med 2025 (PMC11726700)

4

Summary Charts — Engraftment, Substrate Reduction & Renal Function

Bone Marrow Alpha-Gal A Activity at Day 28 Post-Infusion (per patient)
Source: Khan et al., Nat Commun 2021 (PMC7907075). Values reflect engrafted gene-therapy-treated bone marrow cells measured 28 days after infusion. Fold increase labels reflect each patient's individual pre-treatment BM baseline (Day −2: range 0.3–1.6 nmol/hr/mg). Average increase across all 5 patients: ~444× over individual baseline (range 106×–733×). Red bar shows the mean pre-treatment Fabry baseline for reference.
Drug Product Vector Copy Number — Day 28 Post-Infusion (per patient)
Source: Khan et al., Nat Commun 2021 (PMC7907075). Mean VCN (red dashed line): 1.08 copies/genome. All values within the acceptable therapeutic window.
Plasma Lyso-Gb3 Trajectory vs. ERT (indexed to pre-treatment baseline)
Gene therapy line: Foley et al., Clin Transl Med 2025 (PMC11726700); Khan et al. 2021 (PMC7907075). ERT reference band (gold): Fabrazyme (agalsidase beta, 1 mg/kg q2w) typically achieves 40–68% plasma lyso-Gb3 reduction with continuous biweekly dosing. Critically, ERT levels rebound to baseline upon treatment discontinuation; the gene therapy effect shown reflects a single administration.
eGFR Slope Post-Gene Therapy (mL/min/1.73m² per year)
Source: Foley et al., Clin Transl Med 2025 (PMC11726700). Negative values indicate modest decline; all within or near therapeutic target of ≤3 mL/min/1.73m²/year. Note on P2: Patient 2 enrolled with pre-existing Stage 3a CKD (eGFR ~50 mL/min/1.73m²). Yr0–3 slope was −7.48; marked stabilization in Yr3–5 (slope 0.11) may reflect gene therapy-mediated disease modification.
5

Interim vs. 5-Year End-of-Study Outcomes

Endpoint Phase 1 Interim (18 months, 2021) 5-Year End-of-Study (2025)
Plasma lyso-Gb3 40–86% reduction from baseline within 3 months; reduced in most patients Significantly lower in 4/5 patients; stable from Years 1–5
Alpha-Gal A activity Detected Days 6–8 in all 5 patients; plasma reached reference range levels; leukocyte activity supranormal Stabilized above Fabry disease baseline in all patients; not returned to pre-treatment levels; Patient 5 supranormal throughout
Vector copy number Highest at 30–60 days; declining but durable (Patient 1: >0.05 copies/genome at ~3 years) Polyclonal; no clonal dominance at 5 years; VCN mirrors enzyme activity (R² > 0.80)
Renal function (eGFR) Stable in all patients; Patient 2 progressive CKD (pre-existing) Patients 3–5 near 90+ mL/min/1.73m²; Patient 2 stabilized Year 3 (slope 0.11); Patient 1 slope 0.09
Cardiac (LVMI) Stable in all patients; no new LGE or T1 mapping changes Patients 1, 2, 3 transient LVMI increase then reduction by Year 5; no LGE change in any patient
Product-attributable SAEs 0 (5/5 patients) 0 (5/5 patients, 5 years)
ERT discontinuation 3/5 patients qualified and elected to stop ERT; Patient 3 never resumed Estimated $4.8M CAD health system savings from ERT pause in 3 patients through last visit
Anti-alpha-Gal A antibodies Pre-existing antibodies declined in 3/4 affected patients without resurgence All antibody titres at or near baseline beyond 18 months; no sustained elevation in any patient at 5 years

Sources: Khan et al., Nat Commun 2021 (PMC7907075); Foley et al., Clin Transl Med 2025 (PMC11726700)

6

Longitudinal Biomarker Data — 5-Year Per-Patient Follow-up

Data from the Canadian FACTS trial, reported across two publications: Khan et al. 2021 (PMC7907075) covering the first 2–3 years of follow-up, and Foley et al. 2025 (PMC11726700) reporting the full 5-year end-of-study results. Where available, early timepoint values (Year 0 through approximately Year 2–2.7) are taken directly from machine-readable supplementary Excel tables published alongside Khan et al. 2021. For biomarkers where supplementary tabular data was not available, or for the Year 2–5 extension period covered only in the 2025 publication, values were digitized by visual inspection of the published figures in PMC11726700.

Each point represents a single measured value per patient. Year 0 = infusion date. Grey shaded bands indicate the published normal reference range for the relevant biomarker. Charts use a compressed x-axis beyond Year 2 to show early kinetics with precision while displaying the full 5-year window.

Fig. 1 — Plasma Alpha-Gal A Activity Over Time (5-Year). All five patients began below the normal reference range (grey band, 5.1–9.2 nmol/min/mL). Enzyme activity rose rapidly within weeks of infusion, reaching or exceeding the reference range in all patients by Month 3. Patient 5 (purple) remained at or above the upper reference range through Year 3.5. Patients 2–4 stabilized in the 2.8–4 nmol/min/mL range, detectably above the Fabry disease baseline, through Year 5. Early timepoint data (Year 0–2.7) from exact values in Khan et al. 2021 (PMC7907075); Year 3–5 extension digitized from Foley et al. 2025 Fig 2A (PMC11726700).

Fig. 2 — Leukocyte Alpha-Gal A Activity Over Time (5-Year). Leukocyte enzyme activity (nmol/hr/mg protein) provides a complementary engraftment readout to plasma activity. Grey dashed reference band marks the normal range (22–57 nmol/hr/mg protein). Patient 5 (purple) showed a dramatically elevated early response peaking at ~330 nmol/hr/mg protein at Month 6, then declining to ~40–60 nmol/hr/mg by Year 4–5, near the upper reference range. All data digitized from Foley et al. 2025 (PMC11726700, Fig. 2B, ±10 nmol/hr/mg protein precision).

Fig. 3 — Plasma Lyso-Gb3 Over Time (5-Year). Lyso-Gb3 (nM) is the primary pharmacodynamic endpoint planned for Glafabra's FDA trials. The dashed grey line marks the published reference range upper limit (~3 nM). All patients reduced from pre-treatment baseline by Month 3. Patient 5 (purple) is the standout result: starting at 16.6 nM, lyso-Gb3 dropped below 10 nM by Year 0.5 and remained 5–7 nM through all 5 years — approaching normal reference range. Patients 1 and 2 stabilized in the 14–19 nM range through Year 5 (>40% sustained reduction from no-ERT baseline). Early timepoint data from Khan et al. 2021 (PMC7907075); Year 1.5–5 extension digitized from Foley et al. 2025 Fig 3B (PMC11726700).

Fig. 4 — Vector Copy Number (VCN) in Peripheral Blood Over Time. VCN (copies/genome) reflects durable engraftment of gene-corrected HSCs. Exact values from Year 0–2 derive from supplementary data in Khan et al. 2021 (PMC7907075); Year 2–5 extension digitized from Foley et al. 2025 (PMC11726700, Fig. 4B). All patients show a peak engraftment phase at ~1–3 months post-infusion followed by stabilization at a durable plateau, consistent with polyclonal long-term repopulating HSCs. VCN correlated strongly with plasma enzyme activity (R² > 0.80).

Fig. 5 — eGFR Over Time (Years Post-Infusion). Early values (Year 0–2.7) from Khan et al. 2021 supplementary data; Year 1.5–5 extension digitized from Foley et al. 2025 (PMC11726700, Fig. 4A, ±2 mL precision). Patients 3, 4, and 5 maintained eGFR above 110 mL/min/1.73m² through 5 years. Patient 1 oscillated around 75–82 mL/min/1.73m² (stable CKD Stage 2). Patient 2 enrolled with pre-existing Stage 3a CKD and stabilized at ~25 mL/min/1.73m² from Year 3–5. Horizontal dashed line marks the CKD Stage 3a/3b threshold (60 mL/min/1.73m²).

Fig. 6 — IgG Antibody Titre Against Alpha-Gal A Over Time. All values digitized from Foley et al. 2025 (PMC11726700, Fig. 5A, ±15% precision on log scale). Y-axis is logarithmic. Patients 3 (gold) and 4 (red) mounted the highest early humoral responses (peak ~60,000 and ~30,000, respectively) then declined to baseline by Year 2–3. Patient 5 (purple) maintained near-background IgG levels throughout follow-up, consistent with the superior sustained enzyme activity observed. All antibody titres at or near background beyond 18 months in all patients.

Sources. Khan A et al. "Lentiviral Gene Therapy for Fabry Disease: Results from a Phase 1/2 Clinical Trial." Nat Commun 2021 (PMC7907075, PMID 33602921). — Foley S et al. "Five-Year Follow-Up of the FACTS Lentiviral Hematopoietic Stem Cell Gene Therapy Trial for Fabry Disease." Clin Transl Med 2025 (PMC11726700, PMID 39794302). — ClinicalTrials.gov NCT02800070.