Drug Update · Rare Disease

FDA Approves marnetegragene autotemcel for LAD-I: 100% HSCT-free

July 25, 2026

Approval date

03/26/2026

Indication

treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available HLA-matched sibling donor for allogeneic hematopoietic stem cell transplant

Primary result

HSCT-free survival 100% at 1 year (95% CI, 66 to 100; P<0.001)

Median CD18 expression at Month 12

54%

Median CD11a expression at Month 12

45%

Recommended minimum dose

2.8 × 10^6 CD34+ cells/kg

Clinical Perspective

Pediatric hematologists and transplant teams caring for children with molecularly confirmed severe LAD‑I now have an FDA‑approved autologous gene therapy option for patients without an available HLA‑matched sibling donor, per the labeled indication ^[5]^[4]. The approval is based on a surrogate biomarker increase in neutrophil CD18 and CD11a expression at Month 12 with sustained expression through Month 24; continued approval may be contingent on verification of clinical benefit in post‑marketing confirmatory trials ^[5]^[6]. How centers will integrate complex manufacturing, myeloablative conditioning, and long‑term LVV surveillance into existing care pathways for these children will require coordination between specialty centers, and what confirmatory clinical outcomes will be reported in ongoing follow‑up remains to be seen?

Editorial Team · Rare Disease

The U.S. Food and Drug Administration approved Kresladi (marnetegragene autotemcel) on March 26, 2026, for the treatment of pediatric patients with severe leukocyte adhesion deficiency‑I (LAD‑I) due to biallelic variants in ITGB2 without an available HLA‑matched sibling donor for allogeneic hematopoietic stem cell transplant ^[5]^[4]. Approval was granted under the accelerated approval pathway based on increases in neutrophil CD18 and CD11a surface expression at Month 12 with sustained effect through Month 24 in a single‑arm, multicenter study; the phase 1–2 study also reported HSCT‑free survival of 100% at 1 year after infusion ^[6]^[1].

Clinical Context

Marnetegragene autotemcel (Kresladi) is an autologous hematopoietic stem cell–based gene therapy in which patients' CD34+ hematopoietic stem cells are transduced with a self‑inactivating lentiviral vector containing a functional ITGB2 transgene to restore CD18 expression and formation of the CD18/CD11a heterodimer (LFA‑1) on leukocytes ^[6]^[1]. The product is manufactured from mobilized, apheresis‑collected CD34+ cells and administered as a single intravenous infusion after myeloablative conditioning ^[4]^[6]. Rocket Pharmaceuticals, Inc. is the sponsor and manufacturer identified in the prescribing information and regulatory filings ^[3]^[2]. Allogeneic HSCT is a recognized curative approach for LAD‑I but is limited by donor availability and risks of graft‑versus‑host disease and graft failure, issues cited as rationale for developing autologous gene therapy ^[1].

Key Findings

The phase 1–2, open‑label, multinational trial reported HSCT‑free survival of 100% (95% confidence interval [CI], 66 to 100) at 1 year after infusion (P<0.001) among treated children with severe LAD‑I ^[1].
Neutrophil CD18 surface expression increased in all seven evaluable patients who had baseline CD18 <2%, with median CD18 surface expression at Month 12 of 54% (range: 20% to 87%) and at Month 24 of 50% (range: 16% to 82%); CD18 expression was sustained through at least Month 42 post‑infusion in those patients ^[6].
Neutrophil CD11a surface expression increased in all 9 patients, with median CD11a surface expression at Month 12 of 45% (range: 18% to 75%) and at Month 24 of 39% (range: 17% to 65%), sustained through at least Month 42 ^[6].
Clinical event measures reported in the trial showed reductions in infection burden: the annualized incidence of infection‑related hospitalizations beyond 90 days after engraftment through 24 months was 74.45% lower than before infusion; annualized incidence of prolonged infection‑related hospitalizations was 81.95% lower; and annualized incidence of prespecified serious infections was 84.90% lower ^[1].

Safety & Tolerability

Serious adverse events related to myeloablative busulfan conditioning were observed in the trial; no adverse events were attributed to the gene therapy product itself in the reported study ^[1].
The prescribing information and label identify the most common non‑laboratory adverse reactions (≥ 30%) as mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection ^[4].
The most common laboratory adverse reactions (≥ 30%) listed in the label are hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, aspartate aminotransferase increased, and alanine aminotransferase increased ^[4].
Warnings and precautions in labeling include serious infections, veno‑occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, lentiviral vector (LVV)‑mediated insertional oncogenesis (lifelong risk of hematologic malignancy with recommended monitoring for at least 15 years), and hypersensitivity reactions including anaphylaxis ^[4].

Study Design

The pivotal evidence comprises a phase 1–2, multinational, open‑label study that enrolled nine pediatric patients with severe LAD‑I and followed them for up to 24 months in the primary report, with longer median follow‑up reported in regulatory documents; the study evaluated autologous CD34+ HSCs transduced with a lentiviral vector encoding ITGB2 ^[1]^[6]. The clinical program included RP‑L201‑0318 (ClinicalTrials.gov NCT03812263) and reported surrogate endpoints of neutrophil CD18 and CD11a surface expression at Month 12 and sustained through Month 24, plus clinical event reductions; trial details and long‑term follow‑up data appear in the published report and prescribing information ^[1]^[6].

FAQ

What is Kresladi (marnetegragene autotemcel) approved for?

Kresladi is indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency‑I (LAD‑I) due to biallelic variants in ITGB2 who do not have an available human leukocyte antigen (HLA)‑matched sibling donor for allogeneic hematopoietic stem cell transplant. This approval was granted under the accelerated approval pathway based on increases in neutrophil CD18 and CD11a surface expression.

How does marnetegragene autotemcel work?

Kresladi is an autologous hematopoietic stem cell‑based gene therapy in which patients' CD34+ cells are transduced ex vivo with a self‑inactivating lentiviral vector carrying a functional ITGB2 transgene. After infusion following conditioning, transduced HSCs engraft and differentiate into leukocytes that express functional CD18, enabling formation of the CD18/CD11a heterodimer (LFA‑1) important for leukocyte adhesion and extravasation.

What is the recommended dose and administration approach?

Kresladi is given as a single intravenous infusion. The prescribing information states the recommended minimum dose is a single intravenous infusion of 2.8 × 10^6 CD34+ cells/kg, with dose calculated based on the patient's weight prior to first apheresis; product manufacture requires mobilization with G‑CSF and plerixafor and apheresis to obtain CD34+ cells, and full myeloablative conditioning must be administered before infusion.

What are the most common side effects and key safety considerations?

The label lists the most common non‑laboratory adverse reactions (≥ 30%) as mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection, and the most common laboratory adverse reactions (≥ 30%) include decreases in hemoglobin, platelet count, neutrophil count, leukocyte count, and increases in AST and ALT. Warnings include serious infections, veno‑occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, LVV‑mediated insertional oncogenesis with recommended long‑term monitoring, and hypersensitivity reactions.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves marnetegragene autotemcel for LAD-I: 100% HSCT-free

FDA Approves marnetegragene autotemcel for LAD-I: 100% HSCT-free

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Rare Disease in your inbox.

Related Clinical Updates

FDA Approves Elamipretide for Barth Syndrome: 63 N Knee Strength Gain

FDA Approves KYGEVVI for TK2d: Cuts Death Risk 86%

DTX401 Achieved 68% Cornstarch Reduction in Adults With GSDIa

Verified HCP Portal