First FDA-Approved Gene Therapy for Severe Leukocyte Adhesion Deficiency

KRESLADI (marnetegragene autotemcel) is an autologous hematopoietic stem cell-based gene therapy given as a one-time intravenous infusion. On the US Package Insert it is indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant.

This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression. Continued approval may depend on verification and description of clinical benefit in confirmatory trial(s).

Distinct path — not this carton (fact-only): Allogeneic hematopoietic stem cell transplant from a matched sibling (or other donor pathways under separate institutional practice) is not this autologous gene-therapy carton. Other primary immunodeficiencies are not this labelled ITGB2 severe LAD-I population. Today’s US labelled autologous gene-therapy door for severe pediatric LAD-I without a matched sibling donor is Rocket Pharmaceuticals KRESLADI STN 125806.

The FDA approved STN BLA 125806/0 on 26 March 2026 under accelerated approval. Approval letter issues U.S. License Number 2328 to Rocket Pharmaceuticals, Inc., Cranbury, NJ. Letter attention: Sanchali Kasbekar, PharmD. Associated NCT number on the letter: NCT03812263. Rare Pediatric Disease Priority Review Voucher noted on the FDA press announcement and company materials. Package Insert revised 3/2026. Manufactured for Rocket Pharmaceuticals, 9 Cedarbrook Drive, Cranbury, NJ 08512. (Package Insert footer shows “US License No X” — this draft uses License 2328 from the approval letter.)

Where this is taking place

Commercial labelled door today: United States — FDA-labelled KRESLADI for pediatric severe LAD-I without an available HLA-matched sibling donor, administered at a specialized / qualified treatment center after mobilization and apheresis, product manufacturing from the child’s own cells, full myeloablative conditioning, and planned infection prophylaxis. Company materials describe making KRESLADI available to eligible patients in the United States; secondary company / trade coverage has described a phased, limited-center commercial start with enrollment guided into late 2026 and first commercial infusions guided into 2027. Treat mid-September 2026 as a launch-window / referral conversation, not a guarantee every centre can infuse every day. This is a pediatric immunology / transplant-centre gene therapy conversation — not a retail pharmacy pickup and not a DIY import.

Outside the United States: As of this draft, no confirmed Health Canada Notice of Compliance, European Commission marketing authorisation, MHRA licence, TGA listing, Swissmedic authorisation, or PMDA/MHLW licence for KRESLADI / marnetegragene autotemcel. Do not import on your own.

RP-L201-0318 — NCT03812263 — Open-label, single-arm, multicenter Phase 1/2 study. Lead sponsor: Rocket Pharmaceuticals Inc. CT.gov status at draft time: COMPLETED. Actual enrolment 9. Actual start 30 Aug 2019; actual primary completion 12 Sep 2023; actual study completion 12 Sep 2023. Countries with listed sites: United States, United Kingdom, and Spain. Honesty: Completed pivotal study ≠ open enrolment. Foreign trial sites ≠ foreign marketing authorisation. Post-marketing confirmatory obligations remain under accelerated approval. A California CIRM access-and-affordability plan document exists for eligible California residents — that is a state-specific access pathway description, not a multi-country licence.

The practical commercial door in the US is a pediatric immunology / bone-marrow transplant / gene-therapy centre working with Rocket to confirm severe LAD-I (ITGB2), document no available HLA-matched sibling donor, plan mobilization / manufacturing / conditioning / infusion, and arrange patient-services / payer logistics — not treating biomarker increases as permission to ignore infection and engraftment monitoring.

Approval matrix

Access by country

• United States: Ask a pediatric immunology / bone-marrow transplant / gene-therapy team about referral for FDA-labelled KRESLADI. Labelled 26 March 2026 (accelerated) for pediatric patients with severe LAD-I due to biallelic ITGB2 variants without an available HLA-matched sibling donor for allogeneic HSCT. Path: HSC mobilization + apheresis → manufacturing → full myeloablative conditioning → one-time IV infusion of autologous product (minimum 2.8×10⁶ CD34+ cells/kg; up to two lots may be used to meet the minimum). Verify patient identity on the bag(s) before infusion. Do not sample, alter, irradiate, or use an in-line blood filter / infusion pump. Store frozen vapor-phase liquid nitrogen ≤ −150 °C until thaw. NDC 83537-034-01 (50 mL infusion bag and metal cassette). Suspected adverse reactions / product concerns: Rocket Pharmaceuticals 1-800-982-2410 or FDA MedWatch 1-800-FDA-1088. No list price or copay dollars in this article. Company/trade coverage may discuss launch timing — disclose the phased QTC / 2027 first-infusion guidance honestly with the centre. This is US labelled supply through specialized centres, not a DIY import.

• Canada: KRESLADI authorisation not confirmed. Ask the Canadian pediatric immunology clinic what legal paths exist in Canada when a Canadian KRESLADI label does not yet exist.

• European Union / United Kingdom / Australia / Japan / other countries: Regulator authorisation not confirmed in this draft. Completed trial sites are not a commercial foreign carton. Do not import on your own.

• If your regulator has not authorised it: do not import on your own. Ask the local clinician about documented special-access / named-patient rules, referral to a centre in a labelled country, or waiting — without treating a US autologous bag as a foreign carton.

Who is eligible (from the US label)

This is a pediatric severe LAD-I (ITGB2) without matched sibling donor conversation on the Package Insert — one-time autologous gene therapy after conditioning — not a claim that long-term survival benefit is already fully confirmed.

United States (Package Insert, revised March 2026):

• Indication: Pediatric severe LAD-I due to biallelic ITGB2 variants without an available HLA-matched sibling donor for allogeneic HSCT.
• Accelerated approval: Based on neutrophil CD18 and CD11a surface-expression increases; confirmatory clinical benefit still required.
• Recommended dosage: One-time IV; minimum 2.8×10⁶ CD34+ cells/kg.
• Contraindication: None listed on Highlights.
• Warnings: Serious infections; veno-occlusive disease; neutrophil engraftment failure (rescue cells); delayed platelet engraftment; LVV-mediated insertional oncogenesis (monitor ≥15 years); hypersensitivity; anti-retroviral timing; HIV PCR assay interference; do not donate blood/organs/tissues/cells.
• Most common non-laboratory adverse reactions (≥30%): mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, skin infection.
• Most common laboratory adverse reactions (≥30%): hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, AST increased, ALT increased.
• Anti-retrovirals: Do not take for one month prior to mobilization (or for the elimination window) until apheresis cycles complete.
• Pediatrics: Established in the studied pediatric severe LAD-I population (trial ages about 9.8 months to 9.8 years on PI); discuss exact age fit with the centre.
• Geriatrics: Not established for this indication.

Not labelled on sources confirmed for this draft:

• Adults (this indication is pediatric).
• Patients who have an available HLA-matched sibling donor (excluded from labelled population).
• Canadian, EU, UK, Japanese, Australian, or Swiss KRESLADI marketing authorisations (not confirmed here).
• Proven confirmatory long-term clinical benefit beyond the accelerated surrogate (still required).
• Treating NCT03812263 as open commercial enrolment.

What the pivotal study showed (Prescribing Information)

Use the Package Insert for a prescription conversation. Journals are supportive reading.

RP-L201-0318 — NCT03812263 (USPI Study):

• Open-label, single-arm, multicenter; 9 pediatric patients with molecularly confirmed ITGB2-associated severe LAD-I.
• Severe LAD-I definition on PI: neutrophil CD18 <2% or CD11a and/or CD11b <2% (if CD18 ≥2%), documented biallelic ITGB2 mutations, and clinical history consistent with severe LAD-I or known family history; HLA-identical sibling donor excluded.
• Median age 42 months (range 9.8–117 months); median dose 4.3×10⁶ CD34+ cells/kg (range 2.8–10×10⁶); median follow-up 4.2 years (range 3.6–5.7).

USPI efficacy (surrogate):

Trial-status honesty: CT.gov status COMPLETED. Accelerated label rests on biomarker surrogates — confirmatory clinical outcomes remain required.

How it is taken (US label — keep this exact)

Research team (from primary sources only)

• Applicant / manufacturer: Rocket Pharmaceuticals, Inc., Cranbury, NJ — U.S. License 2328 (approval letter).
• Pivotal study sponsor: Rocket Pharmaceuticals Inc. (NCT03812263 / RP-L201-0318).
• Letter attention: Sanchali Kasbekar, PharmD (approval letter).
• Patient / centre contact on label: Rocket Pharmaceuticals 1-800-982-2410 (AE reporting; product-receipt concerns; malignancy reporting guidance on PI).
• Names and phones below are limited to what appears on the Package Insert, FDA press / approval letter, ClinicalTrials.gov, and clearly labelled company materials.

Sources

1. FDA — FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I (26 Mar 2026).
2. FDA — KRESLADI product page (STN 125806) + Package Insert (revised 3/2026).
3. FDA — March 26, 2026 Approval Letter — KRESLADI (STN BLA 125806/0; License 2328).
4. ClinicalTrials.gov — NCT03812263 (RP-L201-0318).
5. Rocket Pharmaceuticals — FDA approval company announcement (27 Mar 2026).
6. DailyMed — KRESLADI (marnetegragene autotemcel) listing (cross-check).

Not medical advice. Talk with a clinician who knows the full history before any treatment decision. Authorized is not funded.