Alofisel (darvadstrocel) / Takeda - LARVOL DELTA

When one trial is not enough: Lessons from darvadstrocel approval and withdrawal. (PubMed, Gastroenterology) - No abstract available

Journal

CHAZAM: Study on the Treatment of Anal Fistulas Using Alofisel Versus Fat Autologous Stem Cells (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Nantes University Hospital | Trial completion date: Jun 2025 ➔ Jun 2027

Trial completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study) (ASCRS 2026) - No abstract available

Clinical • Crohn's disease • Gastroenterology • Immunology

Darvadstrocel in Patients With Crohn's Disease With Complex Perianal Fistulas: The ADMIRE CD II Phase 3 Randomized Trial. (PubMed, Gastroenterology) - P3 | "ADMIRE CD II did not meet its primary endpoint of combined remission at week 24, with no statistically significant difference between darvadstrocel and placebo. No new safety signals were identified for darvadstrocel."

Journal • P3 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

The societal burden of perianal fistulizing Crohn's disease: high costs driven by absenteeism in a prospective nationwide Dutch cohort study (ECCO-IBD 2026) - "Radiological assessments and endoscopic procedures contributed €400 (357-444) while surgical interventions, including treatment with Darvadstrocel, amounted to €5.421 (3877-6965) per patient per year...Costs are primarily driven by biological therapies and productivity loss due to absenteeism. Absenteeism consistently accounts for more than 25% of total costs, underscoring the impact of active pCD on the ability to work and the overall societal burden."

Clinical • Crohn's disease • Immunology • Inflammatory Bowel Disease

Early changes in MAGNIFI and fistula volumetry are biomarkers that predicts clinical outcomes in perianal fistulizing Crohn’s disease. A multicentric study. (ECCO-IBD 2026) - "Conclusion Early MRI changes, combining reduction in the MAGNIFI score and the active fistula volume, are associated with subsequent clinical remission in patients with PFD treated with darvadstrocel. Prospective validation in larger cohorts and using therapies with different mechanism of action is warranted."

Biomarker • Clinical • Clinical data • Crohn's disease • Immunology • Inflammatory Bowel Disease

Therapeutic potential and mechanistic insights into adipose-derived stem cells and mesenchymal stem cell-derived exosomes in patients with Crohn's disease-associated fistulas: challenges and future perspectives. (PubMed, Stem Cell Res Ther) - "Preclinical studies, clinical trials, and systematic reviews have evaluated the safety and efficacy of these approaches, with ADSCs-commercially available as Darvadstrocel-emerging as one of the most promising options...Exosome therapies still lack a dedicated approval pathway, and GMP-scale purification is still confined to a handful of facilities, driving prices beyond current reimbursement limits. Future phase III trials must therefore embed economic modeling and adopt composite end points that link molecular engagement to MRI-verified fistula healing and patient-reported outcomes."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Darvadstrocel: real-world clinical outcomes and economic impact in the Spanish national health system. (PubMed, Ann Gastroenterol) - "Darvadstrocel demonstrated high effectiveness and safety in real-world clinical practice for patients with CD and complex perianal fistulas, with remission rates consistent with previous studies. The implementation of the OBPM linked to health outcomes proved to be a valuable tool for funding innovative therapies."

Clinical data • HEOR • Journal • Real-world evidence • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

A Study to Check How Often People Treated With Darvadstrocel for Crohn's Disease Are Diagnosed With Cancer (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Takeda | N=5850 ➔ 0 | Trial completion date: Nov 2026 ➔ Dec 2027 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: Nov 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Oncology

A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease (clinicaltrials.gov) - P3 | N=7 | Terminated | Sponsor: Takeda | Trial completion date: Dec 2025 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ May 2025; Sponsor decision

Trial completion date • Trial primary completion date • Trial termination • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pediatrics

Conformation-adaptive Lipids for mRNA-Based Gene Editor Delivery via Lipid Nanoparticles (LNPs) in Non-Human Primates: Achieving a Wide Therapeutic Window (ASGCT 2025) - "Further in vivo studies in mice and rats confirmed favorable biodistribution and toxicity profiles, with top candidates—CX-322, CX-571, CX-108, and CX-601—showing >99% liver-specific distribution and no significant impact on body weight and liver panel parameters...Overall, these conformation-adaptive ionizable LNPs offer a potent, safe approach for in vivo CRISPR/Cas9-based genome editing, underscoring their potential as a clinical platform with a broad therapeutic window. Disease Focus of Abstract:Liver Diseases"

Lipid Nanoparticle • Hepatology • Infectious Disease

A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease (clinicaltrials.gov) - P3 | N=7 | Active, not recruiting | Sponsor: Takeda | Completed ➔ Active, not recruiting | Trial completion date: May 2024 ➔ Dec 2025 | Trial primary completion date: May 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pediatrics

ASPIRE: A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula (clinicaltrials.gov) - P4 | N=53 | Terminated | Sponsor: Takeda | Trial completion date: Mar 2026 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Feb 2025; Sponsor decision

Trial completion date • Trial primary completion date • Trial termination • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease (clinicaltrials.gov) - P3 | N=7 | Completed | Sponsor: Takeda | Recruiting ➔ Completed | N=20 ➔ 7 | Trial completion date: Dec 2025 ➔ May 2024 | Trial primary completion date: Jun 2025 ➔ May 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pediatrics

Effectiveness and safety of mesenchymal stem cell treatment in fistulizing Crohn’s disease: predictors of treatment success (ECCO-IBD 2025) - "We aimed to examine the usability of darvadstrocel therapy in managing perianal CD...The safety profile is reassuring, and patients’ satisfaction is high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success."

Clinical • Crohn's disease • Immunology • Inflammatory Bowel Disease

Efficacy and safety of Darvadstrocel (allogeneic stem cell therapy) at 6 and 12 months in refractory complex perianal fistulas in Crohn's disease. Real clinical practice in the Northwest of Spain. (ECCO-IBD 2025) - "Conclusion This study supports the efficacyand safety of Darvadstrocell for refractory perianal CD fistulas with combined success rates of 69% and 76% at 6 and 12 months. Technical and individual characteristics for a better outcome remain unknown, but a shorter interval between surgical times was associated with greater response."

Clinical • Crohn's disease • Immunology • Inflammatory Bowel Disease

Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in patients with complex perianal fistulas in Crohn's disease. (PubMed, BMC Gastroenterol) - "This novel approach enabled pooled data from a clinical trial and real-world settings to predict long-term effectiveness of DVS versus SoC in patients with complex CPF."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

CHAZAM: Study on the Treatment of Anal Fistulas Using Alofisel Versus Fat Autologous Stem Cells (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Nantes University Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease

“…Update of sections 4.8 and 5.1 of the SmPC in order to update the safety information, based on pooled safety data from the two phase 3 controlled studies (ADMIRECD & ADMIRE-CD II)…The Annex II is updated accordingly. In addition, the MAH took the opportunity to introduce minor changes to the PI, including to section 4.2 of the SmPC and to the Package Leaflet.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 25 – 28 Nov 2024: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Crohn's disease • Inflammatory Bowel Disease

How Could ATMPs Demonstrate an Economic Benefit for Payers and What Are the Real-World Examples of This? (ISPOR-EU 2024) - "Two ATMPs, Yescarta and Alofisel, were selected to illustrate contrasting examples from a P&R perspective. The level of clinical benefit is the key factor in HTA decisions for ATMPs. ATMPs often lack sufficient evidence to demonstrate clinical and economic benefit at launch. Alternative reimbursement schemes, like coverage with evidence development, and payment methods are used to provide access despite uncertainties."

Clinical • HEOR • Real-world • Real-world evidence

Evaluation of the Effectiveness and Safety of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease: An International Real-Life Retrospective Multicentre Cohort Study. (PubMed, Aliment Pharmacol Ther) - "Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success."

Clinical • Journal • Retrospective data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

REAL-LIFE EFFECTIVENESS OF ALLOGENEIC EXPANDED ADIPOSE-DERIVED MESENCHYMAL STEM CELL THERAPY FOR PERIANAL FISTULIZING REFRACTORY CROHN’S DISEASE (UEGW 2024) - "This real-life based study shares additional experience on the effectiveness and safety of a single local injection of darvadstrocel for treating complex perianal fistula in a particularly severe and refractory cohort of patients with CD. Clinical remission was achieved in 47.2 % of patients at week 24 and combined remission in one more than 4 out of 10 patients at 52 weeks. Long-term larger studies are needed to better identify predictors of sustained fistula healing using darvadstrocel in perianal fistulizing CD."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • CD2

META-ANALYSIS: REAL-WORLD EFFECTIVENESS AND SAFETY OF DARVADSTROCEL FOR COMPLEX PERIANAL FISTULIZING CROHN’S DISEASE (UEGW 2024) - "Real-world evidence supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies reported high fistula healing rates that can be sustained long-term in most patients, with high homogeneity across studies. Darvadstrocel showed a favourable safety profile."

Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Darvadstrocel for complex perianal fistulas in Crohn's disease: A systematic review and meta-analysis. (PubMed, United European Gastroenterol J) - "Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile."

Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Real-life effectiveness of allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulizing refractory Crohn's disease: allogeneic MSC therapy in perianal fistulizing CD. (PubMed, Clin Res Hepatol Gastroenterol) - "In this real-world setting, a successful response to darvadstrocel therapy based on clinical remission was reported in around half of the patients and combined remission including radiological assessment in more than 4 out of 10 patients."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease