Alofisel (darvadstrocel) / Takeda - LARVOL DELTA

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

The potential for medical therapies to address fistulizing Crohn's disease: a state-of-the-art review. (PubMed, Expert Opin Biol Ther) - "Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials...Current options include adalimumab and certolizumab pegol combination therapies, as well as small molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas are mesenchymal stem cells such as Darvadstrocel (Alofisel) an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options."

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

Allogenic Stem Cells in Anal Fistulas of Crohn's Disease: From Promising Premises to Real Life Experience. (PubMed, Inflamm Bowel Dis) - "Allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate."

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

INSPIRE: PRELIMINARY DATA FROM AN OBSERVATIONAL POST-MARKETING REGISTRY ON THE EFFECTIVENESS AND SAFETY OF DARVADSTROCEL IN PATIENTS WITH CROHN’S DISEASE AND COMPLEX PERIANAL FISTULAS (DDW 2024) - "These preliminary data are consistent with the pivotal ADMIRE-CD study and demonstrate a single dose of DVS in patients with complex CPF is associated with positive clinical outcomes in up to 80% of patients, and a favorable safety profile, both of which are maintained after 12 months. The inherent limitations of registry-based studies mean that these data should be interpreted with caution. However, the ongoing INSPIRE study will provide longer follow-up data to confirm these observations with respect to any study limitations."

Clinical • P4 data • Breast Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Oncology • Ovarian Cancer • Solid Tumor

EFFICACY AND SAFETY OF DARVADSTROCEL TREATMENT IN PATIENTS WITH COMPLEX PERIANAL FISTULAS AND CROHN’S DISEASE: RESULTS FROM THE GLOBAL ADMIRE-CD II PHASE 3 STUDY (DDW 2024) - "The efficacy outcomes assessed did not statistically differ between DVS and placebo, and the placebo response rate (with fistula preconditioning) was higher than expected. Post hoc analyses revealed lower placebo response rates in patients randomized before COVID-19 (similar to the pivotal ADMIRE-CD I study) than the overall placebo arm. DVS was well tolerated."

Clinical • P3 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease

4435: Immunology, Microbiology & Inflammatory Bowel Diseases (IMIBD) Section Distinguished Abstract Plenary (DDW 2024) - "Description: This session highlights the best of the best in basic and clinical science research submitted to DDW 2024. Learning Objectives: Describe the efficacy and safety of guselkumab, darvadstrocel, and risankizumab for the treatment of IBD"

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Long-term Follow-up Study With Darvadstrocel in the Treatment of Complex Perianal Fistula (clinicaltrials.gov) - P3 | N=151 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

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

A new treatment option for complex perianal fistulas in Crohn's disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan (PubMed, Nihon Yakurigaku Zasshi) - "By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced."

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

Insights into treatment of complex Crohn's perianal fistulas. (PubMed, BMC Proc) - "One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease...Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition."

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

Reply to comments on: "Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn's disease-A prospective nationwide multicenter cohort study". (PubMed, Wien Klin Wochenschr) - No abstract available

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

Comments on: "Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn's disease-A prospective nationwide multicenter cohort study". (PubMed, Wien Klin Wochenschr) - No abstract available

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