OSAKA, Japan and CAMBRIDGE, MA, USA I December 13, 2024 I Takeda (TSE:4502/NYSE:TAK) today announced that the company is working with the European Medicines Agency (EMA) to voluntarily withdraw the marketing authorization of Alofisel® (darvadstrocel), a treatment for complex perianal fistulas in patients with Crohn’s disease, in the European Union (EU).
Alofisel is an allogeneic stem cell therapy that is approved in the EU for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.1 Alofisel should be used only after conditioning of the fistulas.
The initial authorization of Alofisel in the EU was based on results from the Phase 3 ADMIRE-CD placebo-controlled registrational study.1 Given the small population size (n = 212) and modest benefit observed in the ADMIRE-CD study (a difference of 15.8% between the modified intention-to-treat population versus placebo at 24 weeks), Takeda agreed to provide results from ADMIRE-CD II, a study that was underway, to confirm Alofisel’s efficacy.1-3
In October 2023, Takeda communicated ADMIRE-CD II, a randomized placebo-controlled study of 568 patients with complex CPF, did not meet its primary endpoint of combined remission at 24 weeks.3-5 Additional results, which were presented at the European Crohn’s and Colitis Organisation Congress 2024 in February, showed no statistical differences in any of the secondary endpoints.5 The safety profile for Alofisel was consistent with prior studies as no new, emerging safety signals were identified.2,4,5
“Guided by our values and the needs of patients living with this difficult-to-treat condition, we engaged the EMA, as well as health care professionals and others in the community, to review the totality of data and the role of our medicine,” said Ramona Sequeira, president, Global Portfolio Division, at Takeda. “Those valuable discussions indicated that despite the conflicting results across our data, the clinical benefit of Alofisel is no longer sufficient to justify its continued use in the EU. We recognize the difficulty of this outcome for patients and will work closely with the Crohn’s Perianal Fistulas (CPF) community during this transition.”
In addition to the EU, Takeda is engaging health authorities about this outcome in countries where Alofisel is currently approved, keeping the best interest of patients at the forefront.
Takeda is committed to continuing to share data from clinical and observational studies for the benefit of patients and the entire health care community, with the hope that these insights can contribute to scientific advancements in complex CPF.
Health care professionals with medical-related questions about Alofisel should contact Takeda Medical Information at medinfoEMEA@takeda.com or medinfoAPAC@takeda.com. Patients should consult their treating health care professional if they have questions.
About Alofisel®
Alofisel® (darvadstrocel) is a dispersion for injection of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue (expanded adipose stem cells – eASC) for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease.
Therapeutic Indications
Alofisel is indicated for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used only after conditioning of the fistulas.
Important Safety Information
Contraindications
Hypersensitivity to the active substance, bovine serum or to any of the excipients.
Special warnings and special precautions for use
Alofisel may contain trace amounts of either gentamicin or benzylpenicillin and streptomycin. This should be considered in patients with known hypersensitivity to these classes of antibiotics. Local anaesthesia is not recommended due to the unknown effect of local anaesthetics on the injected cells.
The injection of any substance other than sodium chloride 9 mg/mL (0.9%) solution (e.g. hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions) through the fistula tracts is not allowed before, during, or after the injection of Alofisel as these may compromise the viability of the cells.
Alofisel must not be administered using a needle thinner than 22G. Thinner gauge needles can cause cell disruption during injection and may compromise cell viability and, therefore, may affect efficacy of treatment.
As Alofisel is a living stem cell therapy it cannot be sterilised, a risk of transmission of infectious agents exists, although the risk is considered to be low and controlled in the manufacturing process. Healthcare professionals administering darvadstrocel must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed.
Alofisel should only be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which darvadstrocel is indicated.
Patients treated with Alofisel must not donate blood, organs, tissues and cells for transplantation. The traceability requirements of cell-based therapy medicinal products must apply.
Fertility, Pregnancy & Lactation
No data is available from the use of darvadstrocel in pregnant women. Darvadstrocel is not recommended during pregnancy and in women of childbearing potential who are not using contraception. As a precautionary measure, darvadstrocel is not recommended for administration during breast-feeding.
Undesirable effects
Based on clinical trial and post-marketing data, the most commonly reported adverse drug reactions were anal abscess, proctalgia and anal fistula with the most commonly reported serious adverse drug reactions of anal abscess and anal fistula.
Procedural pain is associated to conditioning reactions occurring up to seven days after the fistula preparation for treatment administration.
For EU audiences, please see the Summary of Product Characteristics (SmPC)
for Alofisel®.
Please consult with your local regulatory agency for approved labeling in your country.
Takeda in Gastroenterology
Takeda is committed to meeting the very real needs of those living with gastrointestinal (GI) diseases. We believe that GI and liver diseases are life-disrupting conditions. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With more than 35 years of experience in gastroenterology, Takeda has made significant strides in addressing patient needs with treatments for inflammatory bowel disease, eosinophilic esophagitis, acid-related diseases, short bowel syndrome and motility disorders. We are making significant strides toward closing the gap on new areas of unmet need. Together with researchers, patient groups and others, we are working to advance scientific research and clinical medicine in GI.
About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.
References
- Alofisel. Summary of Product Characteristics. Takeda; September 2023. Accessed October 18, 2024. https://www.ema.europa.eu/en/documents/product-information/alofisel-epar-product-information_en.pdf
- Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020.
- National Library of Medicine. Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants with Crohn’s Disease (CD) (ADMIRE-CD-II). ClinicalTrials.gov website. Accessed October 22, 2024. https://www.clinicaltrials.gov/study/NCT03279081
- Takeda Pharmaceutical Company Ltd. Takeda Announces Topline Results of Phase 3 ADMIRE-CD II Trial of Alofisel® (darvadstrocel) in Complex Crohn’s Perianal Fistulas. Takeda Pharmaceuticals Website. Accessed October 22, 2024. https://www.takeda.com/newsroom/newsreleases/2023/takeda-announces-topline-results-of-phase-3-admire-cd-ii-trial-of-alofisel-darvadstrocel-in-complex-crohns-perianal-fistulas/
- Serclova Z, García-Olmo D, Chen ST, et al. OP18 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. J Crohns Colitis. 2024;18(1):i34-i35. doi:10.1093/ecco-jcc/jjad212.0018.
SOURCE: Takeda Pharmaceutical Co
Post Views: 283
OSAKA, Japan and CAMBRIDGE, MA, USA I December 13, 2024 I Takeda (TSE:4502/NYSE:TAK) today announced that the company is working with the European Medicines Agency (EMA) to voluntarily withdraw the marketing authorization of Alofisel® (darvadstrocel), a treatment for complex perianal fistulas in patients with Crohn’s disease, in the European Union (EU).
Alofisel is an allogeneic stem cell therapy that is approved in the EU for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.1 Alofisel should be used only after conditioning of the fistulas.
The initial authorization of Alofisel in the EU was based on results from the Phase 3 ADMIRE-CD placebo-controlled registrational study.1 Given the small population size (n = 212) and modest benefit observed in the ADMIRE-CD study (a difference of 15.8% between the modified intention-to-treat population versus placebo at 24 weeks), Takeda agreed to provide results from ADMIRE-CD II, a study that was underway, to confirm Alofisel’s efficacy.1-3
In October 2023, Takeda communicated ADMIRE-CD II, a randomized placebo-controlled study of 568 patients with complex CPF, did not meet its primary endpoint of combined remission at 24 weeks.3-5 Additional results, which were presented at the European Crohn’s and Colitis Organisation Congress 2024 in February, showed no statistical differences in any of the secondary endpoints.5 The safety profile for Alofisel was consistent with prior studies as no new, emerging safety signals were identified.2,4,5
“Guided by our values and the needs of patients living with this difficult-to-treat condition, we engaged the EMA, as well as health care professionals and others in the community, to review the totality of data and the role of our medicine,” said Ramona Sequeira, president, Global Portfolio Division, at Takeda. “Those valuable discussions indicated that despite the conflicting results across our data, the clinical benefit of Alofisel is no longer sufficient to justify its continued use in the EU. We recognize the difficulty of this outcome for patients and will work closely with the Crohn’s Perianal Fistulas (CPF) community during this transition.”
In addition to the EU, Takeda is engaging health authorities about this outcome in countries where Alofisel is currently approved, keeping the best interest of patients at the forefront.
Takeda is committed to continuing to share data from clinical and observational studies for the benefit of patients and the entire health care community, with the hope that these insights can contribute to scientific advancements in complex CPF.
Health care professionals with medical-related questions about Alofisel should contact Takeda Medical Information at medinfoEMEA@takeda.com or medinfoAPAC@takeda.com. Patients should consult their treating health care professional if they have questions.
About Alofisel®
Alofisel® (darvadstrocel) is a dispersion for injection of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue (expanded adipose stem cells – eASC) for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease.
Therapeutic Indications
Alofisel is indicated for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used only after conditioning of the fistulas.
Important Safety Information
Contraindications
Hypersensitivity to the active substance, bovine serum or to any of the excipients.
Special warnings and special precautions for use
Alofisel may contain trace amounts of either gentamicin or benzylpenicillin and streptomycin. This should be considered in patients with known hypersensitivity to these classes of antibiotics. Local anaesthesia is not recommended due to the unknown effect of local anaesthetics on the injected cells.
The injection of any substance other than sodium chloride 9 mg/mL (0.9%) solution (e.g. hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions) through the fistula tracts is not allowed before, during, or after the injection of Alofisel as these may compromise the viability of the cells.
Alofisel must not be administered using a needle thinner than 22G. Thinner gauge needles can cause cell disruption during injection and may compromise cell viability and, therefore, may affect efficacy of treatment.
As Alofisel is a living stem cell therapy it cannot be sterilised, a risk of transmission of infectious agents exists, although the risk is considered to be low and controlled in the manufacturing process. Healthcare professionals administering darvadstrocel must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed.
Alofisel should only be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which darvadstrocel is indicated.
Patients treated with Alofisel must not donate blood, organs, tissues and cells for transplantation. The traceability requirements of cell-based therapy medicinal products must apply.
Fertility, Pregnancy & Lactation
No data is available from the use of darvadstrocel in pregnant women. Darvadstrocel is not recommended during pregnancy and in women of childbearing potential who are not using contraception. As a precautionary measure, darvadstrocel is not recommended for administration during breast-feeding.
Undesirable effects
Based on clinical trial and post-marketing data, the most commonly reported adverse drug reactions were anal abscess, proctalgia and anal fistula with the most commonly reported serious adverse drug reactions of anal abscess and anal fistula.
Procedural pain is associated to conditioning reactions occurring up to seven days after the fistula preparation for treatment administration.
For EU audiences, please see the Summary of Product Characteristics (SmPC)
for Alofisel®.
Please consult with your local regulatory agency for approved labeling in your country.
Takeda in Gastroenterology
Takeda is committed to meeting the very real needs of those living with gastrointestinal (GI) diseases. We believe that GI and liver diseases are life-disrupting conditions. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With more than 35 years of experience in gastroenterology, Takeda has made significant strides in addressing patient needs with treatments for inflammatory bowel disease, eosinophilic esophagitis, acid-related diseases, short bowel syndrome and motility disorders. We are making significant strides toward closing the gap on new areas of unmet need. Together with researchers, patient groups and others, we are working to advance scientific research and clinical medicine in GI.
About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.
References
- Alofisel. Summary of Product Characteristics. Takeda; September 2023. Accessed October 18, 2024. https://www.ema.europa.eu/en/documents/product-information/alofisel-epar-product-information_en.pdf
- Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020.
- National Library of Medicine. Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants with Crohn’s Disease (CD) (ADMIRE-CD-II). ClinicalTrials.gov website. Accessed October 22, 2024. https://www.clinicaltrials.gov/study/NCT03279081
- Takeda Pharmaceutical Company Ltd. Takeda Announces Topline Results of Phase 3 ADMIRE-CD II Trial of Alofisel® (darvadstrocel) in Complex Crohn’s Perianal Fistulas. Takeda Pharmaceuticals Website. Accessed October 22, 2024. https://www.takeda.com/newsroom/newsreleases/2023/takeda-announces-topline-results-of-phase-3-admire-cd-ii-trial-of-alofisel-darvadstrocel-in-complex-crohns-perianal-fistulas/
- Serclova Z, García-Olmo D, Chen ST, et al. OP18 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. J Crohns Colitis. 2024;18(1):i34-i35. doi:10.1093/ecco-jcc/jjad212.0018.
SOURCE: Takeda Pharmaceutical Co
Post Views: 283
