Takeda Pharmaceutical Company Limited announced that it has received approval from the Japan Ministry of Health, Labour and Welfare to manufacture and market Alofisel (darvadstrocel) - development code: Cx601 - for the treatment of complex perianal fistulas in patients with non-active or mildly active luminal Crohn’s disease (CD). This product is indicated for the treatment of patients who have shown an inadequate response to at least one existing medicinal treatment.

CD is a chronic inflammatory disease of the digestive system, which affects an estimated 70,700 people in Japan. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. In a survey commissioned and conducted by the European Federation of Crohn's & Ulcerative Colitis Associations (EFCCA), in collaboration with Takeda, CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life, including the ability to do sports, work and employment, dating and sexual life. Patients also reported feeling more unhygienic, uncomfortable, and guilty about their condition compared to CD patients without perianal fistulas.

“We are delighted that Alofisel has been approved in Japan for the treatment of complex perianal fistulas in Crohn’s disease patients. Complex perianal fistulas are a challenging complication of Crohn’s disease, and the approval of the first expanded human allogeneic adipose-derived mesenchymal stem cell therapy in Japan offers a potential cell-mediated closure option to patients who do not respond to conventional or biologic therapies,” said Naoyoshi Hirota, general manager of Takeda Development Center Japan.

Study Darvadstrocel-3002 was a phase 3, multicenter, open-label, uncontrolled study investigating the efficacy (24 and 52 weeks) and safety (156 weeks) of Alofisel for the treatment of complex perianal fistulas in 22 Japanese adult patients with non-active/mildly active luminal CD.

ADMIRE-CD was a randomized, double-blind, controlled, phase 3 trial investigating the efficacy and safety of Alofisel for the treatment of complex perianal fistulas in 212 adult patients with non-active/mildly active luminal CD.1 A significantly greater proportion of patients in the Alofisel group compared to the control group achieved the primary endpoint of combined remission at a 24 week follow-up (51.5% vs 35.6%; 97.5% CI 0.5-31.2; P =0.021), and this was maintained over 52 weeks (56.3% vs 38.6%; 95% CI 4.2-31.2; P =0.01).11 Alofisel treatment was well-tolerated over 52 weeks, with a similar safety profile in the Alofisel group compared to the control group.

Alofisel is the first expanded human allogeneic adipose-derived mesenchymal stem cell therapy to be approved in Japan. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option with the potential of cell-mediated closure for complex perianal fistulas in patients with non-active or mildly active luminal Crohn’s disease that have shown an inadequate response to at least one existing medicinal treatment.

Alofisel is a suspension of allogeneic (or donor-derived) expanded adipose-derived stem cells (eASC) for the treatment of complex perianal fistulas in adult patients with non-active or mildly active luminal CD.