Takeda Submits New Drug Application to Manufacture and Market Darvadstrocel In Japan for Treatment of Complex Perianal Fistulas in Adult Patients with Crohn’s Disease

Takeda Submits New Drug Application to Manufacture and Market Darvadstrocel

In Japan for Treatment of Complex Perianal Fistulas in Adult Patients with Crohn’s Disease

−       Takeda Applies for Approval for the Company’s First Allogeneic Stem Cell Therapy in Japan

−       If Approved, Darvadstrocel Would Offer a Potential Cell-Mediated Closure Option for Adult Patients in Japan Who Do Not Respond to Conventional or Biologic Therapies for Complex Perianal Fistulas in Crohn’s Disease[i]^,[ii]

Osaka, JAPAN, February 10, 2021 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that it has submitted an application to the Japanese Ministry of Health, Labour and Welfare to manufacture and market darvadstrocel (development code: Cx601) for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease (CD).

The application filing included data from two trials, the Japanese Study Darvadstrocel-3002 and the ADMIRE-CD trial, conducted in Europe and Israel.^i,[iii] Study Darvadstrocel-3002 is a Phase 3, multicenter, open-label, uncontrolled study investigating the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in 22 Japanese adult patients with non-active/mildly active luminal CD.ⁱⁱⁱ Results from Study Darvadstrocel-3002 will be presented at a scientific meeting in the near future. ADMIRE-CD was a randomized, double-blind, controlled, Phase 3 trial investigating the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in 212 adult patients with non-active/mildly active luminal CD.ⁱ

Naoyoshi Hirota, General Manager of Takeda Development Center Japan said, “Complex perianal fistulas in Crohn's disease place a significant burden on patients and are a serious complication that greatly impacts quality of life.[iv]^,[v] We are extremely grateful to the patients and healthcare professionals who cooperated in the development of this investigational medicine, and we are proud to have taken this first step toward the potential approval of a cell-mediated closure option^i,ii for adult Crohn’s disease patients with complex perianal fistulas in Japan.”

Darvadstrocel received an orphan drug designation from Japan's Ministry of Health, Labour and Welfare on March 13, 2019 for potential efficacy, effects, or performance in treating complex perianal fistulas in adult patients with CD.[vi] Darvadstrocel received central marketing authorization approval in Europe in March 2018 for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal CD.[vii]

[i] Panés J, García-Olmo D, Van Assche G, Colombel JF, et al. ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016;24;388(10051):1281-90.

[ii] Alofisel Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/alofisel-epar-product-information_en.pdf. Last updated November 24, 2020. Last accessed February 2021.

[iii] Phase 3 Study of Cx601 in Subjects With Complex Perianal Fistulising Crohn's Disease. Available at https://clinicaltrials.gov/ct2/show/NCT03706456. Last updated: October 5, 2020. Last accessed February 2021.

[iv] Mahadev S, Young JM, Selby W, et al., Quality of life in perianal Crohn's disease: what do patients consider important? Dis Colon Rectum. 2011; 54(5): 579-585.

[v] Aguilera-Castro L, Ferre-Aracil C, Garcia-Garcia-de-Paredes A, Rodriguez-de-Santiago E, Lopez-Sanroman A. Management of complex perianal Crohn’s disease. Ann Gastroenterol. 2017;30:33-44.

[vi] Orphan drug list. Available at:

https://www.nibiohn.go.jp/nibio/part/promote/orphan_support/index.html#hyodata001 Last updated: June 23, 2020. Last accessed February 2021.

[vii] Alofisel European public assessment report summary. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/alofisel. Last updated: November 24, 2020. Last accessed February 2021.