Alofisel▼ (darvadstrocel) Shows Clinical Remission Rate at Six-Months in the Real-World INSPIRE Study Interim Analysis Consistent with the Pivotal Clinical ADMIRE-CD Study1,2

- Data on Patients with Complex Crohn’s Perianal Fistulas Were Presented at the European Crohn’s and Colitis Organisation (ECCO) 2022 Congress1

- INSPIRE is the First Observational, Multicenter, Post-Approval, Open-Enrollment Study Designed to Evaluate the Real-World Effectiveness and Safety of Alofisel (darvadstrocel)1

- Approved in the European Union/European Economic Area, Israel, Switzerland, United Kingdom and Japan, Alofisel, an Expanded Human Allogeneic Adipose-Derived Mesenchymal Stem Cell Therapy, Offers a Potential Cell-Mediated Closure Option for Patients with Complex Crohn’s Perianal Fistulas Who Have Shown an Inadequate Response to at Least One Conventional or Biologic Therapy3,4,5,6,7,8

OSAKA, Japan & CAMBRIDGE, Massachusetts--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced the first six-month interim analysis results from INSPIRE, in which clinical remission* was observed in 65% of patients in both cohorts who were evaluated at 6 months.1 INSPIRE is a European, observational, multicenter, post-approval, open-enrollment study (EUPAS24267) evaluating the real-world effectiveness and safety of Alofisel (darvadstrocel) in patients with Crohn’s disease (CD) and complex perianal fistulas.1,2

As of September 2021, 230 patients had enrolled in the ongoing study.1 The All Treated (AT) cohort consisted of all patients in the study who received Alofisel; the Treated Per Protocol (PP) cohort consisted of all patients in the study who received Alofisel according to protocol recommendation.1 138 patients in the All Treated (AT) cohort and 120 patients in the Treated Per Protocol (PP) cohort were six-months post treatment and 66% for AT (92/138) and 58% for PP (69/120) had a six-month visit completed.1 Among them, 85% (78/92) of the AT cohort and 100% (69/69) of the PP cohort had clinical outcome data available at six-months.1 Clinical response† was observed in 73% (57/78) and 74% (51/69) of patients in the AT and PP cohorts, respectively.1 Clinical remission* was observed in 65% of patients in both cohorts (AT cohort: 51/78; PP cohort: 45/69).1

Changes in CD activity, assessed using the Harvey–Bradshaw Index, post-treatment were minimal.1 Of the 205 patients with complete treatment data, 20% (41/205) had one or more adverse event and 9.3% (19/205) had one or more serious adverse event.1 There were no reports of ectopic tissue formation and no deaths.1

“Complex perianal fistulas are a painful, disabling and often embarrassing complication of Crohn’s disease that can be extremely challenging to treat.9,10,11,12 Despite advances, many patients relapse and do not achieve fistula closure following treatment,13” said Professor Oded Zmora, Colon and Rectal Surgeon and Chair of the Department of Surgery, Shamir Medical Center, Tel Aviv, Israel, and Chair of the INSPIRE steering committee. “These promising initial results from the INSPIRE study build knowledge on Alofisel as a treatment option in this area, and I look forward to future analyses with longer follow-up times.”

“We are delighted to present the results of the first interim analysis from the real-world multicenter INSPIRE study. These results are consistent with the pivotal Phase 3 ADMIRE-CD study in terms of efficacy and safety,1” said Elisabeth Genestin, Senior Global Brand Medical Affairs Director GI Rare Disease, Takeda. “The INSPIRE study aims to include more patients, to promote a better understanding of disease presentation, patient characteristics, patterns of care and clinical outcomes in a large multicenter, heterogenous patient population and we look forward to sharing more data and insights with the community as the study progresses.2”

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.7 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%; a difference of 15.8 percentage points; 97.5% CI 0.5-31.2; P =0.021), and this was maintained over 52 weeks (56.3% vs 38.6%; a difference of 17.7 percentage points; 95% CI 4.2-31.2; P =0.01).13 Alofisel treatment was well-tolerated over 52 weeks, with a similar safety profile in the Alofisel group compared to the control group.13

* clinical remission is defined as closure despite gentle finger compression of all external openings treated with darvadstrocel that were draining at baseline

† clinical response is defined as closure despite gentle finger compression of ≥50% of external openings treated with darvadstrocel that were draining at baseline

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About Alofisel

Alofisel is a suspension of expanded allogeneic (donor-derived), adipose-derived mesenchymal stem cells (eASC) for the treatment of complex perianal fistulas in adult patients with non-active or mildly active luminal CD.3 In March 2018, Alofisel became the first allogeneic stem cell therapy to receive central marketing authorization approval in the European Union.3,14 In 2019, darvadstrocel received a Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. FDA for complex perianal fistulas in adult patients with CD.15 In September 2021, Alofisel became the first expanded human allogeneic adipose-derived mesenchymal stem cell therapy to be approved in Japan.4,16

Therapeutic Indications

Alofisel is approved in the European Union/European Economic Area, Israel, Switzerland and the United Kingdom 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.3,5,6 Alofisel should be used only after conditioning of the fistulas.3,5,6

In Japan, Alofisel is indicated for the treatment of complex perianal fistulas in patients with non-active or mildly active luminal Crohn’s disease (CD).4,16 This product is indicated for the treatment of patients who have shown an inadequate response to at least one existing medicinal treatment.4,16

Important Safety Information3

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 anesthesia is not recommended due to the unknown effect of local anesthetics on the injected cells.

The injection of any substance other than sodium chloride 9 mg/mL (0.9%) (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 darvadstrocel as this may compromise cell viability.

Alofisel is indicated for injection in the fistula tract tissue only. 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.

As Alofisel is a living stem cell therapy, it cannot be sterilized, and therefore could contain potentially infected biological material, although the risk is considered to be low and controlled in the manufacturing process. Patients should be followed up for potential signs of infection after administration.

Alofisel should only be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which Darvadstrocel is indicated.

Fertility, Pregnancy & Lactation

No data is available from the use of Alofisel in pregnant women. Alofisel 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.

Adverse reactions include: Common (≥1/100 to <1/10): anal abscess, proctalgia, anal fistula and procedural pain. Conditioning of fistulas has been associated with proctalgia and procedural pain.