Sakracy

Product description/product information

Sakracy is a cultured autologous oral mucosal epithelial cell sheet consisted with patient’s own oral mucosal epithelial cells, which are isolated from the patient’s tissue and then seeded and cultured on an amniotic membrane substrate prepared from human allogeneic amniotic membrane. Sakracy is transplanted onto the exposed cornea or sclera of a patient with ocular surface diseases accompanying limbal stem cell deficiency, such as adhesion and conjunctival fornix shortening, after adhesion release or scar tissue removal so that the oral mucosal epithelial cells will be engrafted and epithelialized, leading to the repair of any ocular surface abnormality.

Brand name

Product name: Sakracy
Nonproprietary name: Human (autologous) oral mucosa-derived epithelial cell sheet using human amniotic membrane substrate
Brand name: Sakracy

Marketing Authorization Holder

Hirosaki Lifescience Innovation, Inc.

JAN code

Oral mucosal tissue transport set: 4595124264026
Culture autologous oral mucosal epithelial cell sheet package: 4595124264019

Approval No.

30400FZX00001000

Date of approval

January 2022

Reimbursement listing

September 2022

Indication or performance

Alleviation of adhesion on the ocular surface accompanying limbal stem cell deficiency

Related precautions

  • As Sakracy is not intended to be used for the treatment of etiologies of limbal stem cell deficiency, it should be used after the management of causative etiologies of limbal stem cell deficiency.
  • Eligible patients should be selected with a full understanding of the description of clinical studies for the characteristics (e.g., degree of adhesion) of patients included in clinical studies and of the efficacy and safety of Sakracy.

Product composition and dosage form

Oral mucosal tissue transport set

Oral mucosal tissue transport set

Cultured autologous oral mucosal epithelial cell sheet package

Cultured autologous oral mucosal epithelial cell sheet package

H&E staining image of multiple layers of oral mucosal epithelial cells on an amniotic membrane substrate

H&E staining image of multiple layers of oral mucosal epithelial cells on an amniotic membrane substrate

Ref. Nakamura, T et al. Br J Opthalmol 2004

History of Development

Dr. Shigeru Kinoshita

Dr. Shigeru Kinoshita

Emeritus Professor, Kyoto Prefectural University of Medicine
Professor, Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine (since 2015)
Honorary member, Japan Cornea Society
Director, Keratoplasty Society of Japan (FY2023)

Dr. Chie Sotozono

Dr. Chie Sotozono

Professor, Department of Ophthalmology, Kyoto Prefectural University of Medicine (since 2015)
Executive Director, Japanese Ophthalmological Society (from 2023 to 2025)
Director, Japan Cornea Society (from 2023 to 2025)

Research on cultured autologous oral mucosal epithelial cell sheets has been conducted by Dr. Shigeru Kinoshita and colleagues from the Department of Ophthalmology, Kyoto Prefectural University of Medicine. A clinical investigation was started in 2002, and a total of 72 patients underwent transplantation as of 2008. A retrospective analysis of these patients confirmed the efficacy of cultured autologous oral mucosal epithelial cell sheets.

Subsequently, a clinical investigation under the Advanced Medical Care B program (from July 2014 to September 2017) supported by Health, Labour, and Welfare Sciences Research Grants was conducted, and an investigator-initiated trial in subjects with severe stem cell deficiencies for the release of adhesions on the ocular surface titled “A multicenter, single-arm, phase 3 study of transplantation of cultured autologous oral mucosal epithelial sheets to supply mucosal epithelium in patients with refractory ocular surface diseases” (from October 2018 to September 2019) was conducted by Dr. Chie Sotozono, Department of Ophthalmology, Kyoto Prefectural University of Medicine, with support for the production by FBRI.

To enable the provision of a new treatment option for patients with severe limbal stem cell deficiencies, our company submitted a marketing authorization application to the Ministry of Health, Labour and Welfare based on the results from the investigator-initiated trial and received approval for Sakracy on January 20, 2022, with the product beginning to be covered by insurance on September 1, 2022.

“Sakura” (cherry blossoms) is a common symbol between Hirosaki City, in which our company is founded, and Kyoto City, which is the development base for the product. This product was named “Sakracy” in the hope that patients will experience visual acuity improvement and can view and enjoy sakura (cherry blossoms).

Department of Ophthalmology, Kyoto Prefectural University of Medicine

Target patients

Schemes

Clinical trial

Target patients

Limbal stem cell deficiency (LSCD) is one of the reason that is featured severe ocular surface disease, including conjunctivalization of the cornea, symblepharon, fornix-shortening, and persistent epithelial defect.

Such a loss of limbal stem cells and dispopulation of corneal epithelium often occur due to several syndromes and accidents.

Underlying disease

  • Autoimmune diseases*
  • Chemical burn
  • Recurrent pterygium
  • Ocular tumor
  • Aniridia

Ocular surface disease

  • Limbal stem cell deficiency
  • Corneal epithelium deficiency

Condition

  • Severe adhesion
  • Symblepharon
  • Loss of vision

*SJS (Stevens-Johnson syndrome), OCP (Ocular cicatricial pemphigoid), GVHD (Graft versus host disease), etc

COMET (cultivated oral mucosal epithelial transplantation) is one of most effective option, the durability is significantly expected.

“Sakracy” is a product for COMET using amnion membrane as a substrate matrix. It is known that amnion membrane matrix also have a function of anti-inflammation on ocular surface.

Case of COMET using amnion membrane matrix

Case of COMET using amnion membrane matrix

Sotozono C, et al. Visual improvement after cultivated oral mucosal epithelial transplantation Ophthalmology 120, 193-200 (2013)
Komai S, et al. Long-term outcome of cultivated oral mucosal epithelial transplantation for fornix reconstruction in chronic cicatrising diseases
Br J Ophthalmol 106, 1355-1362 (2022)

Treatment scheme

口腔粘膜上皮細胞シートの製造と移植

*Sakracy can be cut into an appropriate shape to be transplanted into the cornea and other sites.

  • (1)

    The oral mucosal tissue is collected from the patient. (The oral environment should be prepared by prior dental care and other means as necessary. Adequate disinfection should be performed on the day of collection.)

  • (2)

    The collected tissue is transported to the manufacturing site and cultured on an amniotic membrane substrate (for two weeks).

  • (3)

    After removal of adhesions on the ocular surface, Sakracy is transplanted. (Post-transplant management with immunosuppressants should be performed as appropriate.)

Post-transplant management

The following treatments are provided where necessary:

  • (1)

    Use of a therapeutic contact lens.

  • (2)

    For patients with a primary disease other than ocular cicatricial pemphigoid, oral cyclosporine 2 to 3 mg/kg daily from the day after transplantation with dose adjustment according to the symptoms.

  • (3)

    For patients with a primary disease of ocular cicatricial pemphigoid, oral cyclosporine 2 to 3 mg/kg daily and oral cyclophosphamide 50 mg (on the anhydrous basis) once daily from the day after transplantation with dose adjustment according to the symptoms.

Clinical experience

A Japanese phase 3 investigator-initiated trial (Study title: A multicenter, single-arm, phase 3 study of transplantation of cultured autologous oral mucosal epithelial sheets to supply mucosal epithelium in patients with refractory ocular surface diseases) was conducted from October 2018 to September 2019.

Objective

To evaluate the efficacy and safety of oral mucosal epithelial cell sheets to supply the mucosal epithelium in subjects with refractory ocular surface diseases accompanying a severe stem cell deficiency who had the causative etiology of Stevens-Johnson syndrome, ocular pemphigoid, or thermal/chemical injuries and had severe adhesion* on the ocular surface.

Number of subjects

Seven subjects

Study method

The oral mucosal tissue was collected from subjects three weeks before transplantation. A cultured oral mucosal epithelial sheet was prepared and transplanted. At 24 weeks after transplantation, an evaluation was performed. (Subjects were followed up in hospital for approximately two weeks after transplantation.)

Eligibility criteria

Patients with refractory ocular surface diseases that are likely to result in a poor prognosis by corneal epithelium transplantation or unlikely to resolve with amniotic membrane transplantation alone. More specifically, patients with Stevens-Johnson syndrome, ocular pemphigoid, or thermal/chemical injuries and severe adhesion* on the ocular surface. *Severe adhesion: Adhesion score ≥ 4.

Total adhesion score

Defiend as the sum of the symblepharon and fornix-shortening scores

Total adhesion score

Results

Primary outcome

The mean of total adhesion score (central) changing by pre-transplantation to 24 weeks later significantly decreased; -2.6 (95%CI: -4.5 ~ -0.7), one sample t-test.

Primary outcome

The score changing of individual case are shown as below table.
The combination surgery of amniotic membrane transplantation is performed in all case.

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