Status: approved; marketed

Organizations involved:

Modex Therapeutics Ltd. – Manuf.; R&D; Tech.; USA mark.

EpiSource S.A. – Manuf.; Europe mark.

IsoTis OrthoBiologics S.A. – Parent

Integra LifeSciences Corp. – Parent

Cross ref.: See the entry for Apligraf (#651), e.g., the Biological section, for further information about skin. See also the other cultured skin products.

Description: EpiDex is a cultured autologous (patient’s own) epidermal equivalent cultured from the patient’s hair cells. The cells used to prepare EpiDex are isolated from the outer root sheath (ORS) of anagen hair follicles plucked from the patient’s scalp. The outer root sheath contains the precursor cells for epidermal keratinocytes, which are recruited in the natural wound healing. EpiDex is multilayered, like normal human epidermis. Cryopreservation of donor cells gives physicians flexibility in planning the application date according to their requirements. Preservation of frozen cells is unlimited, and, if needed, EpiDex can be repeatedly produced from cryopreserved ORS cell stocks

EpiDex is supplied in boxes containing six discs of 0.8 cm2 area (diameter = 1 cm). EpiDex disk come with a silicone membrane backing for easier handling. Six discs of EpiDex allow the treatment of an ulcer area up to 10 cm2, assuming a wound coverage of 50%. EpiDex can be cultured and delivered six weeks after hair follicles samples are plucked. If more is needed, EpiDex discs can be manufactured from the patient’s cryopreserved cell stocks within 3 weeks. EpiDex is manufactured in compliance with GMP (Good Manufacturing Practices) and ISO 9002.

Nomenclature: skin, cultured/EpiDex [BIO]; Epidex [TR]

Biological.: The outer root sheath (ORS) contains the precursor cells for epidermal keratinocytes, which are recruited in the natural wound healing process. In vitro, ORS cells retain a high proliferative capacity irrespective of the age of the hair follicle donor. Under organotypical culture conditions, ORS cells undergo a complex differentiation process resulting within two weeks in a layered epi-dermal equivalent resembling human epidermis.

Companies.: EpiDex was developed by, is manufactured and exclusively marketed in the U.S. by Modex Therapeutics Ltd. EpiSource S.A., a subsidiary IsoTis Ortho-Bio-logics S.A. manufactures and markets Epidex for the European market. IsoTis Ortho-Bio-logics was formed in 3rd quarter 2003 by the merger of GenSci OrthoBiologics Inc. (U.S.) and IsoTis S.A. In summer 2007, Integra LifeSciences Corp. acquired IsoTis.

Approvals: Date = 20021000; first approval; Humanitarian Device Exemption (HDE)

Indications: for the treatment of recalcitrant leg ulcers

Status: EpiDex received Humanitarian Device Exemption (HDE) approval from FDA in Oct. 2002. Epidex was already marketed in Switzerland and Germany. HDE applications are exempt from the effectiveness requirements of a PMA. HDE approval allows full commercial marketing of a Humanitarian Use Device (HUD) intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or are manifested in fewer than 4,000 individuals in the U.S. per year (orphan indications:). There can be no comparable device already approved for a similar indication, and approval may be revoked when an equivalent device receives full approval. A HUD must be approved by the hospital’s Institutional Review Board (IRB) before it can be used in patients for its designated indication(s). However, the IRB does not need to review and approve individual uses. The FDA reviews the preclinical and clinical data and determines the benefits of using the product outweigh the risks (when no alternatives are available).

Trials: EpiDex has shown efficacy for treatment of recalcitrant skin ulcers previous treated with conventional split-thickness meshed grafts. The take rate of EpiDex after one week was 95%, and 57% of the ulcers showed a reduction of 80%-100% of the wound area 8 weeks after application. A considerable reduction of the wound area (>40%) was shown in 86% of ulcers 8 weeks after application.

Medical: Prior to application, the wound/ulcer is thoroughly debrided, disinfected, and rinsed. The EpiDex discs are applied one by one on the well granulating zones of the wound with sterile tweezers, placing the basal layer in direct contact with the granulating zones of the prepared ulcer bed. The discs must not overlap and should cover ~50-70% of the wound surface. The epidermal equivalent discs can be applied on wounds of any size and shape in a mosaic-like pattern. The silicone plastic membrane backing must stay on the top part of the patch and is carefully removed at the first dressing change. EpiDex involves minimal risk of pathogen transmission and transplant rejection, and is an easy and non-invasive procedure available at any age.

Market: The Average Wholesale Price (AWP) is not available (not in 2007, 2005 or 2004 Red Book).

The market/sales for this product is relatively small, much like that of other similar products.