FDA再生醫學先進療法認定(RMAT : Regenerative Medicine Advanced Therapy) 細胞治療新策略

Mallinckrodt 人類皮膚替代物 StrataGraft 獲 RMAT 認定，加速上市時程 作者 Golden Raven 2017 年 07 月 25 日 英國製藥公司 Mallinckrodt plc 致力於為病情嚴重的患者開發先進的再生醫學療法，其研發的再生皮膚組織 StrataGraft，於 7月18日獲美國 FDA 授予再生醫學先進療法認定（Regenerative Medicine Advanced Therapy，RMAT），是首批被 RMAT 認定的產品之一，該資格提供優先審查和或加速批准的可能性。當燒燙傷深度影響到真皮層，即整個表皮和超過三分之二的真皮受到損壞，屬深部皮層燒傷（deep partial-thickness），傷口無法自行癒合而需要自體移植的植皮手術，而手術後會有供皮區及植皮區兩個傷口，後續仍需仔細照護與治療；另外，患者燒傷面積也會影響可移植的健康皮膚捐贈部位，這些皆反映出，人工皮膚等組織替代物仍是需要解決的缺口。StrataGraft 是一款具有生物活性的皮膚全皮層製品，利用纖維母細胞（dermal fibroblast）與 NIKS 表皮角質細胞（epidermal keratinocytes）為基底，可模擬人體皮膚。不同於第一代產品，StrataGraft 可縫合、固定，並可在創傷表面保持完整性，為皮膚癒合過程提供關鍵的屏障功能。2016 年底 Mallinckrodt 已開展一項開放、隨機、多國多中心的臨床 3 期試驗，以評估 StrataGraft 對於 deep partial-thickness傷口，是否具刺激自體皮膚組織再生能力及安全性。該試驗對象為皮膚燒燙傷佔總體皮膚表面積 3%~49%、且因其完整皮層受熱損傷，經臨床指示需進行切除或自體皮膚移植的患者，於試驗進行後 3 個月將測量試驗結果，包含：以 StrataGraft 移植前後的治療部位面積百分比，並與自體皮膚移植進行對照。經 StrataGraft 治療後，傷口可自行完全癒合的受試者比例。美國生物醫學先進研究與開發局（United States Biomedical Advanced Research and Development Authority，BARDA）已與 Mallinckrodt 簽立 5 年合約，合作執行 StrataGraft的 3期臨床試驗與開發。有 BARDA 支持，加上美國國防部的生物防禦計畫（Project Bioshield）的補助，兩項目共提供超過 7,780 萬美元，將用於完成3期臨床與後續項目推動。美國 FDA 基於《21 世紀醫療法案》（21st Century Cures Act）提供 RMAT 的認定，旨在加速用於嚴重疾病再生醫學療法的開發及查驗登記進程。要獲得 RMAT 資格認定，必須在初步的臨床試驗結果，便可證明藥物對於疾病治療或是未滿足的醫療需求有積極的結果。RMAT 須與 IND（新藥臨床試驗）或是對現有 IND 進行修正時，一同提交申請，FDA 不會要求必須提出主要數據，但必須說明包括對適應症的任何可用療法的簡要描述、研究設計、試驗族群和所採計的試驗終點，及對研究結果和統計分析的描述。截至今年 5 月，FDA 已收到 17 項 RMAT 認定申請，其中已有 4 項獲得認定資格。TrendForce 分析師指出，再生醫學發展是醫療領域主要趨勢之一，若獲得 RMAT 資格認定的療法，最終被證明安全有效，通過審核後能確實應用於臨床治療，RMAT 認定的法規路徑將對再生醫學領域產生積極的影響。對於加速細胞治療或其他再生醫學等先進療法的審核，繼日本法規大幅開放之後，美國 RMAT 資格認定也值得學習，反觀台灣於再生醫學的法規環境，雖貌似有逐步開放的趨勢，但仍缺乏明確管理規範，監管制度在一定程度上也限制再生醫學研發的進程，這也導致一些掌握先進技術的公司，正透過國際合作，選擇法規先進環境，例如日本等，使台灣逐步喪失在全球再生醫學佔有一席之地的機會。

U.S. FDA Designates Mallinckrodt's StrataGraft® as Regenerative Medicine Advanced Therapy  Jul 18, 2017, 07:00 ET  STAINES-UPON-THAMES, United Kingdom, July 18, 2017 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today announced that StrataGraft® regenerative skin tissue is among the first products to be designated as a Regenerative Medicine Advanced Therapy (RMAT) by the U.S. Food and Drug Administration (FDA) under the provisions of the 21st Century Cures Act. The company's investigational, tissue-based therapy is currently under evaluation in a Phase 3 trial to assess its efficacy and safety in the promotion of autologous skin regeneration of complex skin defects due to thermal burns that contain intact dermal elements (also known as deep partial thickness burns).   Passed in 2016, the 21st Century Cures Act allows the FDA to grant accelerated review approval to products that meet certain criteria.  A product may receive an RMAT designation if the drug is1: defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products; intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and preliminary clinical evidence indicates the drug has the potential to address unmet medical needs for such disease or condition. "We are very pleased the FDA has determined StrataGraft meets the criteria for RMAT designation, as this offers the possibility of priority review and/or accelerated approval," said Steven Romano, M.D., Chief Scientific Officer and Executive Vice President, Mallinckrodt. "This provides the potential to bring a much-needed therapeutic option to patients even sooner than originally planned." The RMAT designation allows for earlier and increased interactions with the FDA, including discussions of whether priority review and/or accelerated approval would be appropriate based on surrogate or intermediate endpoints that would be reasonably likely to predict long-term clinical benefit; or reliance upon data obtained from a meaningful number of sites. Once approved, when appropriate, the FDA can require various post-approval commitments.2 "RMAT designation of StrataGraft skin tissue speaks to the strength of the clinical data generated during the prior clinical study," said Lynn-Allen Hoffman, Senior Vice President, Regenerative Medicine, Mallinckrodt. "Mallinckrodt is committed to developing advanced regenerative medicine therapies such as StrataGraft for patients with serious conditions." Find more information about the ongoing StrataGraft Phase 3 clinical trial here on the ClinicalTrials.gov website. Prior clinical study details can be seen here. This project has been funded in part with federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Contracts No. HHSO100201300017C and HHSO100201500027C. BARDA is supporting the development of StrataGraft tissue as a potential medical countermeasure for large-scale burn incidents.

About Serious Thermal Burns Containing Intact Dermal Elements Deep partial-thickness burns are complex skin injuries where the entire epidermis and more than two thirds of the dermis is destroyed. The treatment for severe complex skin wounds with substantial loss of the dermis such as deep partial-thickness burns is the surgical harvesting of a sheet of healthy skin from an uninjured site on the patient and transplantation of this autologous skin graft to the injury once the wound is ready to receive an autograft. While this process can be effective in providing closure of the original wound, it has significant limitations related to the donor site wounds created during surgical removal of autologous skin tissue for grafting. These donor site wounds are extremely painful, prone to infection and scarring, and can themselves convert to full-thickness wounds that must then be managed to promote healing. In addition, the amount of healthy skin available for harvesting is frequently limited in large burns, necessitating sequential re-harvesting of available donor sites. As a result, there is an urgent need for alternatives to donor site harvesting for treatment of severe burns and other complex skin defects.

 

About StrataGraft Regenerative Skin Tissue StrataGraft regenerative skin tissue is a viable, full-thickness product being developed for severe burns and other complex skin defects that is not yet approved by the U.S. Food and Drug Administration. It was designed to mimic natural human skin, with both dermal and fully differentiated epidermal layers. Unlike first generation products, StrataGraft skin tissue can be sutured, stapled or secured with an adhesive and remains intact in the wound bed, providing critical barrier functionality during the wound healing process. StrataGraft skin tissue is produced using NIKS® cells grown in accordance with Good Manufacturing Practice. Because the continuous NIKS skin cell line has been thoroughly characterized, StrataGraft tissue is virus-free, non-tumorigenic, and offers batch-to-batch genetic consistency.

ABOUT MALLINCKRODT Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical products and therapies. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; and analgesics and hemostasis products. The company's core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company's Specialty Brands segment includes branded medicines and its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing. To learn more about Mallinckrodt, visit www.mallinckrodt.com. Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.