cGMP was one of those milestones as per the below press release
Dec 22,2015
Amarantus Provides Update on cGMP Manufacturing Validation for the Engineered Skin Substitute (ESS) Program
SAN FRANCISCO, Dec. 22, 2015 /PRNewswire/ -- Amarantus BioScience Holdings, Inc. (OTCQB: AMBS), a biotechnology company focused on developing products for Regenerative Medicine, Neurology and Orphan Diseases, today provided an update on the status of its current manufacturing process validation for producing ESS at Lonza Walkersville, a premier contract manufacturer providing cell- and tissue-based products for clinical development. Ongoing engineering run activities are progressing successfully, and Amarantus expects to complete the necessary steps to confirm the process in January. Upon completing the validation studies, Amarantus will be ready from the operational perspective to open the planned Phase 2 clinical study for the treatment of full thickness thermal burns covering over 50% of the body. The trial is being conducted under a Collaborative Research & Development Agreement (CRADA) with the U.S. Army at the Institute for Surgical Research at Fort Sam Houston in Texas.
Milestones towards validation are as follows:
Aseptic process simulation execution and qualification of the process and personnel used in manufacturing:
Completed in November 2015
Initial engineering run whereby autologous full thickness skin from an adult human donor is produced:
Completed in December 2015
Confirmatory engineering run whereby autologous full thickness skin from an adult human donor is produced:
In progress - Expected completion in January 2016
"Validating the manufacturing process for ESS is the key operational milestone at this point on the program's path towards commercialization," said Gerald E. Commissiong, President & CEO of Amarantus. "Working with an established contract manufacturer, we will be operationally enabled to open up the 10 patient Phase 2 clinical study under our CRADA with the US Army's ISR, and we will also be in a position to initiate discussions with the FDA on trial designs for evaluating ESS in Giant Congenital Melanocytic Nevi (GCMN) and pediatric severe burn indications. We believe ESS may be eligible to achieve Rare Pediatric Disease Designation (RPDD) for both of these indications, and our regulatory team is now focused on submitting the request for RPDD for the treatment of GCMN to the U.S. FDA by the end of 2015, with a decision in the first quarter of 2016. Given that it is estimated GCMN affects a very small pediatric population, (between 8 and 80 newborns annually in the U.S), we anticipate a potentially rapid product approval pathway with the pivotal program anticipated to initiate in the second half of 2016."
The FDA defines a "rare pediatric disease" as a disease that affects fewer than 200,000 individuals in the U.S. primarily aged from birth to 18 years. Under the FDA's Rare Pediatric Disease Designation (RPDD) Priority Review Voucher (PRV) program, a sponsor who receives an approval of a new drug application (NDA) or biologics license application (BLA) for a rare pediatric disease may be eligible for a voucher, which can be redeemed to obtain expedited FDA review for any subsequent marketing application. The PRV may be sold or transferred by the recipient. The two most recent PRVs that were sold garnered a combined $595M in cash from Sanofi and Abbvie.
About Giant Congenital Melanocytic Nevus
Giant Congenital Melanocytic Nevus, a rare pediatric condition (also known as "Bathing trunk nevus," "Garment nevus," "Giant hairy nevus", and "Nevus pigmentosus et pilosus"), is defined by one or more large, darkly pigmented and sometimes hairy patches. The congenital (present at birth) melanocytic nevus appears as a circumscribed, light brown to black patch, potentially varying in consistency, covering any size surface area and any part of the body. As compared with melanocytic nevi that arise after birth, congenital melanocytic nevi are usually larger in diameter and may have excess hair, a condition called hypertrichosis. The estimated prevalence for the largest melanocytic nevi is 0.002% of births in the US. A serious risk factor for the largest CMN concerns the incidence of melanoma, which can be up to 10%. Generally, melanoma in patients with large to giant CMN occurs within the first decade of life with the greatest incidence rate before age 5 and has a high fatality rate. A second life-threatening complication of the larger forms of CMN is neurocutaneous melanocytosis (NCM), a neurological and dermatological disorder characterized by abnormal cellular aggregations within the central nervous system and the skin. The incidence of NCM ranges between 5 and 15 % in this CMN patient subset; death usually occurs within 2-3 years of diagnosis of symptomatic NCM.
About Engineered Skin Substitute (ESS)
Engineered Skin Substitute (ESS) is a tissue-engineered skin prepared from autologous (patient's own) skin cells. It is a combination of cultured epithelium with a collagen-fibroblast implant that produces a skin substitute that contains both epidermal and dermal components. This model has been shown in preclinical studies to generate a functional skin barrier. Most importantly, because ESS is composed of a patient's own cells, it is less likely to be rejected by the immune system of the patient, unlike with porcine or cadaver grafts in which immune system rejection is a possibility. ESS has been used in an investigator initiated clinical setting in over 130 human subjects, primarily pediatric patients, for the treatment of severe burns up to 95% total body surface area.
June 07,2016
Amarantus Announces cGMP Manufacturing Readiness for Its Engineered Skin Substitute (ESS) Program at Lonza Walkersville
Amarantus-sponsored training for Phase 2 severe burn trial completed with U.S. Army clinical site in late April
SAN FRANCISCO, June 7, 2016 /PRNewswire/ --
Amarantus BioScience Holdings, Inc. (OTCQB: AMBS), a biotechnology company focused on developing products for Regenerative Medicine, Neurology and Orphan Diseases, today announced that the current Good Manufacturing Practices (cGMP) manufacturing process for its Engineered Skin Substitute (ESS) program is now qualified at Lonza Walkersville, Inc., a premier contract manufacturer providing cell and tissue-based products for clinical development. ESS is a lab-grown, full-thickness skin graft made from a patient's own skin that is expanded ~100 fold in size to provide permanent wound coverage of large body surface areas, initially for use in treating life-threatening burns.
Reaching this milestone signifies that Amarantus is now positioned to supply ESS for its planned opening of the 10-patient, randomized, placebo-controlled, open-label Phase 2 clinical trial for the treatment of adult patients (ages 18-40 years old) with deep-partial and full-thickness thermal burns covering ≥50% of total body surface area (TBSA). The Company will open enrollment at the first site, the U.S. Army's Institute for Surgical Research (ISR) at Fort Sam Houston in Texas, under a Collaborative Research & Development Agreement (CRADA). Two additional civilian sites will be opened after ISR to accelerate enrollment of the study.
The Phase 2 clinical trial is designed to measure the safety and comparability of ESS with meshed split-thickness autografted skin, the current standard of care in the treatment of life-threatening severe burns. Amarantus will be reporting pre-defined data points on an ongoing basis throughout the trial on a patient-by-patient basis.
"cGMP-readiness at Lonza marks the first of several major milestones for the ESS program," said Gerald E. Commissiong, President & CEO of Amarantus. "Amarantus performed the sponsor portion of the site initiation process at ISR in late April, and the site is completing its final preparations to initiate the study. We expect the remaining items to be completed soon, at which point we will open enrollment for this breakthrough regenerative medicine cell therapy trial at the US Army's premier surgical research center."
About Engineered Skin Substitute (ESS)
Engineered Skin Substitute (ESS) is a tissue-engineered skin prepared from autologous (patient's own) skin cells. It is a combination of cultured epithelium with a collagen-fibroblast implant that produces a skin substitute that contains both epidermal and dermal components. This model has been shown in preclinical studies to generate a functional skin barrier. Most importantly, because ESS is composed of a patient's own cells, it is less likely to be rejected by the immune system of the patient, unlike with porcine or cadaver grafts in which immune system rejection is a possibility. A non-GMP version ESS has been used in investigator-initiated and compassionate-use clinical settings in over 150 human subjects, primarily pediatric patients, for the treatment of severe burns up to 95% of total body surface area. The non-GMP version has also been used in the treatment of two patients with Giant Congenital Melanocytic Nevi (GCMN). The Company is evaluating opportunities to launch a pivotal clinical study with ESS in the areas of GCMN and pediatric severe burns once experience is gained in the adult severe burn setting.
About Amarantus BioScience Holdings, Inc.
Amarantus BioScience Holdings (AMBS) is a biotechnology company developing treatments and diagnostics for diseases in the areas of neurology, regenerative medicine and orphan diseases. AMBS acquired the rights to the Engineered Skin Substitute program (ESS), a regenerative medicine-based approach for treating severe burns with full-thickness autologous skin grown in tissue culture. ESS is entering Phase 2 clinical studies under a CRADA agreement with the US Army. AMBS has development rights to eltoprazine, a Phase 2b-ready small molecule indicated for Parkinson's disease levodopa-induced dyskinesia, adult ADHD and Alzheimer's aggression, and owns the intellectual property rights to a therapeutic protein known as mesencephalic astrocyte-derived neurotrophic factor (MANF) and is developing MANF-based products as treatments for brain and ophthalmic disorders. MANF was discovered from the Company's proprietary discovery engine PhenoGuard. AMBS also received 80 million shares of Avant Diagnostics, Inc. via the sale of its wholly-owned subsidiary Amarantus Diagnostics, Inc.
