CMS Statement on Proposed Local Coverage Determination (LCD) for Skin Substitute Grafts/Cellular and Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers
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BALTIMORE, MD, April 25, 2024. The FDA/CMS announced a proposal regarding the reimbursement Q codes and related 510k for Medicare Administrative Contractors (MACs) that supply skin substitutes also referred to as CTPs (cellular and/or tissue-based products) or CAMPs (cellular, acellular, and matrix‑like products) valued at $2.4Bn for the US market
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Skin substitutes are considered advanced wound care products and have benefited from very positive reimbursement codes. The proposal set out new rules that cover all existing products (211 products) regarding the burden of poof that they each are required attain in order to maintain their reimbursement. This has led to only 15 products remaining on the reimbursed list.
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All other products that have not demonstrated a net positive outcome, specifically, wound closure attributable to the individual product(s), in a well-defined patient population, proven in clinical trials with a meaningful degree of certainty, will be removed.
3K3A-APC is Efficacious and Safe in Wound-Healing Models
SYDNEY, Australia, January 3, 2024. Researchers from the Kolling Institute for Medical Research in Sydney, Australia have found that 3K3A-APC is efficacious and safe in wound-healing models in mice and pigs. These results were published online today in the journal Wound Repair and Regeneration.
Various preclinical and clinical studies previously demonstrated the robust wound healing capacity of the natural anticoagulant activated Protein C (APC). A bioengineered APC variant optimized for human therapeutic use, designated 3K3A-APC, retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. The new results published today from a research team led by Prof. Chris Jackson found that topical 3K3A-APC treatment accelerated mouse wound healing and was superior to APC in that model. 3K3A-APC also advanced healing in a wound-healing model in pigs, whose skin is very similar to human skin. The macroscopic wound healing correlated with histological findings of greater collagen maturity, suggesting more advanced remodelling. In a non-interference arm of the same study in pigs, no evidence was found of any systemic side effects. The researchers note that these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.
The full citation for the publication is:
Zhao R, Xue M, Lin H, Smith M, Liang H, Weiler H, Griffin JH, Jackson CJ. A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models. Wound Repair Regen. 2024 Jan-Feb;32(1):90-103. doi: 10.1111/wrr.13148. Epub 2024 Jan 3. PMID: 38155595.
3K3A-APC Protects Mice from Allergic Contact Dermatitis
SYDNEY, Australia, January 19, 2024. An international team of researchers in the United States and Australia have found that 3K3A-APC protects mice from allergic contact dermatitis in a contact hypersensitivity model. These results were published online today in the International Journal of Molecular Sciences.
Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. The new results published today came from a a contact hypersensitivity (CHS) model of allergic contact dermatitis in wild-type mice and EPCR-deficient (knock-out) mice. Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (APC). It mediates the anti-inflammatory and barrier-protective functions of APC through the cleavage of protease-activated receptor (PAR)1/2. While both types of mice exhibited clinical and histological signs of allergic contact dermatitis, the mice lacking the EPCR gene exhibited worse symptoms. 3K3A-APC could reduce the severity of allergic contact dermatitis both wild-type mice and EPCR-deficient mice. These results provide direct evidence that EPCR deficiency can exacerbate CHS and that the administration of 3K3A-APC can help reduce its severity. These results suggest that EPCR plays a crucial role in protecting against skin inflammation and the researchers note that 3K3A-APC could be a valuable therapeutic option for allergic contact dermatitis and other inflammatory skin disorders as well.
The full citation for the publication is:
Xue, M.; Jackson, C.J.; Lin, H.; Zhao, R.; Liang, H.P.H.; Weiler, H.; Griffin, J.H.; March, L. Endothelial Protein C Receptor and 3K3A-Activated Protein C Protect Mice from Allergic Contact Dermatitis in a Contact Hypersensitivity Model. Int. J. Mol. Sci. 2024, 25, 1255. https://doi.org/10.3390/ijms25021255
Early Protein C Activation is Reflective of Burn Injury Severity
SYDNEY, Australia March 20, 2021 — Researchers from the Kolling Institute for Medical Research and the Royal North Shore Hospital in Sydney, Australia have found that early activation of Protein C (PC) following a burn is associated with more severe burns, and this activation leads to depletion of Protein C and poorer clinical outcomes. These results were published online today in the journal Burns.
Navigating the complexities of a severe burn injury is a challenging endeavor where the natural course of some patients can be difficult to predict. Having a biomarker to help doctors assess these patients would be of great use. Activated Protein C (APC) is an established cytoprotective agent that was hypothesized to play a major role in the body’s response to a burn.The researchers studied 86 patients presenting with major burns, taking blood samples over three weeks to look at PC, (APC), and a variety of markers of inflammation. Their temporal trends were analyzed alongside clinical factors including burn size, burn depth, presence and inhalational injury. In these burn patients, APC was depressed relative to PC, reaching its lowest levels on day 3. This early disturbance in the PC system was more pronounced in patients with more severe burns, and critically low levels of APC were associated with greater inflammatory burden as measured by increases in the levels of several markers of inflammation. The researchers conclude that APC and PC may be useful as early diagnostic and prognostic biomarkers for burns, and may have therapeutic potential in severe burn injuries.
The full citation for the publication is:
Zhao R, Lang TC, Kim A, Wijewardena A, Vandervord J, McGrath R, Fulcher G, Xue M, Jackson C. Early protein C activation is reflective of burn injury severity and plays a critical role in inflammatory burden and patient outcomes. Burns. 2022 Feb;48(1):91-103. doi 10.1016/j.burns.2021.03.004. Epub 2021 Mar 20. PMID: 34175158.