Clinical Outcomes of Characterized Chondrocyte Implantation

Vanlauwe, Johan; J, Huylebroek; Bauwhede, Jan Van Der; Saris, Daniël B.F.; Veeckman, Geert; Bobic, Vladimir; Victor, Jan; Almqvist, Karl; Verdonk, Peter; Fortems, Yves; Lommel, Nel Van; Haazen, L.

doi:10.1177/1947603511430325

Cited by 19 publications

(12 citation statements)

References 25 publications

(35 reference statements)

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“…Eight years after the adoption of the regulation, only five ATMPs have been granted MA in the EU as of October 2015: one cell therapy, Sipuleucel-T (Provenge ® , 2013) for metastatic castrate-resistant prostate cancer ( 5 ); one gene therapy, alipogene tiparvovec (Glybera ® , 2012) for lipoprotein lipase deficiency ( 6 ); and three TEPs – autologous cartilage cells expanded ex vivo expressing specific marker proteins (Chondrocelect ® , 2009) ( 7 ), matrix applied characterised autologous cultured chondrocytes (MACI ® , 2013) for cartilage defects ( 8 ), and ex vivo expanded autologous human corneal epithelial cells containing stem cells (Holoclar ® , 2015) for severe limbal stem-cell deficiency caused by burns to the eyes ( 9 ). However, the MA for MACI ® was suspended due to the closure of the EU manufacturing site ( 10 ), and the MA for Provenge ® was withdrawn due to the bankruptcy of the MA holder Dendreon ( 11 , 12 ).…”

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confidence: 99%

Advanced therapy medicinal products: current and future perspectives

Hanna

Rémuzat

Auquier

et al. 2016

Journal of Market Access & Health Policy

113

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BackgroundAdvanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget.ObjectiveThe aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access.MethodsClinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area.ResultsThe database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations.ConclusionATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest that ATMPs may reach the market earlier than standard therapies. Targeted therapies have opened the way for new trial methodologies, from which ATMPs could benefit to get early access. ATMPs may be the next source of major impact on payers’ drug budgets.

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confidence: 99%

Advanced therapy medicinal products: current and future perspectives

Hanna

Rémuzat

Auquier

et al. 2016

Journal of Market Access & Health Policy

113

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“…5~1 0×10 5 cell/cm 2 , 通过手术植入受损部位后使用纤维蛋白胶固定细胞 [11] . europa.eu/en/medicines/human/EPAR/chondrocelect) [12] . [29] .…”

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Research progress and regulatory perspectives for stem cell-based regenerative medicine products

Lü¹,

Liu²,

Luo³

2018

Sci. Sin.-Vitae

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Advances in stem cell therapy have led to the surge of regenerative medicine products for treating severe diseases worldwide in the recent years. Stem cells are capable of self-renewal and differentiation, and regenerative medicine products are remarkably complex and varied in their manufacturing processes including methods for cell culture, induction of differentiation and engraftment. The outcomes of the clinical trials of stem cell products also bear uncertainty partly due to the disparities among patients. Therefore it is challenging for the drug administrative agencies to regulate stem cell products. In this article, we review the research progress of the licensed stem cell-based products in the USA, Europe and Japan, along with the regulations and guidance documents of FDA, EMA and PMDA. We also summarize the considerations in evaluating the Chemistry, Manufacture and Control section of stem cell product applications. We hope our effort would contribute to the establishment of science-based regulatory policy in China, and provide the insights for the development and evaluation of regenerative medicine products. regenerative medicine products, stem cell, mesenchymal stem cell, embryonic stem cell, induced pluripotent stem cell, cell therapy, drug evaluation

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“…The ChondroCelect score was developed to predict the cells ability to form stable products, such as hyaline cartilage, necessary for cartilage growth in vivo . 44 , 45 However, CC has mostly been studied using the first-generation periosteal flap ACI technique.…”

Section: Two-step Proceduresmentioning

confidence: 99%

“…This publication reported 89% of patients with a therapeutic effect after an average of 2.2 years of follow-up based on a clinical global impression for efficacy scale. 44 …”

Section: Two-step Proceduresmentioning

confidence: 99%

Advances in the Surgical Management of Articular Cartilage Defects

2012

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Objective:The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process.Design:A PubMed search was performed using the phrase “Autologous Chondrocyte Implantation” alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company websites were referenced.Results:Two-Stage Techniques: BioCart II uses a FGF2v1 culture and a fibrinogen, thrombin matrix, whereas Hyalograft-C uses a Hyaff 11 matrix. MACI uses a collagen I/III matrix. Cartipatch consists of an agarose-alginate hydrogel. Neocart uses a high-pressure bioreactor for culturing with a type I collagen matrix. ChondroCelect makes use of a gene expression analysis to predict chondrocyte proliferation and has demonstrated significant clinical improvement, but failed to show superiority to microfracture in a phase III trial. One Step Technique: CAIS is an ACI procedure where harvested cartilage is minced and implanted into a matrix for defect filling.Conclusion:As full thickness defects in articular cartilage continue to pose a challenge to treat, new methods of repair are being researched. Later generation ACI has been developed to address the prevalence of fibrocartilage with microfracture and the complications associated with the periosteal flap of first generation ACI such as periosteal hypertrophy. The procedures and products reviewed here represent advances in tissue engineering, scaffolds and autologous chondrocyte culturing that may hold promise in our quest to alter the natural history of symptomatic chondral disease.

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Clinical Outcomes of Characterized Chondrocyte Implantation

Cited by 19 publications

References 25 publications

Advanced therapy medicinal products: current and future perspectives

Advanced therapy medicinal products: current and future perspectives

Research progress and regulatory perspectives for stem cell-based regenerative medicine products

Advances in the Surgical Management of Articular Cartilage Defects

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