Spherox (spheroids of human autologous matrix-associated chondrocytes) / Haemo Pharma, ReLive Biotech - LARVOL DELTA

Microfractures, autologous matrix-induced chondrogenesis, osteochondral autograft transplantation and autologous chondrocyte implantation for knee chondral defects: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, EFORT Open Rev) - "The lower failure and reoperation rates with chondrospheres must be interpreted with caution since adverse event data was heterogenous among trials. The standardization of the efficacy and safety outcome measures for future trials on knee cartilage repair and regeneration is necessary."

Journal • Retrospective data • Review • Musculoskeletal Diseases • Orthopedics • Transplantation

Cartilage-Specific Gene Expression and Extracellular Matrix Deposition in the Course of Mesenchymal Stromal Cell Chondrogenic Differentiation in 3D Spheroid Culture. (PubMed, Int J Mol Sci) - "These results confirm that the potential of Wharton's jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs."

Journal • Stroma • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology • TGFB1

Hydrogel-based and spheroid-based autologous chondrocyte implantation of the knee show similar 2-year functional outcomes: An analysis based on the German Cartilage Registry (KnorpelRegister DGOU). (PubMed, Knee Surg Sports Traumatol Arthrosc) - "The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively; however, the clinical relevance of this benefit is yet to be proven."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study. (PubMed, Knee Surg Sports Traumatol Arthrosc) - "Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI."

Clinical data • Journal • Observational data • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology • Transplantation

Human induced pluripotent stem cell line from fibroblasts (HEBHMUi015-A) and chondrogenic differentiation. (PubMed, Stem Cell Res) - "And the iPSCs were further differentiated to chondrosphere in vivo. The models could be used to test multiple differentiation protocols and also as a control for screening drugs and studying cartilage related disease."

Journal • Preclinical • KLF4 • MYC • SOX2

Evaluating the Budget Impact of NOVOCART Inject Plus (Ninject) for Symptomatic Knee Cartilage Defects in the NHS (ISPOR-EU 2023) - P3 | "The analysis of net budget impact compared Ninject with the current treatments, microfracture (MF), and Spherox... The introduction of Ninject in the NHS is not expected to have a significant resource impact, with an estimated annual budget impact of less than £1.3 million for NHS England. This is because Ninject is priced similarly to current standard treatments and will replace current treatments in certain patients. Furthermore, the affected population size is relatively small, with fewer than 10,000 patients affected per year."

HEOR • Musculoskeletal Diseases

A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis. (PubMed, Front Bioeng Biotechnol) - "Then, the spheroids were assembled into chondrospheres using a bottom-up strategy, to obtain an in vitro cytokines-induced OA model...Our approach provides a faithful reproduction of early-stage osteoarthritis, demonstrating the ability of obtaining different disease severity by tuning the concentration of OA-related cytokines. Given the advantages in easy access and more reproducible performance, Y201-C may represent a more favourable source of chondrocytes for establishing more standardized protocols to obtain OA models."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • TNFA

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture. (PubMed, J Med Econ) - "This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox."

Cost effectiveness • HEOR • Journal • Musculoskeletal Diseases

Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc. (PubMed, Front Bioeng Biotechnol) - "Anti-inflammatory and anabolic drugs (amiloride, celecoxib, metformin, IL-1Ra, GDF-5) were used for pre-conditioning of NC/NCS...In particular, we showed that NC in spheroidal organization as compared to NC cell suspension exhibited superior regenerative performance and that IL-1Ra pre-conditioning of NCS could further improve their ability to counteract inflammation/catabolism and support new matrix production within harsh degenerative disc disease microenvironment. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of IVD repair."

Journal • Immunology • Inflammation • Musculoskeletal Diseases • CASP3 • CXCL8 • IL1R1 • IL6 • MMP13 • MMP3

ReLive Completes Cross-Border M&A of Regenerative Medicine and Shanghai Biomedical Fund Leads Series A Financing [Google translation] (36Kr) - "36 Krypton learned that ReLive Biotechnologies Ltd...a tissue engineering and regenerative medicine company facing the global market, has officially announced that it has completed the acquisition of the entire assets of Co.Don AG...a listed biotechnology company in Germany. Work, and included Spherox/Chondrosphere, one of the only cartilage repair cell therapy products approved by European and American regulatory agencies in the world."

M&A • Back Pain • CNS Disorders • Pain

The Use of Patient Reported Outcomes in Aiding the Reimbursement Decisions of Advanced Medicinal Therapy Products (ISPOR-EU 2022) - "In one example, HAS considered the use of the PROs in the assessment of Spherox® as subjective and did not reward reimbursement... The inclusion and classification of PROs in HTA assessments of ATMPs varied between countries. If PROs will play an important role in measuring the value of these therapies, there is a need to use both generic and disease-specific PROs across all ATMPs – and to compare the PRO evidence to meaningful comparators."

Clinical • Patient reported outcomes • Reimbursement • Gene Therapies

Acquired a German listed company, the regenerative medicine company "ReLive" accelerates its global layout [Google translation] (36Kr) - "On the evening of October 17, German time, ReLive Biotechnologies Ltd...announced that it has officially signed an agreement to fully acquire the main assets of Co.Don AG...a German listed company. The acquisition will close in November 2022....Its core product, Spherox, is the only cell therapy product officially approved in Europe for articular cartilage repair and regeneration . One of the recycled products."

M&A • Back Pain • CNS Disorders • Pain

CO.DON AG: The European Commission grants an indefinite extension of the EU-wide approval of the drug Spherox [Google translation] (pressetext) - "The European Commission has granted the unlimited extension of the EU-wide approval for the drug Spherox without additional conditions. In addition, Spherox will be removed from the list of drugs with additional surveillance measures, in which every drug of the class ATMP (Advanced Therapy Medicinal Products) will be included after approval. With the grant, the European Commission follows the recommendation of the Committee for Human Medicinal Products (official abbreviation: CHMP) of the European Medicines Agency (EMA) made in February."

European regulatory • Back Pain • CNS Disorders • Pain

CO.DON AG: Spherox is included in the list of reimbursable medicines in Belgium (pressetext) - "As of April 1 of the current year, the product offered by CO.DON AG will be included in the list of reimbursable medicines in Belgium. This was preceded by a positive cost-benefit assessment by the Belgian Institute for Health and Disability Insurance INAMI, which was endorsed by the responsible ministry."

Reimbursement • Back Pain • CNS Disorders • Pain

CO.DON AG: CO.DON AG and JOINT OPERATIONS (UK) LLP sign contract for the distribution of Spherox in United Kingdom (Market Screener) - "CO.DON AG and JOINT OPERATIONS (UK) LLP signed an exclusive agreement to distribute the EU-authorised, cell-based medicinal product Spherox in the United Kingdom, including Scotland, Wales and Northern Ireland. The contract is initially for three years and defines minimum order quantities. CO.DON AG will support JOINT OPERATIONS (UK) LLP throughout the entire distribution period and retains defined responsibilities."

Licensing / partnership • Back Pain • CNS Disorders • Pain

CO.DON AG: EU-wide approval of the drug Spherox recommended for unlimited validity [Google translation] (CO.DON Press Release) - "CO.DON AG has received the final assessment from the European Medicines Agency’s Committee for Medicinal Products for Human Use for its pharmaceutical product Spherox, which has central EU marketing authorisation. The Committee recommends renewing the marketing authorisation for the product for an unlimited period and without any additional conditions. It further recommends removing Spherox from the list of medicines under additional monitoring five years after its initial authorisation."

European regulatory • Back Pain • CNS Disorders • Pain

Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review. (PubMed, Int J Mol Sci) - "The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients."

Clinical • Journal • Review • Oncology

Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair. (PubMed, Cartilage) - "Clinical applications of chondrocytes with matrix science include Reveille Cartilage Processor, Cartiform, and ACI with Spherox (which was recently recommended for the treatment of grade III or IV articular cartilage defects over 2 cm by the National Institute of Health and Care Excellence [NICE] in the United Kingdom). The current article presents a comprehensive overview of both the basic science and clinical results of these next-generation cartilage repair techniques by focusing specifically on the scientific evolution in each category as it pertains with underlying chondrocytes with matrix theory."

Clinical • Journal • Developmental Disorders • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

[VIRTUAL] Market Access Landscape for Advanced Therapy Medicinal Products in the EU-5 (ISPOR-EU 2020) - "The reimbursement and pricing vary between countries as outlined below: France: 7/11 ATMPs were assessed (vs 6/10 in 2019) and 6 (vs 5 in 2019) obtained a positive reimbursement decision: three (vs 0 last year) have a public price (Yescarta, Kymriah, Alofisel)...Italy: 5/11 drugs (vs 2/10 in 2019) are reimbursed to date (Strimvelis, Holoclar, Zalmoxis, Kymriah, Yescarta)...UK: 7/11 drugs (vs 6/10 in 2019) are approved by NICE: Spherox via STA with the two CAR-Ts included in the CDF. Three technologies (Holoclar, Imlygic and Luxturna) were recommended with a simple discount Patient Access Scheme. Two ATMPs, Zynteglo and Zolgensma are currently being evaluated by NICE. CONCLUSIONS Most ATMPs are granted patient access in EU5 even though HTA bodies have imposed monitoring requirements to ensure the value reflects the price."

Three-dimensional, Scaffold-Free, Autologous Chondrocyte Transplantation: A Systematic Review. (PubMed, Orthop J Sports Med) - "ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach."

Journal • Review • Orthopedics • Pain • Transplantation

Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. (PubMed, Pharmacoeconomics) - "Chondrosphere (Spherox) is a form of autologous chondrocyte implantation (ACI)...The company revised cost-effectiveness estimates for Chondrosphere versus MF and for Chondrosphere versus matrix-applied characterised autologous cultured chondrocyte implant (MACI) were £4360 and around £18,000 per quality-adjusted life year gained, respectively. NICE recommended ACI using Chondrosphere for treating symptomatic articular cartilage defects of the femoral condyle and patella of the knee in adults only if certain requirements were met."

Journal • Review

THE REIMBURSEMENT STATUS OF ADVANCED THERAPY MEDICINAL PRODUCTS IN EUROPE (ISPOR-EU 2019) - "RESULTS : Fourteen ATMPs were approved in Europe: Chondrocelect®, Glybera®, MACI®, Provenge®, Holoclar®, Imlygic®, Strimvelis®, Zalmoxis®, Spherox®, Alofisel®, Kymriah®, Yescarta®, Luxturna® and Zynteglo®. Conditional reimbursement is increasingly considered as useful policy to mitigate uncertainty. It allows gathering long-term evidence without delaying patient access to ATMPs."

Reimbursement

INNOVATIVE ATMPS- MARKET ACCESS AND REIMBURSEMENT DECISIONS IN THE EU5- AVAILABILITY OR NOT, THAT IS THE QUESTION... (ISPOR-EU 2019) - "OBJECTIVES: Since 2015, innovative ATMPs (Alofisel, Kymriah, Holoclar, Imlygic, Spherox, Strimvelis, Yescarta, Zalmoxis, Luxturna and Zynteglo) have been reached market authorization through the EMA. There is no difference in market access processes for ATMP therapies in comparison to standard pathways in Europe. Innovative and sustainable pricing schemes are under discussions within all payers in Europe."

Reimbursement

Matrix-Associated Autologous Chondrocyte Implantation Is an Effective Treatment at Midterm Follow-up in Adolescents and Young Adults. (PubMed, Orthop J Sports Med) - "...Third-generation matrix-associated ACI (MACI) using spheroids (co.don chondrosphere/Spherox) is an effective and safe treatment for articular cartilage defects in adolescents aged 15 to 17 years, with outcomes comparable with those for young adults aged 18 to 34 years...Third-generation MACI using spheroids is a safe and effective treatment for large cartilage defects of the knee in adolescents at midterm follow-up. Outcomes are comparable with those for young adults after ACI."

Clinical • Journal