Horizon Scanning Centre November Spheroids of human autologous matrix-associated chondrocytes (Chondrosphere) for articular cartilage defects

Transcription

1 Horizon Scanning Centre November 2014 Spheroids of human autologous matrix-associated chondrocytes (Chondrosphere) for articular cartilage defects SUMMARY NIHR HSC ID: 8515 This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. Spheroids of human autologous matrix-associated chondrocytes are intended to be used as therapy for articular cartilage defects. If licensed, this technology will provide an additional treatment option for this patient group. Spheroids of human autologous matrix-associated chondrocytes are formed from the patient s own undamaged articular condyles. Chondrocytes are harvested from healthy articular cartilage, cultivated for 8-10 weeks in vitro, and condensed into spheroids (chondrospheres). The 3-dimensional spheroids are then transplanted into the defect. Spheroids of human autologous matrix-associated chondrocytes are licensed in Germany for the treatment of articular cartilage defects of the knee, hip, shoulder, elbow and ankle. Articular cartilage damage in the knee may be caused by acute injury, often as a result of a sporting activity. Long-term, damage to the articular cartilage can lead to osteoarthritis, and in some cases, knee replacement with an artificial joint is required. There are no reliable estimates of the prevalence of symptomatic articular cartilage defects of the knee, although an estimated 10,000 people have cartilage damage serious enough to require treatment in the UK every year. The number of people with symptomatic cartilage defects suitable for autologous chondrocyte implantation is estimated to be between 200 and 500 per year in the UK. Current treatment options include analgesics for relief of symptoms, knee lavage, and procedures to re-establish the articular surface, such as marrow stimulation techniques, mosaicplasty, and autologous chondrocyte implantation. Spheroids of human autologous matrix-associated chondrocytes are currently in phase III clinical trials comparing their effect on the Knee Injury and Osteoarthritis Outcome Score (KOOS) against microfracture therapy. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Centre, University of Birmingham nihrhsc@contacts.bham.ac.uk Web:

2 TARGET GROUP Patients with articular cartilage defects, initially of the knee, but the company report that the anticipated licence may potentially also include the hip, shoulder, elbow and ankle. TECHNOLOGY DESCRIPTION Spheroids of human autologous matrix-associated chondrocytes (Chondrosphere; ACT3D- CS) are formed from the patient s own undamaged articular condyles. Chondrocytes are harvested from healthy articular cartilage, cultivated for 8-10 weeks in vitro, and condensed into spheroids (chondrospheres). The 3-dimensional spheroids are then transplanted into the defect. In clinical trials 1, the recommended dose of spheroids of human autologous matrixassociated chondrocytes was spheroids/cm 2. Spheroids of human autologous matrix-associated chondrocytes are licensed in Germany for the treatment of articular cartilage defects of the knee, hip, shoulder, elbow and ankle 2. INNOVATION and/or ADVANTAGES If licensed, spheroids of human autologous matrix-associated chondrocytes for articular cartilage defects will provide an additional treatment option for this patient group. DEVELOPER Co.don. AVAILABILITY, LAUNCH OR MARKETING The company submitted a Marketing Authorisation Application to the EMA in Q PATIENT GROUP BACKGROUND Articular cartilage refers to hyaline cartilage on the articular surfaces of bone 3, which provides a smooth and resilient surface, allowing virtually frictionless movement within the knee joint 4. Cartilage has no blood vessels and therefore has very limited ability to repair itself 5. Articular cartilage damage in the knee can be caused by acute injury, often as a result of a sporting activity, or it may arise without obvious trauma in individuals with defective cartilage 3. Damage to the articular cartilage is associated with symptoms such as knee pain, knee swelling, knee locking and giving way of the knee joint 3. Long-term, this can lead to osteoarthritis, and in some cases a knee replacement with an artificial joint is required 5. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: The National Service Framework for long-term conditions

3 NHS England. 2013/14 NHS Standard Contract for specialised orthopaedics. D10/S/a. CLINICAL NEED and BURDEN OF DISEASE There are no reliable estimates of the prevalence of symptomatic articular cartilage defects of the knee, although an estimated 10,000 people have cartilage damage serious enough to require treatment in the UK every year 3. The number of people with symptomatic cartilage defects suitable for autologous chondrocyte implantation is estimated to be between 200 and 500 people per year in the UK 3. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance NICE technology appraisal in development. Autologous chondrocyte implantation for repairing symptomatic articular cartilage defects of the knee (including a review of TA89) (ID686). Expected July NICE technology appraisal. The use of autologous chondrocyte implantation for the treatment of cartilage defects in the knee joints (TA89). May NICE interventional procedures guidance. Arthroscopic radiofrequency chondroplasty for discrete chondral defects of the knee (IPG493). June NICE interventional procedures guidance. Mosaicplasty for knee cartilage defects (IPG162). March Other Guidance American Physical Therapy Association. Knee pain and mobility impairments: meniscal and articular lesions. Clinical practice guidelines linked to the international classification of functioning, disability, and health from the orthopaedic section of the American Physical Therapy Association CURRENT TREATMENT OPTIONS Current treatment options include analgesics for relief of symptoms, knee lavage with or without debridement (removal of damaged cartilage), and procedures to re-establish the articular surface 3. Interventions that aim to re-establish the articular surface include 3,a : Marrow stimulation techniques (abrasion arthroplasty, drilling and microfracture) Mosaicplasty (osteochondral transplantation) Autologous chondrocyte implantation (ACI), e.g. ChondroCelect; MACI; unbranded ACI Osteotomy (rare in young patients [those aged 18-40] a ) Knee replacement (rare in young patients a ). a Expert personal opinion. 3

4 EFFICACY and SAFETY Trial NCT , cod16hs13, ; spheroids of human autologous matrix-associated chondrocytes vs microfracture; phase III. NCT , cod 16HS14, ; spheroids of human autologous matrix-associated chondrocytes; phase II. Sponsor Co.don Co.don. Status Ongoing. Ongoing. Source of Trial registry 1. Trial registry 7. information Location EU (not UK). EU (not UK). Design Randomised; active-controlled. Randomised. Participants n=150 (planned); aged years; ICRS b grade III or IV single defect chondral lesions on femoral condyles; 1-4cm 2 after debridement to healthy cartilage, 6mm in depth. n=75 (planned); aged years; ICRS grade III or IV single defect on medial or lateral femoral condyle, trochlea, tibia or retropatellar defects; 4-10cm 2 after debridement to healthy cartilage, 6mm in depth. Schedule Randomised to spheroids of human autologous chondrocytes, at spheroids/cm 2 ; or microfracture. Randomised to spheroids of human autologous chondrocytes, at 3-7, 10-30, or spheroids/cm 2. Follow-up Up to 5 years follow-up. Up to 5 years follow-up. Primary Knee injury and osteoarthritis outcome KOOS. outcome/s score (KOOS). Secondary outcome/s Expected reporting date MOCART c (MRI score); arthroscopy and biopsy; ICRS visual histological assessment score; Bern score d ; IKDC e ; Lysholm score f ; absence from work; safety. Q Q ESTIMATED COST and IMPACT MOCART (MRI score); arthroscopy and biopsy; ICRS visual histological assessment score; Bern score; IKDC; Lysholm score; absence from work; safety. COST The cost of spheroids of human autologous chondrocytes for cartilage defects is not yet known. IMPACT - SPECULATIVE Impact on Patients and Carers Reduced mortality/increased length of survival Other: Reduced symptoms or disability No impact identified b International Cartilage Repair Society clinical cartilage evaluation system. c Magnetic Resonance Observation of Cartilage Repair Tissue d Assessment of cartilage repair success. e International Knee Documentation Committee score f Tegner Lysholm Knee Scoring Scale assesses how knee pain affects quality of life. 4

5 Impact on Health and Social Care Services Increased use of existing services: procedure required to harvest chondrocytes for transplantation Re-organisation of existing services Other: Decreased use of existing services: may be potential for reduced need for other operative procedures, but this is untested at present. Need for new services Impact on Costs and Other Resource Use Increased drug treatment costs Other increase in costs. Other: uncertain unit cost compared to existing treatments Reduced drug treatment costs Other reduction in costs: Other Issues Clinical uncertainty or other research question identified: unknown long-term efficacy. REFERENCES 1 ClinicalTrials.gov. Efficacy and safety study of co.don chondrosphere to treat cartilage defects. Accessed 22 October Co.don. Half year report Teltow: Co.don; National Institute for Health and Care Excellence. Autologous chondrocyte implantation for repairing symptomatic articular cartilage defects of the knee (including a review of TA89). Final scope. London: NICE; May National Institute for Health and Clinical Excellence. The use of autologous chondrocyte implantation for the treatment of cartilage defects in the knee joints. Technology appraisal TA89. London: NICE; May National Institute for Health and Care Excellence. Knee cartilage defects autologous chondrocyte implantation: final protocol. London: NICE; July Logerstedt DS, Snyder-Mackler L, Ritter RC et al. Knee pain and mobility impairments: meniscal and articular cartilage lesions. Clinical practice guidelines linked to the international classification of functioning, disability, and health from the orthopaedic section of the American Physical Therapy Association. Journal of Orthopaedic and Sports Physical Therapy 2010;40(6):A1-A35. 7 ClinicalTrials.gov. Assessment of efficacy and safety of 3 different doses of co.don chondrosphere to treat large cartilage defects. CS&rank=2 Accessed 24 October