ANNUAL FINANCIAL REPORT 2010 2010 - TiGenix

In June 2010, TiGenix presented the results of the follow-upuntil 5 years post-surgery. The results confirm the durabilityof the therapeutic effect of ChondroCelect and demonstratethe importance of early intervention. Early treatment withChondroCelect resulted in a superior clinical benefit overmicrofracture and a lower failure rate. Conversely, patientswho had experienced symptoms for five years or more priorto treatment did not derive substantial long-term benefit fromeither treatment.The pivotal TIGACT01 trial data have been complemented bysupplementary information from an open label trial and otherclinical programmes:• an open label trial for the treatment of complex cases at theBelgian military hospital;• an expanded access programme for the treatment ofcomplex and salvage cases at three hospitals in Belgium;• a compassionate use (named patient) programme inBelgium, the Netherlands, Germany and the UK.In total, circa 550 patients have been treated withChondroCelect to date.No unexpected safety issues were observed and bothtreatment groups had a comparable safety profile.ChondroCelect resulted in more cartilage hypertrophy (usingperiost), joint crepitation & joint swelling (post operative) ascompared to the reference treatment microfracture.Regulatory situationTiGenix is the first company that succeeded in obtainingcentral regulatory approval for a cell-based medicinal productin Europe, and ChondroCelect is the first and currentlyonly approved product under the new ATMP regulatoryframework for innovative cell-based, tissue-engineered, andgene therapy medicines. As part of the conditions associatedwith the marketing authorisation of this first ATMP, TiGenixwill ensure follow-up of the efficacy and safety of theChondroCelect product in post-approval studies, as describedin an approved risk management plan. In this context, aconfirmatory prospective, multi-center, randomized controlledtrial of ChondroCelect versus microfracture for the repair ofsingle cartilage lesions in the femoral condyle of the kneehas been requested by the EMA. The objective of this postapprovalcommitment is to compare the efficacy and safety ofChondroCelect versus microfracture in lesions 1-≤4 cm² and toassess efficacy and safety of ChondroCelect in lesions >4 cm².ChondroCelect will be compared to microfracture in a patientpopulation with early onset (≤3 years), and single, symptomatic,ICRS grade III-IV cartilage lesions of 1-≤4 cm² diameter in thefemoral condyle of the knee. The use of ChondroCelect willalso be assessed in patients with early onset (≤3 years), single,symptomatic, ICRS grade III-IV cartilage lesions of >4 cm²diameter in the femoral condyle of the knee. In agreement withthe EMA, this post-approval study is expected to start in thefirst half of 2013.In the US, the Company filed an IND application forChondroCelect in 2005, allowing it to discuss theChondroCelect development with the FDA (CBER) in view ofsubmitting a BLA. On March 15, 2010, TiGenix was informedby the FDA that a new confirmatory study would be requiredbefore the filing of a BLA. In view of the additional investmentassociated with a new clinical trial in the US, TiGenix decidedto pursue corporate partnering opportunities for the furtherdevelopment and commercialization of ChondroCelect inthe US. Meanwhile the US development activities have beenput on hold, with the exception of the preparations to seekSpecial Protocol Assessment (SPA). A US study protocol, basedon the design of the planned European confirmatory trial andincluding additional recommendations of the FDA is beingfinalized. The timing of submission will be dependent on theoutcomes of the co-development partnering discussions.Commercial launch in EuropeChondroCelect is the first cell-therapy product in Europe thatis commercialized as a medicinal product. Based on the clinicalevidence that has been developed over the years of productdevelopment, the product is being positioned as a first-in-classmedicinal product for knee cartilage regeneration.Although central approval has been obtained, a staged launchstrategy is being followed for making the product eligible formarket launch in the entire European Union. For the first phaseof launch TiGenix is targeting about 50-60 leading orthopaediccentres. The centres have been identified and selected, andmost of the physicians in these centres have already beentrained. Several of the physicians in these centres have alreadyhad the opportunity to use ChondroCelect in the context ofthe clinical trials and/or compassionate use (named patient)programme.117 •