Date: 2016-12-13
Type of information: Granting of a Market Authorisation in the US
Product name: MACI™ (Matrix applied characterised autologous cultured chondrocytes)
Compound: Matrix applied characterised autologous cultured chondrocytes
Therapeutic area: Bone diseases - Regenerative medicine
Action mechanism: cell therapy. MACI™ is a cell therapy product. This advanced therapy medicinal product (ATMP) is to be available as an implantation matrix consisting of characterised autologous cultured chondrocytes on a collagen membrane (500,000 to 1,000,000 cells per cm2), to be trimmed and implanted into the cartilage defect of the damaged knee. The amount of Maci administered depends on the size of the cartilage defect, and is trimmed to ensure that the damaged area is completely covered. Multiple implants may be used if there is more than one defect. This third-generation autologous chondrocyte implantation (ACI) product for the treatment of cartilage defects in the knee was the first tissue-engineered product approved under the Advanced Therapy Medicinal Product guidelines by the European Commission. On April 21, 2014, Vericel has entered into a definitive agreement to acquire Sanofi's Cell Therapy and Regenerative Medicine (CTRM) business for a purchase price of $6.5 million, with $4 million payable in cash at closing and $2.5 million payable in the form of a promissory note.
Company: Vericel (USA - MA)
Disease: repair of symptomatic, full-thickness cartilage defects of the knee in adult patients
Latest news: * On December 13, 2016, the FDA approved Maci™ (autologous cultured chondrocytes on porcine collagen membrane) for the repair of symptomatic, full-thickness cartilage defects of the knee in adult patients. Maci™ is the first FDA-approved product that applies the process of tissue engineering to grow cells on scaffolds using healthy cartilage tissue from the patient’s own knee. Administration should be performed by a surgeon specifically trained in the use of Maci™. The safety and efficacy of Maci were shown in the two-year SUMMIT study (Superiority of MACI implant versus Microfracture Treatment in patients with symptomatic articular cartilage defects in the knee), designed to demonstrate reduced pain and improved function in comparison to microfracture, an alternative surgical procedure for cartilage repair. The trial included 144 patients (72 in each treatment group). A majority of the patients who completed the two-year clinical trial also participated in a three year follow-up study. Overall efficacy data support a long-term clinical benefit from the use of the Maci implant in patients with cartilage defects. The most common side effect reported by people who received Maci were: joint pain, common cold-like symptoms, headache and back pain. * On January 4, 2016, Vericel announced that it has submitted a Biologics License Application (BLA) to the FDA for MACI™ (matrix applied characterized autologous cultured chondrocytes), the company's investigational autologous cellular product intended for the treatment of symptomatic cartilage defects of the knee in adult patients. MACI™ was studied in the pivotal Phase 3 clinical trial SUMMIT ("Superiority of MACI Implant to Microfracture Treatment") and the three-year SUMMIT Extension trial. SUMMIT was a two year, prospective, multicenter, randomized, open-label, parallel-group clinical trial designed to evaluate the safety and efficacy of MACI to reduce pain and improve function compared with arthroscopic microfracture in the treatment of patients (n = 144) with symptomatic Outerbridge Grade III or IV focal cartilage defects. The SUMMIT Extension trial evaluated the safety of both treatments for an additional three years. * On June 10, 2015, Vericel announced that following discussions with the FDA the company plans to submit a Biologics License Application (BLA) to the FDA by the end of 2015 for MACI™ for the treatment of focal chondral cartilage defects in the knee. * On 25 April 2013, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a marketing authorisation for MACI, an implant intended for the repair of symptomatic, full-thickness cartilage defects of the knee in adult patients.MACI is an advanced therapy medicinal product (ATMP). It is to be available as an implantation matrix consisting of characterised autologous cultured chondrocytes on a collagen membrane (500,000 to 1,000,000 cells per cm2), to be trimmed and implanted into the cartilage defect of the damaged knee. The product’s ATC code is M09AX02.MACI has been investigated in a randomised, open-label parallel-group trial in which MACI was compared with microfracture surgery in 144 adult patients with knee cartilage defects (grade III and IV of the Modified Outerbridge Scale) ranging between 3 and 20 cm2 in surface area. At week 104, MACI was superior to microfracture in improving pain and knee function, with significantly more MACI treated patients responding to treatment than microfracture patients (63 of 72 [87.50%] vs. 49 of 72 [68.06%], P= 0.016). Response to treatment was defined as an improvement of the Knee Injury and Osteoarthritis Outcome Score (KOOS) of at least 10 points for both pain and knee function. With regard to safety, MACI has been causally linked to symptomatic graft hypertrophy and graft delamination. Patients may also have peri-operative complications related to surgical intervention. A pharmacovigilance plan for MACI will be implemented as part of the marketing authorisation.
Patents:
Submission of marketing authorization application USA : 2016-01-04
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2016-12-13
UE authorization: 2013-06-27
Favourable opinion UE: 2013-04-25
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news: * On 5 September 2014, the new marketing authorisation holder for MACI, Aastrom Biosciences closed the EU manufacturing site for the medicine, which is located in Denmark. Consequently, the licence of the manufacturing site was withdrawn. MACI is unavailable for new patients in the EU until a new manufacturing site has been registered in the EU. The closure was due to commercial reasons and the safety and effectiveness of MACI has not changed. The European Medicines Agency has been working with the marketing authorisation holder since June 2014 to ensure that patients who had already started the treatment procedure were able to complete their treatment. A letter was sent to healthcare professionals informing them of the site closure and requesting that they notify the marketing authorisation holder of those patients who wish to complete their treatment. In addition, surgeons were asked not to start new patients on MACI.
Following the closure of the site, the marketing authorisation holder has been requested to store any remaining biopsies that have not yet been used to allow for potential later treatment with MACI, unless patients and their treating surgeons have explicitly indicated that they do not wish to complete treatment with MACI. Last June, Aastrom Biosciences acquired MACI with Sanofi's Cell Therapy and Regenerative Medicine (CTRM) business and announced that the Denmark manufacturing facility, licensed for commercial production in the EU, will be sold.
