After US approval, Vericel’s headache begins
FDA approval of MACI, Verticel’s autologous chondrocytes for knee cartilage replacement, marks the first ever green light for this kind of third-generation product in the US, but the group could find that overcoming any regulatory reluctance was the least of its problems.
Autologous chondrocytes products have a lamentable track record, and both MACI and its one-time fierce rival, Tigenix’s Chondrocelect, were launched in the EU but then voluntarily withdrawn. Chondrocelect’s status as the EU’s first ever cell-based product approval is now a meaningless footnote, and Vericel will hope that a parallel fate does not befall MACI in the US.
A big difference between the EU and the US, of course, is the greater capacity of patients in the latter jurisdiction to pay privately. And Vericel has spent a considerable amount of time and money getting MACI to this stage: a two-year pivotal programme named Summit was followed by a three-year extension study, and the BLA was finally accepted in March.
This investment was necessary for MACI to have any chance of making a dent in the market. Vericel’s previous autologous chondrocyte product, Carticel, has been available in the US since 1997, but until the postmarketing Star trial was published 10 years later it had no backing from controlled clinical studies.
Vericel will hope that Summit data provide the necessary impetus to spur MACI prescribing; it initially wants to target Carticel users and doctors who might have given up on Carticel owing to its complexity. In Summit knee function and pain scores backed MACI over microfracture bone marrow stimulation, and similar patient-reported outcomes supported Carticel in Star.
In Europe it was lack of reimbursement that ultimately did for MACI and Chondrocelect alike, and Tigenix also blamed an unclear regulatory environment.
While it had assumed that central approval – no mean feat – would give Chondrocelect a unique selling point, it was dismayed subsequently to find that hospitals in Spain and Germany were allowed to continue producing advanced therapy medicinal products without EMA marketing authorization.
This effectively wiped out Chondrocelect’s market, and the product was formally pulled last month, seven years after launch. Market authorisation for MACI, meanwhile, was suspended in 2014 when Vericel closed its EU manufacturing site.
MACI stands for matrix-induced autologous chondrocyte implantation, and the procedure involves expanding a patient’s healthy chondrocytes and seeding them onto a porcine-derived bio-resorbable membrane, which is then placed over the damaged area of the knee. MACI is the first FDA-approved product that applies tissue engineering to grow autologous cells on scaffolds, Verticel says.
Carticel and MACI were originated by Genzyme, but in 2013, after Sanofi acquired Genzyme for its rare disease franchise, the French big pharma firm sold this cell therapy and regenerative medicine business to Aastrom Bio. Aastrom was later renamed Vericel.
Whether MACI’s US success could spur Chondrocelect to be revived seems doubtful; that would require a US clinical programme to be started from scratch. Tigenix sold Chondrocelect EU rights to Swedish Orphan Biovitrum and its cell therapy production plant to Pharmacell, a contract manufacturer.
In the meantime, Tigenix turned to Cx601, an allogeneic stem cell project for treating anal fissures. Vericel, too, has backed several horses, and its heart failure stem cell therapy ixmyelocel-T disappointed in phase II this year.
Vericel opened up 57% this morning, so clearly the US approval has given MACI a second lease of life. But the precedent of Carticel, which sold just $35m last year, shows that the jury is still out as to whether an autologous chondrocyte product can be commercially viable.