It is one thing to research and develop an advanced therapy medicinal product (ATMP), but quite another to bring it successfully to market. Among the nine ATMPs approved in Europe since 2009, only five are still on the market.
The reasons for the slow commercial acceptance of these products were discussed at the Phacilitate cell and gene therapy conference in Berlin, Germany on 21 September 2017.
Four reasons were given. First, the ATMPs were developed in a research setting before a regulatory pathway existed for commercialisation. As a consequence, there were few if any accepted business models for bringing these products to market at the time of approval. “Many of these products were not developed for the commercial world initially,” Diego Ardigò of Chiesi Farmaceutici SpA, told the meeting.
Second, most of the products treat rare conditions for which very few patients exist. In some cases, the number of eligible patients is far fewer than the developers had expected. Third, the novelty of the products makes it difficult to demonstrate value to payers. This is especially true in cases where the product claims to be a one-time treatment for a serious disease. Measuring patient response is critical, but the criteria for doing so are still being developed, Dr Ardigò said. Finally, some of the ATMPs have faced stiff competition from unlicensed hospital-based products which are allowed in Europe under an exemption to the legislation governing ATMPs.
To date, four of the first nine ATMP products have been or about to be, withdrawn from the market. The reasons are entirely commercial.
The first, ChondroCelect, is an autologous tissue-engineered product for the repair of cartilage defects in the knee. It was approved in October 2009 but encountered competition from unlicensed hospital-based products. The developer, TiGenix NV, withdrew the product in July 2016.
The second, Maci, is an autologous tissue-engineered product also developed for the repair of cartilage defects of the knee. It received a European marketing authorisation in June 2013 but the licence was suspended in late 2014 with the closure of the product’s manufacturing plant in Denmark. This followed the sale by the developer, Sanofi SA, of its regenerative medicines business to Aastrom Biosciences Inc (now Vericel Corp) and the US company’s decision to stop selling Maci in Europe.
The third product, Provenge, is an autologous cell therapy product for the treatment of prostate cancer. It was approved by the European Commission in September 2013 and withdrawn from the market in May 2015 after its developer, Dendreon Corp, filed for bankruptcy. A key reason for its commercial failure was the high cost of producing, transporting and administering the therapy.
Finally, the western world’s first approved gene therapy, Glybera, received a European approval in November 2012, but the developer uniQure NV has decided to let the marketing authorisation expire on 25 October of this year.
Glybera was a focus of the discussion because of its novelty and its price. It was launched at €1.3 million – a record high. The product was assessed by health technology officials in Germany and qualified for reimbursement, but at the end of the day, only one patient was treated. Glybera was developed to treat lipoprotein lipase deficiency, a rare disease where the body can’t break down fats leading to pancreatitis. Because the incidence is low, the proof of efficacy in the trial leading up to approval was based on a small sample.
Detlev Parow of the German insurer DAK-Gesundheit, told the meeting that the one patient “had patient-relevant improvements but was not cured.” To date, the patient still has elevated fat levels in the blood, requiring a restricted diet. On the other hand, the patient has been able to return to work.
The meeting also reviewed the status of three ATMP products currently on the market. These are Holoclar, for the repair of cells on the epithelium of the cornea resulting from burns; Strimvelis, a gene therapy for the treatment of ADA-SCID immunodeficiency; and Zalmoxis, an adjunctive treatment for patients undergoing a haploidentical haematopoietic stem cell transplantation.
Strimvelis was developed by GlaxoSmithKline Plc in collaboration with the Italian biotech company MolMed SpA and is commercially available only in Italy. This means that patients from elsewhere have to travel to receive the autologous treatment. GSK reached an agreement with the Italian reimbursement authority to price the product at €594,000 for a one-time treatment with a money-back guarantee if the product does not work. The first patient was treated earlier this year.
A similar pricing model has been adopted by Novartis whose gene therapy for a childhood leukaemia, Kymriah, was approved by the US Food and Drug Administration in late August. The product has yet to be approved in Europe. Under this approach, payments will only be made if patients respond to the treatment by the end of the first month.
- Victoria English, 24 September 2017.
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