The first approved gene therapy in the EU is scheduled to go on sale shortly at a price of €1.1M per treatment. The product, marketed as “Glybera alipogene tiparvovec”, is an adeno-associated virus vector (AAV) carrying the lipoprotein lipase (LPL) gene designed to treat LPL deficiency in patients with recurring, acute pancreatitis. According to a pricing dossier filed with Germany’s Federal Joint Committee by Italian company, Chiesi Farmaceutici S.p.A (Parma, Italy), the retail price of the therapy will be €53,000 per vial, for which a 62.5kg patient would require 21 vials for treatment, totalling €1,113,000 per patient. As of June 2014, there were 33 gene therapy clinical trials underway for ophthalmic disorders and a renewed commercial interest from large pharma has created an investor friendly environment for novel technologies with high unmet medical need.
The company behind Glybera is a Dutch pharma, “uniQure”, currently quoted on the US NASDAQ with a market cap of approximately $250M. Navigating approval through the EMA required 4 attempts and almost 2.5 years during which uniQure’s predecessor (Amsterdam Molecular Therapeutics Holdings NV, “AMT”) lost practically all its institutional investors, a significant number of employees and ended up having to go private to fund development of the product. The indication for Glybera, LPL deficiency, is a rare recessive disorder and, according to uniQure’s CEO Joern Aldag, affects about 10,000 people worldwide. In June 2011, EMA’s Committee for Medicinal Products for Human Use (CHMP) gave its first negative opinion. On a second occasion, following a further submission from the company, CHMP again rejected the product citing a number of issues regarding efficacy and insufficient long-term data. By this time, uniQure’s predecessor (AMT) had all but collapsed in share price and needed to go private requiring approximately €6M in funding to keep the program going. On a third attempt to gain approval at the EMA, in April 2012, the application was again rejected by CHMP with a vote of 16-15 in favour however, the rules required a vote of 17 members of the committee to be in favour for approval to be provided (one member of the committee was understood to have been ill at the time of the vote). Following a third rejection the CHMP then invited uniQure to request a re-examination however, the vote on the re-examination in July 2012 was not disclosed, instead a statement by CHMP’s acting Chair, Tomas Salmonson reported: “Additional analyses by CAT have added to the robustness of the data provided and allowed CHMP to conclude that the benefits of Glybera are greater than its known risks.” While the experience may have been bruising for the company, the path to regulatory approval, should in theory provide additional confidence to other sponsors that gene therapy products are approvable and viable in the EU spurring further innovation of novel technologies for currently incurable diseases.
While there are many large and small companies developing a broad range of gene therapies for ocular disorders, the price of such ocular medicines is not expected to reach such price tags as that sought by Chiesi for Glybera. Many of the ocular disorders that are now undergoing clinical development are not as rare as LPL deficiency and therefore the economic model for sponsors to recover costs and generate profit may be quite different that that of Glybera. Nevertheless, orphan markets have now clearly demonstrated that an attractive return on investment is possible which will serve to bring further capital into this space generating further innovation. Given the immune privileged status of the enclosed eye, coupled with other suitable aspects for gene therapy, the field of ophthalmology is poised to be a major beneficiary of these new therapeutic approaches.