Signals Blog


With contributions from blogger David Brindley

September 2015 has been an historic month for regenerative medicine. For the first time ever in the Western world, a prescription has been issued for a gene therapy, Glybera. At the ESGCT and FSGT Collaborative Congress, Helsinki, this news was welcomed and spurred discussion on broader challenges in the gene therapy field.

In 2012, alipogene tiparvovec, trade name Glybera (UniQure, Netherlands) became the first gene therapy to receive marketing authorization in the West, for the treatment of liprotein lipase deficiency in adults – a rare genetic disorder in which a person lacks a protein needed to break down fat molecules – with severe pancreatitis. However, various setbacks have resulted in a highly unusual delay between approval and first use as a marketed product. Across the whole of Europe, just 150 to 200 patients are eligible for treatment with Glybera; this, and numerous difficulties in commercializing the medicine, have resulted in an astounding and record breaking price tag of ~€1.1 million to treat a single patient.

As we have previously discussed, pricing of potentially curative medicines is challenging. Gene therapies epitomize these challenges: not only do they have high cost of goods, but they are often used for diseases with small patient populations, which, somewhat ironically, become smaller still as patients are cured successfully. As noted by Alec Orphanidis, UniQure, prices for gene therapies must be triangulated according to these factors, and others such as benefits to society or reduced burden in the clinic in the long-term. As noted in a recent Nature Biotechnology editorial, the payer’s perspective must be considered.

Aside from appropriate pricing, several valuable “key points to success in gene therapy” were raised by Nigel Parker, Chairman and CEO of FKD Therapeutics Oy, and former CEO of Ark Therapeutics, who led the first MAA for a gene therapy, Cerepro, in 2004.

First, the gene therapy industry is undoubtedly populated by expert scientists doing exceptional science. The issue is that those who have the role of funding gene therapy companies and research may not be expert scientists. Too little attention is given to the need for effective communication of science into language that enables investors to evaluate it as a business opportunity, not just as exceptional science. (We commend CCRM for encouraging its bloggers to do just this.) Indeed, too little attention is given in the first place to the issue of whether the science actually has a clear, commercial application. If not, however great the science behind the therapy, it is doomed to fail.

Second, the importance of aligning the company’s program with the appropriate funding model is pertinent. Raising venture capital is a well-trodden and often successful route in biotech, but there are downsides and alternatives. Timelines for return on investment for VC cash may be longer than desirable, particularly in the nascent and uncertain field of gene therapy. From the outset, companies seeking VC investment should recognize that a profitable exit is on the investor’s mind. Establishing partnerships may lead to more closely aligned interests, which could lead to a better chance of success. Ultimately, such decisions must be made on a case-by-case basis, but their importance should not be overlooked.

Great science is not enough to build a great company. It is clear that great people, who can bridge the gap between science and finance, and communicate and think in both languages, are of pivotal significance. The CEO, in particular, will be responsible for decisions that will ultimately ‘make or break’ the business.

When discussing gene therapies, the question “Is it worth it?” is often muttered. At such a high cost, can these products really be justified? Is it worth investing in what has proven historically to be a risky area? If there is a clear patient need addressed with appropriate business models, effective management, and exceptional science demonstrating clear, material results, this question will go away.

The regenerative medicine community should be celebrating the first prescription of Glybera for the iconic achievement that it represents. However, while significant, it must be recognized that Glybera is just the ‘tip of the iceberg.’ As an orphan medicine and a gene therapy paving a largely unmapped regulatory route, pricing for Glybera, and the numerous challenges encountered in its commercialization, do not necessarily reflect the situation for future gene therapies, such as cell-based immunotherapies, expected to reach the market soon.

Developers should learn from the challenges encountered in the pioneering approval of Glybera, and take heed of the advice outlined herein, to ensure that a healthy gene therapy industry can thrive and ultimately deliver more transformative medicines to patients who so desperately need them.

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James Smith

James Smith

James Smith is a Research Associate of the CASMI Translational Stem Cell Consortium, where his current research focuses on extracellular vesicle biomanufacturing, iPSC translation and several systematic reviews including immunotherapy, fracture healing, and the use of placebos in surgery. He recently completed a SENS Research Foundation Scholarship at the Harvard Stem Cell Institute and Jeff Karp’s Lab at the Brigham and Women’s Hospital, where he developed a computational model of extracellular vesicle bioprocessing costs. Aside from translational research, James has an active interest in basic biology, achieving a First Class undergraduate degree in Biological Sciences from the University of Oxford. You can find James on LinkedIn.