Making a commercially successful gene therapy

Developing a commercially successful gene therapy is challenging and requires balancing several different considerations. Having a clinically effective therapy is necessary but not sufficient to ensure product success. Additionally, reimbursement, quality, regulatory considerations, and manufacturing also must be taken into account.

Reimbursement

With the development and approval of several therapies in the last few years, reimbursement is now the primary bottleneck in the successful commercialization of gene therapies. Gene therapy is a one-time, potentially curative treatment that generally comes at a very high cost. This therapy contrasts with most current therapies which require ongoing treatment.

This change in treatment regime can prove taxing to payers (such as insurance companies and national health care providers) and is an area where considerable innovation is needed as payment models diverge from value-based pricing toward more outcome-based models.

For example, in the US, the list prices for Yescarta and Kymriah are $373,000 and $475,000 per patient, respectively (1,2). The cost for Luxturna is $425,000 per eye, making them among the most expensive drugs available on the market today (3). Novartis has suggested a risk-sharing approach where they will absorb the cost of Kymriah if it does not work on the patient (2).

Regulatory agency and approval process

In recent years, regulatory agencies have been particularly active in enabling gene therapies to navigate the regulatory pathway with the development of the advanced therapy medicinal product (ATMP) and regenerative medicine advanced therapy (RMAT) designations in Europe and the US, respectively. These designations along with both Breakthrough Therapy and Orphan Drug designation, which are also frequently applied to cell and gene therapies, allow for an expedited regulatory pathway for drugs that demonstrate the ability of cure or modify serious, life-threatening diseases that are currently without existing effective treatments. These designations can lead to a shorter time to approval, and it is estimated that breakthrough therapy products are approved within an average 5.2 years from IND application, compared to 7.4 years for a non-breakthrough therapy. RMAT designations have so far been granted to > 30 drugs, which indicate the popularity of using this route (4).

Implications for manufacturing

Manufacturing sufficient product with the necessary quality is an area that requires significant effort and knowledge. The challenges around reimbursement and the potential for shorter approval times both put pressure on the development of an optimal manufacturing processes where the cost of manufacturing needs to support any proposed selling price; and process development time is short. There are several examples of where the balance between these various factors has not been struck successfully. Glybera was approved by the European Medicines Agency in October 2012, making it the first virus-based gene therapy on the market. Unfortunately, despite a price of EUR 1 million, the cost of manufacturing was too high to make a profit, and, with a very low patient demand, the product was withdrawn from the market in 2017 after only one patient was treated (5).

The future

While there are many challenges to overcome to successfully commercialize a gene therapy drug, the results across different gene therapies are phenomenal, revolutionary, and life changing. The widely documented benefits and patient success stories continue to grow.

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