This article first appeared in Cell and Gene
Cell and gene therapies are finally becoming a reality, with hundreds of clinical trials underway and some major therapeutic breakthroughs already reaching the market. In the past year alone, the FDA approved its first gene therapy, Spark’s Luxturna for the treatment of a rare form of vision loss, as well as the first two CAR T-cell therapies, Novartis’s Kymriah and Gilead’s Yescarta, for certain forms of blood cancer. While this certainly marks the beginning of an exciting period in the development of cell and gene therapies — the culmination of decades of development — the future impact of cell and gene therapies is uncertain.
Will their use become ubiquitous, changing the landscape forever as many have promised they would? Or will applications be confined to rare diseases as they have been thus far? The answer largely hinges on the advancement of science and whether or not we are able to uncover the genetic causes for some of today’s greatest medical challenges. However, challenges also remain around how willingly payers, providers, and patients will adopt these therapies, either due to their safety, efficacy, and/or long-term costs.
Working through these uncertainties, we explore four very different scenarios that could unfold over the next decade. Based on extremes, these scenarios will expand traditional thinking and help life science companies determine the appropriate position and strategy:
This is the most optimistic of our scenarios, requiring a number of factors to come to fruition. Imagine if not only are cell and gene therapies proven to be safe, but technological breakthroughs also allow for the use of allogeneic sources — i.e., using cells from any donor that is an acceptable HLA (human leukocyte antigen) match for the patient, as opposed to having to use cells from the patient themselves. In the case of CAR T-cells, this discovery would overcome one of its biggest manufacturing hurdles, allowing prices to drop significantly from their current half million-dollar price tags. Competition in the field would rise sharply, resulting in the proliferation of cell and gene therapies for an even greater number of applications. As a result, the advantage would be with early movers, especially those that are able to build and cultivate fruitful partnerships and collaborations, and those who are able to crack the supply chain challenge by introducing higher degrees of automation, bringing costs down even further. Cell and gene therapy would only be limited by how quickly science could identify and validate targets for treatment.
If highly personalized therapies (e.g., autologous cell therapies that require the use of cells from the patient themselves) are the only ones that prove to be scientifically viable and safe, cell and gene therapies may inevitably remain expensive and difficult to reimburse. These personalized therapies need to be developed and customized for each individual patient. As a result, per-unit production cost will remain high even as production levels rise. Moreover, these therapies involve multiple sites of care and multiple high-cost procedurs, further complicating the issue. As a result, cell and gene therapy will end up as a luxury, boutique field of medicine. Small, privately funded companies may then rise to meet the demand of those who have the funds to pay for these expensive therapies. Therapies such as cosmetic stem cell treatments would end up being administered in private luxury clinics that have in-house cell and gene therapy manufacturing capabilities and a major focus on patient care.
Can old dogs learn ingenious new tricks?
If clinical trials for cell and gene therapies become marred with safety issues, adoption will be slow and could be overshadowed by lower-cost, safer options. In 2017, Juno Therapeutics, together with Kite Pharma and Novartis, were considered the frontrunners of CAR T-cell therapies. However, that all changed when five patients died during a pivotal study of Juno’s leading CAR T-cell candidate, dooming the trial and delaying Juno by at least two years. Imagine if such issues persist in cell and gene therapy trials — regulations for these products, which are already developing slowly, would become even stricter. Even if approved, given their much higher price tags and previous history of safety issues, payers will be even more hesitant to reimburse them, adapting a wait-and-see stance to determine if cell and gene therapies actually provide enough of a health econometric benefit. Moreover, without clear evidence of benefits and given the high-profile nature of these therapies in the media, they could also struggle to win over doctors and their patients. In this scenario, companies will only succeed if they have good safety data and effective clinical engagement and are able to establish robust outcomes-based contracts.
Finally, imagine a scenario where the development of cell and gene therapies for complex diseases is never successful. This could stem from an inability to develop therapies that target diseases with multiple genetic components or from the genetic basis remaining undeciphered. Regardless, cell and gene therapy would be restricted to rare diseases. From the drug manufacturer’s point of view, as therapies — potentially curative therapies — are devised for rare disease with the greatest patient populations, the field will grow increasingly unattractive for further development. The FDA will need to provide additional incentives (e.g., by allowing longer periods of exclusivity for orphan drugs). At the same time, drug manufacturers will work with regulators to further decrease barriers to approval. Given the lack of patients for many rare diseases, trials for will need to utilize digital solutions, especially for recruitment, and become shorter, with combined phases that show both safety and efficacy. Later-stage trials will be replaced with rollover studies to demonstrate the longer-term effects of treatment.
While it remains to be seen which, if any, of these scenarios comes to fruition, we are confident that cell and gene therapies are the future. It is likely that the path to success for cell and gene therapy will consist of a combination of our imagined scenarios. It is also possible that none of these scenarios will come true at all. Regardless, it is important that life science companies consider the future and begin planning now to foresee challenges and redefine the world of tomorrow. Is your organization ready?