Cell and gene therapies are representing the future of medical treatments for (in some cases) diseases and disorders which had no previous viable therapeutic avenue. To some degree, a look across the landscape of cell and gene therapies today resembles a look back at the early biotech landscape, circa 1990s.

With new therapies comes the need for new technologies and approaches, and so externalizing some of the risks and drawing upon outside expertise can be tremendously helpful.

Cell therapy and gene therapy
Don’t be confused. These two names for different types of therapy are often used interchangeably, and mentioned together in the same sentence as though they’re requisite partners. They are two (very) different modalities.

Cell therapy
A treatment approach where live cells are administered in order to provoke a particular physiological effect. It’s interesting, because there’s also a lot of people in the field who refer to the work of Swiss doctor Paul Niehans as the progenitor of cell therapy. He might have been one of the first to doggedly pursue injection of living cells into people, but there was really no evidence of efficacy for any of the experiments that he did. One of which was to inject live parathyroid cells into a tetany patient whose parathyroid gland had been removed. It’s unlikely that this really resolved the condition in the long run, but history is favorable to Niehans.

Gene therapy
A treatment approach where nucleic acid is delivered to patients’ cells as a precise, targeted approach to modifying genetic expression; it’s used as a drug to elicit physiological effects for the abatement of health conditions. There’s a bit of a messy pedigree within gene therapy, because even organ and bone marrow transplants have been found to introduce foreign DNA to patients and therefore could be a form of gene therapy. But the vision of gene therapy is to have the field focus on the ‘precise and targeted’ genetic changes, and not just the introduction or inclusion of uncontrolled genetic material and information into patients.

Risks
Any time we introduce cells, genetic material, or attempt to modify genes, we run into several very serious and salient risks. Immunogenicity, off-target sequelae, physiological compensatory mechanisms, and other unintended consequences are part of these treatments. Unfortunately, the public is ill-equipped to assess or understand risk, let alone risks like these from novel and nascent medical therapies. As you read this, the FDA, Wall Street, and small segments of the general public are watching with great interest the fate of the drug Zolgensma. It’s a one-time treatment for spinal muscular atrophy (SMA), and a patient has recently died potentially as a result of the therapy. It’s an unfortunate position for AveXis Inc. and Novartis, who have developed this treatment. Unfortunate because we never want events like these to be linked in a clinical trial to a prospective drug treatment, but also because the overall risk:benefit calculus shouldn’t be so myopic as to potentially halt a therapy as a result of a single death. There’s more to the situation than this, but any treatment carries risks with it—up to and including death. We also need to advocate for good science in the face of public misperception and potential fear mongering.

A lot on the horizon, but what changes in the landscape?
I’ll say here that cost models abound—I’ve even seen valuations up to, and including, a market volume of $1 trillion for CAR-T (a type of cell therapy) by the year 2030. For the entire cell and gene therapies markets, even greater. Of course, all models are wrong, but they can give us some directionality to our thinking and forecasting for the future.*

In some current cohorts, there’s about a 3-5 year time horizon until the cell or gene therapies make it to market. Many at the moment are for different types of cancers, with a lot of attention on hematological malignancies such as acute myelogenous leukemia, chronic lymphocytic leukemia, and myelodysplastic syndrome. Solid cancers have been garnering more attention for treatments over the past few years, yet treating these types of malignancies comes with its own challenges.

The case for outsourcing
The need for trained staff, reasonable labor costs, precision manufacturing facility infrastructure, and a favorable regulatory landscape are four major factors shaping what the future of cell and gene therapies will look like. These aren’t just implicit factors that exist regardless of how we progress to the future of these treatments. These factors are instead tremendously high-leverage variables that will themselves partly shape and create the future of these treatments. One thing we know based on the trajectory of medicine over the last several decades: cell therapy and gene therapy treatments will not be inexpensive, they differ from current standards-of-care, and this also means that their growing presence will usher in a new era of discussions with payers, patients, prescribers, and within the financial markets. Where we land with their usability (utility), financial viability, and the place that they will occupy in our future zeitgeist are all yet to be determined.

Chart 1 shows the relative competitive landscape for gene therapy treatments, where the red end of the spectrum is where competition is high for a particular disease, and the blue end represents where competition is relatively low.¹


Enter Sandeman
If you enjoy wine (which really, you should, because it has salubrious properties), there’s an analogy between outsourcing of cell and gene therapies and changes in product lines at wineries. Within the world of wines, there is the subset called port. Port is a type of fortified wine which has different fermenting and aging, and so has a very different set of characteristics. One of the leading port manufacturers, Sandeman, was looking to meet the next generation of consumers’ needs with a selection of new products. Their line, according to business development staff and the design specialist outfit they hired, took 18 months from conception to roll-out.

Says their marketing manager, “Sandeman is at the fore-front of the category and we wanted to communicate its higher pedigree. We want to encourage people to think about port in a different way. Aged tawnies are our strong suit and are highly versatile but under-appreciated in the UK.”


In order to make these forward-looking changes, they had to revamp and overhaul technical infrastructure to produce new product for the future, which also changed their supply chain dramatically. Financially, there’s a great deal of risk within the food and beverage industry just as within pharmaceuticals. In fact, the segment that Sandeman was attacking represented a 5% share of the overall port category but it was growing at around 30%, according to figures released by the Port and Douro Wine Institute (IVDP), compared with the overall volume growth of the category of 1%. So the take-home message here is that business is business, and though the cell and gene therapy segments within healthcare have a tremendous amount of uncertainty within them, it’s not a reason to shy away from pioneering the future. Outsourcing organizations can tend to be more nimble and effective with logistical and infrastructure changes than sponsors.

Taking into account the factors I’ve listed above, cell and gene therapy outsourcing offers compelling benefits, and brings with it some risks—but at the same time allows organizations to modify their own internal risk profile, which can lead to a significant reduction in overall risks in some cases. Clinical trial viability of candidate drugs, regionally-specific regulatory favorability, and changes to regulatory framework to evaluate cell therapies and gene therapies can all lead your internal business calculus to determine that partnering with an outsourcing vendor offers your organization a tremendous set of benefits. If you elect to go that path, there are several qualified vendors to help you in your quest to bring your candidate drug to market. 

*Note: I’m using some of the eminent statistician George E.P. Box’s wisdom here, as he observed, “All models are wrong, but some models are useful.”

References

1. Signals Analytics. (2019). Signals playbook. https://signals-analytics.com/platform/#
2. Paula Anne Ford-Martin; Tish Davidson (2011), “Cell therapy”, in Laurie J. Fundukian (ed.), The Gale Encyclopedia of Medicine, 2 (4th ed.), Gale, pp. 885–887

---

Ben Locwin

Ben Locwin, PhD, MBA, MS, MBB began his foray into healthcare decades ago after he started out as an astrophysicist. He is a popularizer and communicator of science, and has worked in a variety of pharmaceutical organizations (small molecule and biologics), medical device organizations, and within hospitals, clinics, and emergent care centers bringing better healthcare to the end user (i.e., the patients!).