What’s in store for cell and gene therapy?

Cell therapies have come a long way since the first successful stem cell transplant in 1972. Likewise, gene therapies have advanced significantly since scientists first demonstrated the potential for a modified virus to introduce a functional gene into a four-year-old girl who a lacked a critical enzyme in her immune cells. A small but growing number of such therapies have now been approved by global regulators for use in patients, and more are entering the development pipeline all the time. Nevertheless, challenges remain that are holding the therapy area back from widespread adoption. How can they be successfully overcome?

Over the past few years, we have seen a rise in the number of cell & gene therapies (C&GTs) approved for use in patients.

For instance, onasemnogene abeparvovec (Zolgensma) was approved by the US Food & Drug Administration (FDA) in May 2019 and the European Medicines Agency (EMA) in May 2020[1]. This is a gene therapy for the treatment of spinal muscular atrophy (SMA) in people with clinical symptoms of SMA type 1 or who have two or three copies of the SMN2 gene. In May 2019, the EMA approved another gene therapy, betibeglogene autotemcel (Zynteglo), for treating beta thalassemia in people twelve years of age and older[2]. Also, in recent years, five new T-cell therapies utilizing chimeric antigen receptors (CAR-T) have been added to the armamentarium for hematological cancers.

This is exciting news for many patients living with serious conditions, such as cancers and rare genetic disorders. However, even now, C&GTs are a long way from being established treatment modalities. A number of challenges are on the horizon that need to be addressed if the area is to reach its full potential.

What’s hindering progress?

Several factors are restricting the advancement of this sector as a whole and holding up innovation. Given the complexities and cost of C&GT development, it is still very challenging to find therapeutic candidates capable of providing long-lasting benefit, if not outright cures. In an ideal world, a single or just two administrations would lead to a prolonged or even permanent improvement in health. For many of these agents, the benefit does not live up to this ideal.

The next challenge is safety. There are safety risks inherent to all drug candidates. However, C&GTs are still novel treatment areas and, as therapies with potentially long-lasting effects, risk mitigation is especially important. Any potential safety issues could be detrimental to C&GT developers given that they are predominantly small companies with limited financial resources.

Another challenge that is hindering success is the issue of logistics. Again, C&GT is a novel treatment, meaning that even in major developed economies, the infrastructure simply isn’t in place to develop the tailored therapy, transport it and administer it to the patient quickly and efficiently. This adds to the cost of many current C&GT products.

C&GTs for cancers come with their own unique challenges. Each cancer has its own unique genetic code and, furthermore, solid tumors are vastly different from hematological malignancies. Hematological malignancies are known to become resistant to cell therapies, and patients can relapse owing to decreased persistence. For solid tumors, the identification of a suitable antigen, overcoming an immunosuppressive tumor microenvironment (TME) and robust trafficking of cell therapies to the tumor site are still formidable challenges.

This means that there is no “magic bullet” therapy capable of tackling all cancers all of the time. Oncolytic C&GT is still in its infancy, particularly when it comes to attacking solid tumors, and there is a long way to go before the treatment replaces existing cancer therapies.

Opportunities to grow

But there is so much excitement and promise in the C&GT arena at the moment. There are lots of potential innovations capable of overcoming many of the challenges facing the sector.

While safety and scalability are still issues that need to be tackled, they are not deterring companies from entering the C&GT space or investors from funding the research. The resistance of malignancies, for example, is being addressed with bi- and tri-specific CAR-Ts that target multiple antigens. Persistence of therapies, meanwhile, is being increased using younger T-cell phenotypes/ memory stem T-cells and “armored” T-cells that express stimulatory cytokines.

By genetically engineering T cells to use logic functions, solid tumor targeting is also expected to improve. In addition, the use of chemokine receptors is being evaluated to help direct CAR-T cells to the tumor, and several strategies, such as cytokine expression and combinations, are being used to modulate the TME.

The development of C&GTs is not the only area where innovation is occurring. The manufacturing of C&GTs and the treatment supply chain are both undergoing a transformation too, thanks to investment by many pharma companies in improving the commercial supply of first- and second-generation products to market. For example, in-vivo gene editing avoids the need for highly complex and time-consuming logistics, speeding up delivery of the treatment to patients.

In addition, as more and more C&GTs are approved for use, the industry is learning from existing development processes. As a result, we are gradually identifying effective platforms and standardized approaches that have the potential to streamline development processes for new therapies in the future. In doing so, we can be more confident of getting effective treatments to the patients who need them.

How to thrive in the present?

In addition to the potential for future growth for C&GTs, there is plenty of opportunity for new therapies to thrive now, provided companies have the market intelligence, expert support and resource to bring their products to market effectively.

Insight into different markets ahead of commercialization is crucial in order to understand what communications, physical support or even price plans will be needed in each geography. This will ensure successful take-up of the therapy by patients and healthcare providers (HCPs). It is also important to explore what additional logistical processes need to be in place in each market to streamline treatment delivery to patients. Some markets are ahead of others – China, for example, has made great strides in the adoption of C&GT and is ahead of the curve in terms of its ability to provide access to treatment for patients.

This in-depth knowledge can only come from having access to experts in each market with the local resources, networks and experience to provide informed and accurate guidance.

This in-depth expertise is something that a strategic partner, like Ashfield Advisory, is well placed to provide. Ashfield Advisory’s expert teams at SmartAnalyst, Putnam, PHMR, Vynamic and STEM Healthcare work with C&GT companies to provide market insight from the earliest stages of drug development, helping to ensure that commercialization is kept front of mind and allowing for a smoother journey to market.

In addition, EmerGENE is an industry-first multidisciplinary team of experts from across Ashfield that is capable of providing a comprehensive suite of services to guide you and your discovery through every stage – from supply chain to successful launch, from medical affairs and market access and value to medical information services and patient support programs.

We can also support companies in developing approaches to track performance and forecasting for their new therapies. This can help them demonstrate value and a return on investment to investors, enabling them to put in place the funding for future therapies.

The future of C&GT

There has been no “Big Bang” for C&GT yet, but that doesn’t mean that there won’t be in the future. New C&GT therapies face challenges on their journey to market and beyond, it is true, but they have so much potential for transforming the treatment of serious diseases that we can expect the development pipeline to grow for the foreseeable future.

For pharma companies to maximize the chance of a successful roll-out of their new therapy, they should consider engaging with a specialist partner. By working with Ashfield Advisory and the EmerGENE network, companies can be confident that they have the support they need to deliver their products effectively to the people who need them most – the patients.