Abstract
When discussing gene and cell therapies, the conversation often centers around issues of affordability, equitable access, manufacturing limitations, and ultimately the conundrum of creating a sustainable business model. There are many obstacles that face the gene and cell therapy market, but we have made significant progress in the last decade with the approval of a range of therapeutics tackling diverse clinical indications across oncology, neuromuscular disease, and inherited blindness. Indications are also expanding as this foundational work can be applied to other tissue regions, but with FDA predicting that there will be raft of new products coming to the market in the next year the payor community is steadfast in its belief that the requisite frameworks are not in place to accommodate new approvals.
The success story of CRISPR and the sickle cell patient Victoria Gray has been well documented of late, but the reality is that for the majority of the patient population afflicted by this disease—who hail from Africa and India—access to this treatment will simply be out of reach. So how do we make the economics work for greater societal benefit? Well, this is a question many policymakers, regulators, payers, and rare disease organizations are constantly grappling with. We do need to reframe the discussion around value as opposed to cost and focus rather on the human cost of not delivering these therapies to patients. We need to balance the financial burden over a lifetime for many of these existing therapies with the one-off cost of a curative therapy. Of course we should never use this word lightly, as we simply do not have the evidence to support guarantees of long term durable response for any gene therapy brought to the market.
Delivery of gene therapies is also a very buoyant field with a range of approaches being investigated outside of traditional viral vectors in order to overcome issues surrounding off target effects and dosage limitations. Extracellular vesicles have the potential to facilitate repeat dosages and open up broader applications across many genetic diseases. Transdermal approaches are also being investigated as a minimally invasive mechanism, but again, both of these approaches come with limitations in scalability and stability, respectively.
CAR T therapy is clearly an exciting field and we have seen transformational effects on patients with certain leukemias, but toxicities still abound and in solid tumors we're still largely in uncharted territory. We still have to figure out the intricacies of how the immune system works and how and when we can manipulate it with precision. The autologous route is a complex, costly, and lengthy process; the biggest cost to the patient of course is time. For some, the “off-the-shelf” approach with allogeneic cells can give patients access in a more timely manner and reduce the number of visits to the clinic, but of course issues still linger around rejection of these cells, so work is ongoing.
For the rare disease community, many of these approaches offer huge hope, but all stakeholders need to figure out how to align incentives and work together in lockstep to make this a reality for patients. We'll need new ideas and a common goal underpinned by AI to help reduce timelines so that patients won't suffer any more than they need to.
