The gene therapy sector isn’t just growing, it’s sprinting. This newer realm of biopharma is rewriting the rules of science and medicine, with novel therapies correcting genes to address complex disorders with few other treatment options. The approach sounds like science fiction, but it’s real life, and it’s impossible not to be excited about the possibilities.
In recent years, we’ve seen an increase in cell and gene therapy drugs, and the next wave is ready for approvals. However, there are persistent challenges to address before gene therapies can trailblaze the clinical landscape.
While the technology has the potential to save lives, costs are often sky-high. Some of the latest FDA-approved therapies like Roctavian, Zynteglo, Skysona, Hemgenix, and more recently Zevaskyn come in at 2.5 to 3.5 million dollars, per dose. In some cases, these therapies have been pulled from the market because of pricing pushback (e.g., Skysona in EU and Zynteglo in Germany) (1,2).
What can we do to address this barrier to groundbreaking care, and fully deliver on the promise of gene therapy?
High gene therapy costs: How do they affect access?
Despite the high price tag of gene therapy treatments, they could be a deal in disguise. In some cases, it might be possible for a single dose to replace a lifetime of medicine that, cumulatively, comes at a much higher cost. For example, a $3.5 million single dose can replace a lifetime of traditional treatment costing up to $20 million for Hemophilia B patients (3).
So, when it comes to access, what’s the catch? In summary, payers and healthcare systems aren’t built to handle such steep prices at a large scale in a short timeframe, even if the large expense ultimately leads to saved lives, and money (4). With pricing already presenting a hurdle for existing therapies treating a small number of conditions, it becomes an even greater challenge when talking about making treatments widely accessible to all the people who need them.
Developing gene therapies for rare diseases can come at a high cost, and the patient population— it’s tiny. This disparity means there’s less financial incentive to commercialize treatments despite a great need. Something has to change.
Innovative cost models help gene therapies reach more patients
Thankfully, a shift towards more creative strategies for gene therapy pricing is underway. Many countries have launched programs to establish best practices and early access programs for easier access for viral vector-based therapies, setting a path for others to follow and helping patients get treatments at discounted prices.
Some EU countries are also exploring pay-for-performance (P4P) models, where payment is tied to patient outcome with full reimbursement only with positive results. This bold, data-driven approach is minimizing cost risks while helping to generate more clinical evidence and advance therapies in the market. Italy and Germany are among the frontrunners in these efforts, accelerating innovative P4P programs that could reshape how we think about drug pricing and long-term value (5).
Additionally to P4P, other strategies are being explored, such as the “Netflix model”. Under this approach, a company or government pays a fixed monthly or annual subscription fee to ensure access to gene therapies for employes or citizens, should they need them.
However, addressing the cost barrier is only part of the solution. Significant accessibility challenges remain, marked by large disparities not only between developed and underdeveloped countries, but also within the Europe itself. Some nations, such as Germany, Italy and France, benefit from strong manufacturing capabilities. Other countries, like Malta and Cyprus, have minimal to no local production infrastructure, which further hinders equitable access to gene therapies.
What are key cost drivers of gene therapies?
Innovative payment and reimbursement models are a step in the right direction, but they don’t solve gene therapy’s pricing problem completely. To holistically lower costs and increase access, we need to look at how viral vector-based treatments are made ― and innovate to make the process less expensive and more successful.
A 2021 study estimated that the R&D investment for new medicines, factoring in the cost of failure, can climb into the hundreds of millions (adjusted to 2019 prices) (6). Although manufacturing costs might not come in quite as high, advancements to this part of the process can help to make treatments more accessible.
One of the biggest factors affecting viral vector manufacturing costs is the amount of product needed for a dose compared to the total quantity produced. For example, in one Phase 3 clinical trial, only 2% of the manufactured product was administered to the patient (7). The rest of the material is used for analytical testing, comparability studies, assay controls, stability testing, device (dead volume) losses, and more. Optimizing analytics and stability testing methods would help to reduce overall manufacturing demands or allow for more doses per batch, both of which can help decrease cost.
Another challenge is the fact that viral vector manufacturing still relies on platforms originally designed for monoclonal antibodies (mAbs) and recombinant proteins. These technologies can get the job done, but they aren’t purpose-built to meet the unique needs of viral vector manufacturing. If we want gene therapy to be truly transformative, solutions providers must focus on developing scalable, sustainable and accessible solutions. Purpose-built platforms for viral vectors would be a game changer.
Solutions providers can play a key role in reducing gene therapy costs
Solution and technology providers are constantly pushing the boundaries of what’s possible in therapeutic manufacturing, as drug developers seek higher performing processes. Closing the gap and quickly building the right tools for viral vector manufacturing can only be achieved through collaboration between these two key stakeholders.
Using technologies specially designed for viral vector-based therapies can boost productivity, increase recovery rates, and, in turn, decrease cost per dose. And keeping regulatory experts in the loop through this process ensures these innovations will comply with stringent standards to allow for more seamless approvals.
Examining improvements in the viral vector process
When we look at the manufacturing process for a viral vector, such as adeno-associated virus (AAV) or lentivirus (LV), the process can usually be broken into two parts: the upstream process (USP) and the downstream process (DSP).
USP productivity can be maximized through bioprocess development, cell line optimization, plasmids and transfection reagent optimization, and, in some cases, the use of stable cell lines. To increase DSP yield, the best approach is to focus on process optimization and improved recovery at every step of the process.
In the case of AAV manufacturing, for example, DSP recovery is often around 25% to 30%, with a few processes achieving up to 50%. Therefore, in a worst-case scenario (25% yield), even with all possible purification improvements ― such as better affinity ligands and the latest innovative solutions ― we can maybe expect to increase yield to 80%. This boost delivering approximately 3 times the yield would probably cut the cost per dose in half. Is that enough savings to drive better access to critical treatments? Probably not.
Looking to upstream productivity for economic viability
Most experts agree, to make gene therapy truly accessible, we need a 10 to 100 times improvement in yield. How do we go from three times improvement to closer to 100 times increase in yield?
To achieve this improvement in yield, we need to work on the USP, using better plasmids and transfection reagents, process intensification, and stable producer cell lines. We can also look to engineer cell lines to excrete AAV and improve the full to empty ratio out of the cell and the infectious titer. USP optimization is the real lever that can transform the costs of viral vector-based gene therapies to help make them more accessible.
Increasing USP productivity can influence cost per dose in many ways. It could drive more doses per batch with fewer batches required for a target quantity of doses and more patients treated per run. Better productivity could also mean less starting material is needed, along with an overall reduction in labor demands and operational expenses (OPEX). Alternatively, the same number of batches could be run but in a smaller bioreactor with fewer skids, a reduction in consumables cost and capital expenditure (CAPEX) investment, and a smaller manufacturing footprint.
Gene therapy developers should keep viral vector scalability in mind early on
In the fast-paced world of gene therapy development, it’s easy to get caught up in the day-to-day challenges and overlook the fact that full-scale manufacture could be on the radar in the future. As we’ve seen before, a process may work in the lab but not necessarily at scale. If scalability isn’t considered in the process from the start, it can lead to costly, inefficient, and hard-to-manufacture therapies down the line.
But when scalability is top of mind early on, developers can make smarter technology choices from the beginning. There’s room between clinical phases to make process adjustments but starting with something that mirrors the final manufacturing setup creates a substantial volume of historical data showing process consistency and reproducibility, helping pave the way to regulatory success.
To build the most cost-efficient process, it’s not enough to pick just the right tools, you must optimize every stage; from screening and testing to scaling and redefining, every decision matters. The closer your early-stage process is to your commercial process, the more confident you can be in its performance, reliability, and long-term viability.
Balancing cell line productivity, yield, and purity standards
Studies have shown that screening transfection reagents and cell culture media options can boost viral vector yield and drive overall costs down (8).Some companies are taking it a step further by looking to cell line engineering or stable cell line establishment to improve their process (9). Recent examples have shown us that improving USP productivity by 50% decreases manufacturing costs by 33% (10).
Tools like cost modelling can help shed light on the impact of specific optimization efforts on the cost per batch or dose, or even just find the main cost drivers of the process (11). By identifying the biggest cost drivers, we can focus on making changes where they’ll have the most impact.
Although increasing USP productivity means more doses and greater efficiencies, it’s not without its drawbacks. Higher yield often brings more impurities, which can complicate the DSP. This shift can add more purification steps, larger equipment, and ultimately more downstream processing costs. While more USP yield is valuable, it must be carefully balanced against the DSP constraints to ensure a true cost decrease on gene therapies.
Process intensification, driving cost efficiency in viral vector manufacturing
Process intensification (PI) is another strategy that can help to optimize the cost per dose (12). PI minimizes sources of waste, usually attributed to the following categories: transportation, inventory, motion, waiting, overprocessing, overproduction, and defects. Some business drivers for process intensification are cost of production, footprint reduction, manufacturing flexibility, time to market, facility use, scalability, and ease of use.
PI was recently used during the development of the ChAdOx-1 chimpanzee adenovirus‐vectored SARS‐CoV‐2 vaccine (13). In this work, we saw two examples of PI having a direct impact on cost without affecting product quality (13). The optimization of the USP with a lower multiplicity of infection (MOI) led to a reduced virus seed (1 order of magnitude) while keeping the same productivity, critical quality attributes (CQAs), and production time. On the DSP side, the team demonstrated that a pre-established process contained an unnecessary step for this particular virus purification. Removing the unnecessary step before chromatography, while keeping similar CQAs and yield, allowed for process time to be shortened.
As the industry moves towards innovative platforms to decrease time to market and costs, it’s essential to couple these efforts with process intensification. For every new molecule developed, processes should be reassessed to make sure they’re as cost efficient as possible.
Manufacturing innovation, a tool for improving patient access to gene therapies
Can we really decrease the cost per dose of gene therapies? Absolutely, but it’s going to take a collaborative effort.
Gene therapy developers need to push the boundaries of USP, aiming for 10 to 100 times improvements through innovations like cell line and capsid engineering. Scientists should also think about manufacturability from day one, choosing platforms that facilitate scale-up later.
At the same time, technology providers need to deliver smarter manufacturing and characterization tools to streamline processes and boost efficiency. PI and optimization must start early, right at the research stage.
And finally, health authorities, governments and manufacturers should rethink how treatments are priced and reimbursed to make them truly accessible (14).
Real industry innovation isn’t just about better science; it’s about shifting the entire cost model to make these lifesaving treatments accessible for the people who need them most.
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