There continues to be significant interest in the concept of gene therapy. In terms of its impact on medication delivery and medication budgets gene replacement therapy is the method that is the most likely to make a near term impact. With gene replacement therapy a missing or nonworking gene is replaced with a new working copy of the gene. The new gene is created in a laboratory and then incorporated into a delivery vector. For patients with a variety of monogenic diseases, adeno-associated virus (AAV) is the most common and efficient vector to transfer new genes into patients. The AAV vector carries the gene into the nucleus of target cells where the new gene then can become part of the cell’s DNA, or it may stay separate. In either case, the new gene starts to make the protein that’s missing or under supplied. When the vector has completed delivery and is not needed, it is simply eliminated from the body.
Currently, three gene replacement therapies have reached the market and are commercially available and include:
- tisagenlecleucel (Kymriah, Novartis), currently approved for pediatric & young adult patients with relapsed/refractory B-cell precursor acute lymphocytic leukemia & adults with relapsed/refractory large B-cell lymphoma
- axicabtagene ciloleucel (Yescarta, Kite/Gilead), currently approved in adults with relapsed/refractory diffuse large B-cell lymphoma
- voretigene neparvovec-rzyl (Luxturna, Spark), currently approved to treat biallelic RPE65 mutation–associated retinal dystrophy
While there are only three marketed therapies, there are over 700 clinical trials involving gene therapy that are ongoing. Last year $8.2 billion was dedicated to gene therapy research overall which is a 39% increase in funding over the previous year, highlighting the rapid increase in interest.
Along with the excitement regarding the clinical impact that gene therapy can have, there remains a plethora of clinical and safety questions yet to be answered as well as an overarching concern about how the costs of these new therapies will be paid. Current therapy costs are significant with ranges between $375K – $850K. However, these numbers pale in comparison to projections for the soon to be released spinal muscular atrophy gene therapy where the manufacturer is indicating the therapy may provide good value at a price in the $4-$5M range.
These types of prices most definitely do not fit into current payer models and payers are scrambling to find coverage solutions that work for gene therapies. While these therapies may represent significant savings in the long run by eliminating high cost diseases, payers must still come up with the large up-front cash outlay and to attain the ultimate long-term savings, the patient must stay on the payer plan. With such high costs, payers are rightly concerned about putting these types of dollars at risk. Some payment options currently under consideration include:
- Carve-outs or High-Risk Pools: In this case, these extraordinarily high cost patients would be “carved-out” of current insurance pools and placed into high risk pools that would be subsidized by government funding. Certainly, a great option for payers and patients but begs the question of where the government funding would come from?
- Milestone-based contracts. This approach would entail specified payment end points, which would be tied to specific outcomes. Milestone contracts generally would be a shorter term at 12-24 months and while they can soften the payment blow somewhat they still can involve high cost payments.
- Performance-based annuities. This approach further spreads out payments over a longer time period such as five years thus reducing the pressure and risk of large up-front payments. Typically this approach would also include outcome-based payments.
There are obviously many great challenges with the emerging field of gene therapy but with any situation where great challenges are present there are also great opportunities and it will be important for pharmacy to take a leading role in helping to design the construct, use and payment plans for this new therapy.