Gene therapies are encouraging and evolving treatment options for profound and debilitating diseases, such as certain cancers, spinal muscular atrophy, hemophilia and sickle cell disease. The treatment has been studied since the 1980s, but it's picked up considerable momentum in the last decade. Like any treatment in its early stages, gene therapy shows a lot of promise, but also a lot of questions.
For this episode of HealthChangers, host Ashley Bach spoke with two members of the Regence pharmacy team: Noelle Redmond, assistant director of clinical pharmacy services, and Danny Wallenslager, pharmacy clinical program director. Both pharmacists talk about the current state of gene therapies and what Regence is doing to ensure covered gene therapies provide a clear net benefit for health plan members.
Listen to the full podcast episode on the player above. Below are some highlights, which have been edited for length and clarity.
AB: What are gene therapies?
DW: Gene therapies introduce genetic material into a patient's cells to treat diseases that are caused by genetic mutations. This field is dynamic, and it's a quickly emerging field that really has offered hope for really rare disease states that, to date, really have not had effective treatment options or no treatment options. And they're offering a potential cure for these disease states, as these treatments really address the root cause of a disease at the genetic level.
Gene therapy can really be broken down into three types. One is gene addition, where we're introducing newer, altered genes into a patient to help fight or prevent a disease. Then we have what's known as gene silencing, or turning off a gene that is producing an unwanted effect. And we have gene correction, which is actually fixing a gene that has a genetic defect within it.
AB: What are some of the questions that still need to be answered about gene therapy?
DW: Right now, we have 14 gene therapies that have been approved by the U.S. Food and Drug Administration. And the disease states that are targeted to date are really rare, or even ultra-rare disease states. And with that comes a host of problems that maybe aren’t as prevalent as a more common condition, like say, high blood pressure, where you have hundreds of thousands of patients with the disease state. In these limited patient populations, it's hard to get a large and robust clinical trial.
So the evidence that we have leading to approval is really based on small patient populations studied within these clinical trials. And these small clinical trials paint the initial picture of treatment efficacy. However, what this isn't really doing is painting a long-term treatment impact, or showing the impact over a broad patient base, as we would get with some of the other disease states for larger or more prevalent disease conditions.
When we're talking about long-term efficacy, that's when you hear people talk about durability. How durable is this therapy over time? Are we losing the impact of this gene therapy as the years go by since a patient has received this therapy?
The other elephant in the room when you think about gene therapies is the price tag. Right now, we have gene therapies that range in price from $240,000 for certain cancers, to more than $4 million for ultra-rare disease states. And this is something that the industry at large is grappling with. This is from payers to manufacturers to industry experts like the Institute for Clinical and Economic Review, are all brainstorming, how do we pay for these? How do we make sure this is sustainable? How can patients continue to have access to these ultra-rare, potentially curative game-changing therapies? All parties are going to have to collaborate to ensure that these treatments are available, and they're at a price point that individuals and employers can afford.
The other thing to really be mindful of is the uptake on gene therapy right now, which is probably lower than anticipated. Patients are balancing quite a few aspects when they’re thinking about gene therapy. You're asking someone to genetically alter their body, and people have strong feelings about that. I think you've seen some of the folks who say, “I absolutely want to do this,” are people who have enrolled in clinical trials. And then you're left with patients who are questioning, “do I want to do this? Do I want to wait and see?” Some folks are wondering, is there going to be something that is more effective in the future or better tolerated. This isn't a one size fits all that everybody's going to take this. There's a lot of personal consideration, and everybody's going to be different.
AB: What is the pipeline for future gene therapies?
DW: The pipeline is robust. There are about 80 to 85 gene therapies that are expected to receive FDA approval by 2032, and some of the conditions being studied are much more common than what we've seen. We're seeing trials and gene therapies being studied in Parkinson's disease, coronary artery disease, osteoarthritis and even urinary tract infections. And as we have many more common conditions coming into play, the question that remains to be seen is, how are these going to be priced? Are these going to be priced at the ultra-high price tag that's associated with the historical gene therapies? Or are these going to be priced more in parity with other treatment modalities already used to treat those conditions?
AB: Noelle, how does Regence review gene therapies to ensure they have a health benefit for our members?
NM: Any individual requests from a specific member for coverage for gene therapy is routed through our pharmacy and medical teams for evaluation against our coverage policies. Those coverage policies are developed under the very careful direction of our pharmacy and therapeutics committee. This committee is comprised of independently practicing physicians and other health care providers who are outside of Regence. The rationale for these policies is grounded in an extremely deep review of all currently available, published scientific evidence to ensure that therapies, including gene therapies, provide a clear net health benefit for our members.
As part of this process, we do all sorts of other things too. We seek external expert opinion; we review standards of care and treatment guidelines; we evaluate treatment options; we review practical considerations and health equity considerations – all of this to ensure alignment with our humanistic and holistic approach to drug coverage.
AB: How does Regence’s approach to reviewing gene therapies connect to our pharmacy team’s larger mission?
NM: We really want to ensure that our members have access to the right medication at the right time; and we want that medication to be effective and safe for them. And we have to remind ourselves that the least effective medication is the one that a member cannot afford, right? So then they don't take it. So, by doing this deep review of not only the science, but also the context in which we operate, the context in which that provider is prescribing that medication, the context in which that patient is living, we can help align all of that to ensure right patient, right drug, right time.
AB: How does Regence determine if a gene therapy is medically necessary?
NM: Gene therapies are covered when scientific evidence supports clinically meaningful health outcomes and the durability of that effect supports cost effectiveness. When the price point of gene therapies are at this one-time, significant cost, does the effect of that medication ultimately justify that cost? If there are equally safe and effective treatment options that are more cost effective, the gene therapy might be considered not medically necessary and therefore not covered. If the scientific evidence does not demonstrate an improvement in health outcomes, the gene therapy might be considered investigational, regardless of FDA approval status.
When we talk about net health outcome, what are we really talking about? We're talking about things like your functions improved, your quality of life has improved. We've prevented progression of a disease. Disability has been reduced. We've reduced mortality. So those are the type of things we're looking at to ensure that the drug is not only going to be effective for the patient, but it's going to be worth the cost and hopefully pan out from a total cost of care perspective and an overall treatment effectiveness perspective.
AB: What is an example of a gene therapy that Regence approved, and what was our process for that approval?
NM: We recently approved coverage for two different gene therapy treatments for sickle cell disease, Lyfgenia and Casgevy. Sickle cell disease is a rare genetic disorder that can lead to extreme pain, organ damage and stroke. There's an estimated 100,000 people in the United States living with this disorder, and it primarily affects Black patients. Some medications exist to help treat the symptoms of sickle cell disease, but they don't slow its progression. They don't treat the underlying disease. They're purely just symptomatic treatment. Bone marrow transplants offer a potential curative option, but they're really only available for the handful of patients that meet criteria to have them and have a matched stem cell donor.
These gene therapies for sickle cell disease are super cool, because they present a potentially curative option in a broader pool of patients. In the scientific evidence, both of these therapies resulted in near zero sickle cell symptoms up to 24 months. So patients had less crises, basically no hospitalizations, and that is really unheard of in this disease state. This may represent a curative option, eventually.
Both of these therapies received FDA approval in December of 2023. For the months leading up to that approval, and directly after, our clinical teams thoroughly reviewed all of the available clinical evidence, reached out for expert opinion, looked at all of the practical considerations and ultimately brought our coverage recommendations through our pharmacy and therapeutics committee.
We ultimately landed that for certain patients with sickle cell disease -- with severe disease -- these therapies really do represent a cost-effective treatment option and potential cure with data supporting very clinically meaningful outcomes. We have a coverage policy that identifies that select group of patients and we can facilitate coverage for them.
AB: What does the future hold for gene therapies long-term?
NM: I do believe that gene therapies really represent a leap forward in the evolution of medicine. I mean, we've seen it historically -- from the invention of penicillin because of mold growing on a plate, to small molecule drugs to generic drugs to biologic or big molecule drugs, to immunotherapies, to now, gene therapies. I'm very hopeful that this evolution will be game changing for humanity. That being said, as described earlier, there are a lot of unknowns, and I think because of that, part of our role is to help be a protection and a safety net for our members to ultimately ensure that access and affordability remain tantamount to our mission, so that we are in alignment to provide safe and effective therapies in an affordable manner.