Gene Therapy Performance Guarantees Will “Improve Access”

Gene therapies are not inexpensive to develop and yet manufacturers still must negotiate prices that reflect what the market will bear. This was reflected in the United Kingdom recently when, in a draft decision, the National Institute for Health and Care Excellence recommended against use of Hemgenix (etranacogene dezaparvovec), a gene therapy for hemophilia B, partly because of its cost but also because of uncertainties about its effectiveness.

In the United States, the drug has a list price of $3.5 million, which is why individuals in the hemophilia community were relieved to see manufacturers of Hemgenix and Roctavian (valoctocogene roxaparvovec, $2.9 million), a gene therapy for hemophilia A, offer payers “warranties” that allow partial or full reimbursement if patients fail to respond to these therapies.

Such terms have encouraged payers to allow access to Hemgenix and Roctavian for patients.

Managed Healthcare Executive^® (MHE) spoke to Joe Pugliese, president and CEO of the Hemophilia Alliance, a patient advocacy group, about these developments.

MHE: How does the Hemophilia Alliance view these warranties for gene therapy?

Joe Pugliese, president and CEO of Hemophilia Alliance

Credit: Hemophilia Alliance

Pugliese: These will absolutely improve access. We don’t want to take credit for it, but we have been in conversations with gene therapy manufacturers in our space for at least the past 3 or more years. And our position has always been that they have to warranty the product, because insurers would be reluctant to pay $3 million for a product that in some cases is not going to work, right?

Not every patient is going to be successfully treated with these products, so we have felt for years that this was the most appropriate way to bring these products to market. To their credit, our manufacturing partners have agreed that this is the best way to move forward.

MHE: Have warranties for therapy failure been offered for other Hemophilia products?

Pugliese: We have a small group at the Alliance whose focus is on talking to payers, brokers, and others on that side of the business, not just about gene therapy, but about all blood clotting products. But these others may cost $20,000 or $30,000 per month, or potentially more, and you know immediately whether the patient’s responding or not, which is very different from a $3 million cost. If patients are properly screened, counseled, and followed at a federally supported hemophilia treatment center, outcomes will be more reliable, but durability of the treatments will remain an uncertainty.

MHE: The average patient may stay with an insurer for just four years, so why should they cover the multimillion-dollar cost of a lifetime “cure”?

Pugliese: I always think it's funny when payers bring up that discussion, because they're always the ones paying for the procedure, but never the beneficiary of some other insurance company already having paid for it. Statistically, that seems unlikely, right?

The whole idea behind insurance is for us to collectively pay for everybody's health care. I think we're going to need to come up with some creative solutions, particularly for smaller insurance pools, where your self-funded employer may have just 100 employees. I think a big part of it is exactly what BioMarin (Roctavian) and CSL Behring (Hemgenix) are doing, and that’s putting a warranty on the effectiveness of the product.

MHE: The clinical data on gene therapy are limited to a handful of studies with only moderate enrollment. How important are patient adherence and tracking real-world outcomes?

Pugliese: What happens in the 6 to 9 months post infusion of the gene therapy is critical. Patients owe it to the patients who come after them to do everything they can to ensure a successful outcome.

Reliable screening is essential to find the patients most suited for these gene therapies, and everyone's going to do the best job of that they can, but that doesn't guarantee you're going to have a successful outcome.

MHE: Prevention and treatment of adeno-associated viral vector transaminitis is essential to avoid treatment failure, and this requires post-infusion assessments up to several times a week for the first half year or longer. There’s also liver health and hemophilia-related complications to worry about. How is all this affecting patients’ thinking?

Pugliese: My advice to patients is don't let anyone else make this decision for you. If you take one of these therapies today and you don't respond well to it, as long as the next gene therapy product has an adeno-associated virus base, you're going to be excluded from trying it again.

Some of them I've talked to have said, “Well, I kind of want to see how it goes, and I know there are other gene therapy products in the pipeline. Maybe I'll wait and see how they compare.”

MHE: Yet, patients must be very excited about the potential for a hemophilia cure.

Pugliese: In hemophilia we have been talking about the promise of gene therapy for at least the last 25 years. I mean, this was going to be the cure. When they work as advertised, they certainly are a vast improvement, with the potential to offer you a bleed-free life for years.

At the same time, we've been blessed with a plethora of ever-more effective or more convenient non-gene therapy bleeding control products—products that have a longer half-life, have different mechanisms of action, and are easier to use. And there's more coming. It's really an exciting time.