Gene Therapies Present Great Potential, but Also Ethical and Practicality Challenges

Gene therapies have tremendous potential. They are a short treatment that could have lifelong effects. However, the very expensive therapies have a lot of unknowns and raise a number of ethical and practicality questions.

The US drug pipeline is full of gene therapies, according to Bill Dreitlein, PharmD, BCPS, of the Institute for Clinical and Economic Review (ICER). The leading area is cancer, and overall, there are 23 therapies in active phase 3 development.

A small number of gene therapies have already reached market in Europe, but they have yet to see any real success, according to panelists during a discussion at the ISPOR 22nd Annual International Meeting. Glybera is on the market for more than 1 million euros to treat a rare inherited disorder that can cause severe pancreatitis, but so far, only 1 patient has been treated, according to Adrian Towse, MPhil, MA, of the Office of Health Economics in London.

Dreitlein added that Glybera has faced a lot of difficulties. The manufacturer has actually decided not to renew its marketing authorization because there had been so little uptake with the therapy.

An ICER policy summit that brought together payers and life science companies to discuss gene therapies found that concerns cluster around 3 broad areas: evidence, value, and affordability.

Manufacturers are concerned that they might not receive adequate compensation for the risk of developing gene therapies, while payers fear bankrupting the system. Both manufacturers and payers are concerned with the data available: right now, only short-term data are available and the long-term safety of these therapies, or if they represent a true cure with a long-lasting effect, is unclear.

Still, bluebird bio is very excited about the potential of gene therapies. The company mostly focused on genetic and rare diseases, as well as oncology.

“We really believe in the potential of gene therapies to transform patient lives,” said Clark Paramore, MSPH, of bluebird bio.

He echoed some of the concerns that Dreitlein presented from the ICER summit. While these are supposed to be one-time therapies, they are relatively new, so it’s still not clear what the long-term benefit will be. As a result, Paramore said that bluebird bio believes a value-based model makes sense to pay for gene therapies.

A value-based model or a way to pay over time for gene therapies would help alleviate some of the concerns over the unknowns of how these therapies will actually work, said John Watkins, PharmD MPH BCPS, of Premera Blue Cross.

Not only is whether or not the treatment benefit will wear off over time an issue, but so is something that manufacturers have no control over: what happens if the patient dies early in an unrelated incident?

“What if we spend $1 million on a patient and then they get hit by a bus?” Watkins asked.

Gene therapies are also raising ethical concerns. For instance, will there need to be a prioritization of who gets treated? While there should be special concern for vulnerable populations, a lot of patients who will be treated by gene therapies will fall into that category.

“If we cannot afford to pay for it for everyone, where do we draw the line?” Watkins asked.

On the other hand, gene therapies have some great potential for societal benefits. For instance, they could lead to an increase in worker productivity with people who were too sick to work now cured. They might also alleviate care burdens. Patients who are treated with gene therapies will no longer require a caregiver, who had lost the opportunity to contribute socially and economically while they were providing care to the sick individual, Watkins explained.

He explained that spreading payment out over time fits well with gene therapies, because it allows the payer to stop paying for the therapy if the benefit wears off or the patient dies.

A similar payment strategy has been set up in Italy for Strimvelis, a gene therapy used to treat a very rare disease called ADA-SCID, said Towse. Essentially, Italy has set up a money-back guarantee—the drug has to deliver or the manufacturer doesn’t receive payment. And if the drug stops working, money will be returned. The National Institute for Health and Care Excellence (NICE) in the United Kingdom is now considering Strimvelis.

However, reimbursement has been an issue overall in Europe. Glybera had no reimbursement in place. Imlygic, an advanced melanoma treatment, was approved by NICE.

“The European perspective is that gene therapy is making progress, but its slow,” Towse said.

Moving forward with gene therapies will require buy-in in the United States, said Paramore. Industry will have to lead the way, but payers will have to embrace the innovations and remove barriers, and providers will need to think differently about treating patients, and patients will need to demand the innovation. Even Wall Street will have to change its mindset to focus more on the long term over the short term.

Gene therapies are not the distant future in the United States, according to Dreitlein, who predicted that the United States will see one before the next ISPOR meeting.

“Gene therapies are coming, and they’re going to be expensive, so it’s time to start thinking about them,” he said.