Gene therapies can cure diseases, but they can cost BRL 10 million per dose

Rob Schroeder has spent most of his life having to have regular injections of blood clotting factor to combat the uncontrolled bleeding caused by the genetic disease hemophilia B.

But his life was transformed four years ago when he volunteered to be one of the first patients to undergo a trial of an experimental genetic treatment called Hemgenix.

“Since the treatment, I haven’t had any more bleeding. Nothing. With this treatment I fulfilled my biggest dream,” Schroeder, a pharmaceutical representative from Monclova, Ohio, told the Financial Times.

Last month, the FDA (US agency that regulates food and drugs) approved Hemgenix, developed by CSL Behring and UniQure and administered in a single dose by intravenous infusion.

It is the fifth rare disease genetic treatment to receive the green light from US regulators since 2017, highlighting the potential of this new class of drugs to treat and in some cases cure rare diseases, cancers and other conditions.

Gene therapies, which work by adding a new gene to the body or repairing a mutated gene, can dramatically improve health problems by resolving their original cause, usually through a single treatment. But they are complex drugs that can have dangerous side effects and are sold at extremely high prices.

CSL’s Hemgenix costs US$3.5 million (R$18.5 million) per dose, making it the most expensive drug in the world.

Developed by biotech Bluebird Bio, from Cambridge, Massachusetts, Skysona and Zynteglo, gene therapies against a rare childhood brain disease and a congenital blood disease, are the second and third most expensive drugs on the market, selling for US$ 3 million respectively (R $15.8 million) and $2.8 million (R$14.8 million) a shot.

Health experts warn that the high cost of gene therapies could limit the willingness of public and private insurers to cover them, making them unaffordable for many patients.

With more than 1,000 gene therapies and cell therapies in clinical trials, there is concern that healthcare systems could buckle under the weight of the short-term costs of meeting demand for treatments.

Last year Bluebird Bio withdrew Zynteglo, a single-dose gene therapy for the blood disease thalassemia, from the European market after failing to persuade European governments to match its $1.8 million price tag. millions). The company told analysts that European payers have not developed their approach to gene therapy in a way that values ​​innovation. She described elements of the European system as being “frankly broken” and “unviable” for investment.

With its departure from Europe, Bluebird was forced to reduce its costs, cutting 30% of its staff, and is now investing in sales in the United States, where regulators approved Zynteglo in August.

Miguel Forte is president of the International Society for Cell Therapy and Genetics, a group of clinicians, researchers, and industry partners that support the development of these drugs. He said the withdrawal of an approved treatment was disappointing and that if it were to happen again it would cause “serious concerns”.

“I think a discussion about the affordability of treatments is essential. We need to ensure that these innovative medicines are available to patients, and we also need to continue to learn about them and develop new products.”

In contrast, Zolgensma, Novartis’ gene therapy for spinal muscular atrophy, which was the world’s most expensive drug when it hit the market in 2019, sold well in its early years. Sales were up 36% in 2021 as the Swiss pharmaceutical company expanded its access to Europe and emerging markets. But they fell 15% in the last quarter, something the company attributed to a slowdown, but entered new markets anyway.

Novartis said it did not believe the drop in sales was linked to reports of the deaths of two children who had taken the drug.

Gene therapy products can be expensive, but according to Forte, they bring great benefits to patients and health systems. The unique nature of these healing therapies improves the quality of life for people suffering from rare diseases and can save money in the long run by reducing or eliminating the need for medical treatment, he added.

“If we can’t square the circle around costs and reimbursements, we will fail to provide patients with the right opportunities.”

The biopharmaceutical industry says high prices are needed to cover the cost of developing gene therapies, which run to $5 billion (R$26.5 billion), about five times the cost of traditional medicines. And the markets for these drugs are often small. In addition, complex manufacturing and regulatory processes lead to long wait times before treatments are made available to patients.

Last year, investors and companies invested a record amount of US$ 22.7 billion (R$ 120.1 billion) in cellular, genetic and tissue engineering therapies, against US$ 19.9 billion (R$ 105.3 billion) in billion) a year earlier, according to the Alliance for Regenerative Medicine, a lobby group representing companies large and small.

Sales of genetic and cellular treatments are relatively modest for now, reaching US$4 billion (R$21.2 billion) in 2021, but are forecast to reach US$45 billion (R$238.2 billion) by 2026 with the approval of dozens of other treatments, according to market intelligence firm Evaluate Pharma. But achieving that sales growth depends on the willingness of governments, insurers and other healthcare payers in rich countries to cover the cost of treatments.

Merith Basey, executive director of patient advocacy group Patients For Affordable Drugs Now, said: “Our health care system is not in the financial position to pay the price that pharmaceutical companies are asking for these new drugs, no matter how revolutionary they are.”

“Hemgenix is ​​an innovation that can save the lives of patients who can afford it, but this innovation is of no value to those who cannot afford it.”

Bob Lojewski, CSL’s senior vice president and general manager for North America, said Hemgenix’s $3.5 million price is justified because it is possibly “the most effective treatment in the world” and will generate big savings in the long run. He also said that there will be some discounts for health plans and payers.

“It’s unfortunate that price makes the headlines rather than the safety, efficacy and promise of the therapy,” he said.

According to him, the treatment of patients with hemophilia B throughout their lives implies costs in excess of US$ 20 million (R$ 105.8 billion).

A review by the Institute for Clinical and Economic Review, an independent drug regulatory body, concluded that a $2.96 million (R$15.6 million) million price tag for Hemgenix is ​​justified due to its effectiveness. He said that successfully treated patients appear to be cured, at least for a period of time. But the institute cautioned that there is still considerable uncertainty as to whether the treatment’s success will prove lasting in the long term.

AHIP, a group representing more than 1,300 companies that provide health insurance to 200 million Americans, said its members are not averse to paying for gene therapy drugs as long as they are proven to be effective and cost-effective.

According to the organization, health plans are likely to announce restrictions to ensure that therapies are accessible only to patients for whom they are most suitable. In addition, he said patient co-payments will be common.

“In the case of Hemgenix, there’s a lot going for it. It’s a cure. It’s one dose and it’s over. And it helps a sector of the population, people with hemophilia B, who don’t have many treatment options,” said Sergio Santiviago, of the AHIP.

He said insurers are looking at risk-based payment options to overcome the difficulties of covering expensive treatments that in most cases have not proven to be valid for longer periods. For example, AHIP members agreed to a Zynteglo coverage scheme whereby Bluebird Bio will have to reimburse 80% of the costs if patients again need blood transfusions less than two years after treatment.

But, according to Santiviago, the picture is complicated when large numbers of patients can be entitled to treatments that cost millions of dollars, especially if there is no convincing evidence of their effectiveness.

A major trial is on the horizon with the expected 2023 US approval of a sickle cell gene therapy developed by Vertex Pharmaceuticals and Crispr Therapeutics. About 100,000 Americans have sickle cell anemia, versus just 30,000 who have hemophilia B.

A study evaluating the impact of gene therapies on US state budgets, published last year in the journal Jama Pediatrics, concluded that an effective gene therapy for sickle cell anemia would end cost problems for many Medicaid insurance plans.

“Highly priced treatments get a lot of attention, but from a payers’ point of view, what usually matters most is the number of patients,” said Patrick DeMartino, a physician who specializes in treating children with blood disorders and co- author of the Jama Pediatrics study.

“From a patient access and advocacy point of view, if there was a delay in accessing treatment due to a problem with payer restrictions, it would be a public relations nightmare. It would hurt people, but it would also be very damaging to the payer’s image. .”