$3.5 million hemophilia gene therapy is the most expensive drug in the world

On November 22, the U.S. Food and Drug Administration (FDA) approved the first gene therapy for the genetic blood-clotting disorder hemophilia B — a one-time treatment that costs $3.5 million.

Hemgenix — developed by pharmaceutical company CSL Behring, based in King of Prussia, Pennsylvania — uses a modified virus to deliver a gene into the recipient’s liver cells. The gene codes for a protein involved in blood clotting called factor IX, which people with the disease cannot produce.

Clinical study data suggest that a single dose of Hemgenix provides adequate protection against uncontrolled bleeding for eight years and possibly longer in people with moderate to severe haemophilia.

But the high price of the treatment makes it the most expensive drug in the world. And while it appears to be effective, gene replacement therapies for the most common form of hemophilia remain elusive.

Significant savings

CSL Behring believes the costs are justified. In a statement, the company said that even at a cost of $3.5 million, Hemgenix could save the US healthcare system $5 million to $5.8 million per person treated because it has been shown to be effective in eliminating the need for regular factor injections reduce or eliminate IX. People with hemophilia B (which account for 15% of hemophilia cases) are currently given Factor IX once or twice a week. The protein is needed for blood clots to form, but people with the disease lack the gene needed to make it in sufficient amounts. If left untreated, the condition causes uncontrolled bleeding, which can be life-threatening.

“Living with hemophilia is all about where you were born,” says Glenn Pierce, vice president of the World Federation of Hemophilia in Montreal, Canada. “In the United States, it costs an average of $700,000 to $800,000 per year to treat an adult with hemophilia B. Hemgenix’s high price will pay for itself in a relatively short period of time, provided it holds.”

However, scientists fear the price would be unaffordable in low- and middle-income countries, where most people with hemophilia live and where treatment and factor IX coverage is often inadequate. “As new technologies such as gene therapy emerge, those who would benefit the most can afford the least. We can’t leave most of the world behind,” Pierce said. CSL Behring declined to comment on the drug’s pricing beyond its public statement.

Promising results

The most recent clinical trial of Hemgenix, involving 54 people with hemophilia B, reported a 54% reduction in the number of bleeding episodes per year, and 94% of participants discontinued any prophylactic therapy within two years of receiving the single dose. “Patients begin producing factor IX very quickly…7 to eight months after a single dose, factor IX levels had stabilized in almost all patients,” said Andrew Nash, CSL Behring’s chief scientific officer.

Even the lowest response in the clinical trial, a 10 percent increase in factor IX levels, is enough to prevent spontaneous bleeding, the researchers say. However, patients may need additional prophylactic treatment after injury or if they are undergoing major surgery and their factor IX levels are less than 50%.

“If you’re in the 10-40% range, you could still have a problem with major trauma or surgery. But hemophilia is all but forgettable,” says Edward Tuddenham, consultant hematologist at University College London and part of the research group that developed the viral vector licensed from CSL Behring.

In an eight-year follow-up study of a clinical trial of a similar drug for hemophilia B, Tuddenham and his colleagues showed that there is good reason to consider gene therapy as a stable and long-lasting treatment.

“The approval of Hemgenix is ​​an important milestone on the road to a cure, and it seems likely that some recipients will actually be cured for many years,” says Pierce.

immunity problems

The FDA approval highlights the difficulties in finding gene therapy development for hemophilia in general. Only 15% of people with hemophilia have hemophilia B. Most have hemophilia A — a genetic condition caused by a deficiency in another blood-clotting protein called factor VIII, which is encoded by a different gene.

The search for an effective gene therapy for hemophilia A has proved difficult, as greater increases in factor VIII production are required to achieve a good therapeutic effect, and some participants in clinical trials have shown strong immune responses to the viral vector , which is used to transfer the gene.

“In hemophilia A there is an apparent decline over time and [the gene expression] possibly just eight years,” says Michael Makris, who studies haemostasis and thrombosis at Sheffield University, UK. “Once you’ve had adeno-associated viral gene therapy, you make antibodies against the AAV vector so you can’t have it again.”

On August 24, the European Medicines Agency approved a gene therapy for hemophilia A from BioMarin Pharmaceutical, based in San Rafael, California. After the first application was denied, the FDA is now considering resubmitting BioMarin.

“Gene therapy, while exciting and promising, should not be taken lightly,” says Leonard Valentino, a former hematologist who is executive director of the US National Hemophilia Foundation in New York City. “It’s a potentially life-changing decision, and every life-changing decision can have both positive and negative implications.”

This article is reproduced with permission and was first published on December 6, 2022.