On 22 November, the US Food and Drug Administration (FDA) approved the first gene therapy for the genetic blood-clotting disorder haemophilia B–a one-time treatment that costs US$3.5 million.
Hemgenix–developed by the pharmaceutical company CSL Behring, based in King of Prussia, Pennsylvania–uses a modified virus to deliver a gene to the recipient’s liver cells. The gene codes for factor IX, a protein that is involved in blood clotting. People with the disease cannot produce it.
Clinical trials data show that a single dose of Hemgenix can provide moderate to severe haemophilia patients with adequate protection against uncontrolled bleeding for up to eight years.
But the treatment’s high price makes it the most expensive drug on the planet. It seems to be effective, but gene-replacement therapies for haemophilia are still not available.
CSL Behring believes the cost is justified. The company stated that Hemgenix, even at a price of $3.5 million, could save the US $5 million to $5.8million per person treated. This is due to its proven effectiveness in decreasing or eliminating the need for frequent injections of factor VIII. People with haemophilia B (who account for 15% of haemophilia cases) are currently given factor IX once or twice a week. People with the disease do not have enough of the protein to form blood clots. Uncontrolled bleeding can lead to serious complications.
” “Living with haemophilia depends on where one was born,” Glenn Pierce, vice president of the World Federation of Hemophilia, Montreal, Canada. “In the US, the treatment of an adult with haemophilia B averages $700,000-800,000 per year. Hemgenix’s high price will be paid off in a short time and, assuming it lasts .
But scientists are concerned that the cost would be prohibitive in low- and mid-income countries where most haemophilia sufferers live and where supply of factor IX and treatments is often limited. “The most vulnerable people will be the ones who can least afford to pay for new technologies like gene therapy. Pierce says that we cannot leave the majority behind. CSL Behring declined any comment beyond its public statement on the drug’s price.
The latest clinical trial of Hemgenix, which included 54 people with haemophilia 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. Andrew Nash, chief scientific officer at CSL Behring, says that patients make factor IX very quickly. In seven to eight months, almost all patients had stabilized their level.
Even the lowest response in the clinical trial, a 10% increase in factor IX levels, is sufficient to prevent spontaneous bleeding, researchers say. But patients might require top-up prophylaxis treatments after injuries, or if they’re having major surgery and their factor IX levels are less than 50%.
“If you’re in the 10-40% range, you could still get a problem with major trauma or surgery. You can forget about haemophilia,” Edward Tuddenham, a consultant haematologist from University College London and part the research group that created the viral vector that CSL Behring licensed.
Tuddenham showed that gene therapies are a viable and long-lasting treatment in an eight-year-long follow-up study on a similar drug for haemophilia A.
” The approval of Hemgenix marks a significant milestone on the path to a cure. It appears likely that some recipients will be cured for many more years,” says Pierce.
The FDA’s approval highlights the difficulties in developing gene therapies for haemophilia. Only 15% of people with haemophilia have haemophilia B. Most people with haemophilia A have a genetic disorder called factor VIII. This is a defect in a blood-clotting protein called factor VIII. It is encoded by a different genome.
Finding a gene therapy that works for haemophilia has been difficult. A greater increase in factor VIII production is required to achieve a therapeutic effect. Some clinical trial participants have shown strong immune responses when exposed to the viral vector.
” In haemophilia, there is an evident waning off with the time and [the gene expression may only last for 8 years],” says Michael Makris who studies haemostasis, thrombosis, and haemostasis at Sheffield University in the UK. “Adeno-associated virus gene therapy is when you make antibodies to the AAV vector. .”
On 24 August, the European Medicine Agency approved a gene therapy for haemophilia A by BioMarin Pharmaceutical, based in San Rafael, California. After rejecting their initial application, the FDA is now considering BioMarin’s resubmission.
“Gene therapy is a promising and exciting option, but it should not be taken lightly,” says Leonard Valentino. He is a former haemotologist and chief executive of the US National Hemophilia Foundation. “It can be life-changing, and there can be both positive and negative consequences.”
This article is reproduced with permission and was first published on December 6 2022.