The FDA has approved the first hemophilia B gene therapy, a one-time treatment that addresses the root cause of this inherited disease and potentially eliminates the need for regular infusions that patients currently receive to prevent bleeding episodes. Removing this economic burden from patients and the health care system comes with a premium price: $3.5 million per infusion.
The regulatory approval, announced late Tuesday, for the CSL Behring therapy covers adults who receive prophylactic infusions or have a history of life-threatening bleeding, as well as those who have recurrent and serious episodes of spontaneous bleeding. The gene therapy, known in its development as etranacogene dezaparvovec, will be marketed under the name “Hemgenix”.
Hemophilia is a blood clotting disorder in which genetic mutations result in abnormally low levels of clotting proteins. The two most common types of the disease are hemophilia A and hemophilia B; the latter is the less common of the two, accounting for about 15 percent of hemophilia patients, according to the FDA. It is caused by a mutation in the gene that codes for a blood clotting protein called factor IX (FIX). Although many women can be carriers of the disease, they usually have no symptoms. Most of the patients who have hemophilia B and develop symptoms are men. The product label states that the therapy is not intended for use in women.
Without sufficient levels of clotting proteins, hemophiliacs are susceptible to bleeding episodes. Standard treatment for hemophilia B involves regular infusions of FIX to replace the clotting protein that patients are missing. CSL Behring, the Pennsylvania-based subsidiary of CSL Limited, already markets such therapies, which are made from donated human plasma. But hemophilia B patients need these infusions for life.
Hemgenix is a single treatment. The therapy uses an engineered virus to deliver to patients’ liver cells a version of the FIX gene that is designed to restore production of the deficient clotting protein. The FDA approval was based on an open-label study involving 57 adult men aged 18 to 75 years with moderate to moderately severe hemophilia B. The primary objective was to measure the change in annual bleeding frequency.
The results showed that seven to 18 months after the infusion, the mean adjusted annual bleeding rate was reduced by 54% compared to baseline. In addition, 51 of 54 patients, or 94%, discontinued the use of prophylactic FIX infusions. But the therapy does not fully restore FIX production to the levels of a typical healthy person. The mean FIX activity of study patients was 39% at six months post-infusion; at 24 months it is 36.7%.
The most common side effects reported in the clinical trial were high liver enzyme levels, headache, infusion-related reactions, and flu-like symptoms. The FDA said patients should be monitored for infusion reactions and elevated liver enzymes, which could be a sign of liver toxicity. During Hemgenix’s clinical development, a case of liver cancer prompted the FDA to pause tests of the gene therapy. An independent study concluded that this Cancer is unlikely to be related to gene therapywhich leads to eliminating clinical detention. The death of one patient in the study was due to cardiogenic shock and sepsis that spread from the urinary tract to the kidneys — both considered unrelated to the gene therapy.
Clinical trial data for 18 months were presented earlier this year at the annual meeting of the European Association of Hemophilia and Related Disorders. The company plans to present updated 24-month follow-up data next month at the American Society of Hematology’s annual meeting.
Like other gene therapies, the one-time treatment comes with a high price. CSL Behring’s list price of $3.5 million for Hemgenix exceeds the range of $2.93 million to $2.96 million in which the Institute for Clinical and Economic Review (ICER), a drug price watchdog group, estimate that the therapy will be cost-effective. When the report was published earlier this month, it used a price of $4 million to value Hemgenix. At that price, ICER said the CSL Behring gene therapy breaks even after 8.5 years — if the treatment lasts that long.
Pricing experts and consultants note that the extremely high costs of gene therapies are pushing pharmaceutical and biotech companies to adopt value-based or outcome-based agreements. These pacts tie therapy recovery to certain goals or outcomes. Bluebird Bio announced such an agreement for Zynteglo, its recently approved gene therapy for the rare blood disorder beta thalassemia. If patients do not achieve and maintain transfusion independence after two years, Bluebird Bio has promised to refund part of the $2.8 million cost of the therapy.
In an emailed statement, CSL Behring said it will also offer value-based agreements to commercial payers, although it did not disclose any details about those pacts. Because hemophilia B is a rare disease, affecting about 6,000 patients in the U.S. and an even smaller number of those requiring FIX therapy, only a small percentage of people will be eligible for Hemgenix, the company said. This means that Hemgenix’s impact on health system budgets will be very small. The company also claims that Hemgenix will save money by reducing the duration of costs associated with managing the bleeding disorder.
“We are confident that this price point will generate significant cost savings for the overall healthcare system and significantly reduce the economic burden of hemophilia B by reducing annual bleeding rates, reducing or eliminating prophylactic therapy, and generating increased FIX rates.” that last for years,” CSL Behring said.
In addition to being a first-in-class gene therapy, Hemgenix is also a best-in-class hemophilia B therapy, William Blair analyst Sammy Corwin said in a research note sent to investors on Wednesday. The firm’s survey of US physicians who treat hemophilia found that a weighted average of 36 percent of adult hemophilia B patients would be good candidates for gene therapy. This was less than the weighted mean of those classified as having severe or moderate disease, but in line with the weighted mean of patients receiving FIX infusions to prevent bleeding episodes. The latter group could be an early adopter of the CSL Behring gene therapy, Corwin said.
CSL Behring acquired Hemgenix two years ago, paying uniQure $450 million upfront. The Dutch company could receive up to $1.6 billion depending on the achievement of milestones.
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