Three years after introducing Hemgenix, the first gene therapy for hemophilia B, CSL Behring has released long-term data proving the treatment’s benefits remain durable after five years.
The five-year data from CSL’s Hope-B trial answer a question patients have been asking for years, Deborah Long, M.D., senior vice president and head of medical affairs, told Fierce Pharma in an interview. While the therapy’s approval in 2022 represented a landmark innovation to replace injectable prophylaxis and bleeding treatments, its staying power remained a question mark until now.
The update, presented at this year’s American Society of Hematology (ASH) annual meeting and simultaneously published in The New England Journal of Medicine, comes from 51 adult male patients five years after receiving a single dose of Hemgenix. CSL assessed the participants’ annual bleeding rate (ABR) and compared it to the baseline ABR calculated for 54 patients during an initial six-month observation period that took place before receiving the gene therapy.
At year five, the mean adjusted ABR for all bleed types diminished approximately 90% from the lead-in rates, from about 4.2 to 0.4. Joint bleeds specifically were reduced by 93% and spontaneous bleeds by 94%, CSL reported. Throughout the entire post-treatment period, the adjusted ABR for all bleeding events was 1.52, translating into a 63% reduction.
Following Hemgenix infusion, 51 (94%) patients no longer required continuous prophylaxis treatment. One participant had an initial response after treatment and had to resume factor IX prophylaxis at about 2.5 years due to a decrease in factor IX activity and concurrent bleeding events. This calculation also includes two participants who did not have an initial treatment response, including one who had a high level of neutralizing antibody against the viral vector carrying Hemgenix and one who received a suboptimal dose because of hypersensitivity reaction.
The study results also allow for more visibility into a year-by-year durability scale proving how the therapy boosts levels of factor IX, a key blood-clotting factor that hemophilia B patients lack. Over the five years, mean factor IX activity levels of participants were sustained at greater than 36% over years one through five post-infusion. More specifically, mean factor IX activity levels stood at 41.5 IU/dL at year one, 36.7 IU/dL at year two, 38.6 IU/dL at year three, 37.4 IU/dL at year four and 36.1 IU/dL at year five.
Two deaths were recorded over the study, which were each ruled non-treatment-related events. One instance of myelodysplastic syndrome was initially suspected to be potentially treatment-related but was determined not to be. Elsewhere, study investigators logged a total of 100 treatment-related adverse events, most of which occurred within the first four months post-infusion. Only five of these events happened between years four and five.
Overall, the five-year results largely matched or improved upon the original Hope-B trial results that won Hemgenix FDA approval in 2022. Next up is an extended study that will track patients for up to 15 years post-treatment, the company said.
“To be able to move to a space where we have the opportunity to offer people living with hemophilia B a single infusion, one-time therapy and transition their lives from this burden of treatment of continuous injections over their whole life span to being independent of those injections is really incredible,” Long said.
With the longer-term data in hand, it’s possible CSL could knock down some of the walls that may prevent eligible patients from exploring the option of gene therapy. Many patients and caregivers within the hemophilia B community hold what Long calls a “very reasonable caution” toward gene therapies, she said.
This caution may stem in part from the relative newness of gene therapies or from a hesitancy to switch up from traditional infusions that, while burdensome, may be working well. Some may prefer to wait and see before jumping on board.
If the last few years were the “wait,” CSL’s head of U.S. Diego Sacristan thinks that now is the time to “see.”
Access and expansion hurdles
The hemophilia B patient community is a tight-knit one, Sacristan explained in the interview. With a network of real-world patients around to reflect on their experience, the “power of the patients themselves” could be significant for driving future adoption, he said.
So far, CSL has racked up more than 75 Hemgenix patients on the commercial market, including more than 50 who are based in the U.S., according to Sacristan. While this level of uptake may be marginal for other drug classes, “we need to think about gene therapy in a completely different way” than for any other therapy, he said.
“It is a pathway that requires work, because the system has a lot of hurdles,” Sacristan noted.
Such hurdles, such as evolving infrastructure, restrictions on eligibility, pricing concerns and other barriers have left CSL as the last one standing in the hemophilia gene therapy space. CSL briefly faced a market rival in Pfizer’s Beqvez, which, like Hemgenix, launched at an eye-popping list price of $3.5 million per one-time dose. But, unlike Hemgenix, “limited interest toward hemophilia gene therapies” pushed Pfizer into discontinuing its offering after less than a year of commercialization.
It’s important to note that experts such as the World Federation of Hemophilia’s VP of medical, Glenn Pierce, M.D., Ph.D., rejected Pfizer’s notion of a lack of patient and physician interest, noting instead that Beqvez’s less competitive profile in comparison to Hemgenix “perhaps account[ed] for its market withdrawal,” Pierce countered in a June paper.
While Pfizer struggled to even get its foot in the door and didn’t end up dosing a single patient on the commercial market, the rocky road to success for hemophilia gene therapies has proven to not be hemophilia B-specific. BioMarin recently moved to effectively throw in the towel for its hemophilia A gene therapy Roctavian, resigning to remove the asset from its portfolio through a divesture.
That’s not to say that CSL has had smooth sailing. Despite its established history in blood therapies, the company had a tough time “slowly but steadily navigating the “complexities of the U.S. healthcare system,” CEO Paul McKenzie said on a call last February.
Still, CSL has repeatedly reiterated its commitment to Hemgenix and the patient population it serves, amassing a “big recognition” from patients and the wider scientific community that have praises its continued perseverance and efforts, Sacristan said.
Sacristan estimates the total eligible patient population in the U.S. to consist of 800 patients. To reach those 800, the plan is to spread the five-year data to prospective patients through a “very detailed and very broad” communication push with CSL’s medical team and its patient support teams, Sacristan said. The company will also celebrate its 50-patient mark in the U.S. in the hopes of building confidence through its real-world evidence and consistent clinical trial data.
Hemgenix on the commercial market is something of a “one-at-a-time type of work,” Sacristan mused. “We have the resources and we have the commitment to support these patients one at a time, and we see this being a continuous process of dosing patients over many, many years.”
Sixty-four centers have so far been trained on Hemgenix administration in the U.S. Meanwhile, the company is still looking to expand its global reach with a “phased approach” and has so far notched approvals in Canada, the U.K., Switzerland, Australia, Saudi Arabia, Taiwan, South Korea, Singapore and Hong Kong, plus a conditional marketing authorization from the European Commission.
“We are more excited than ever,” Sacristan continued, emphasizing that “more than 50 patients in the U.S., more than five years of monitoring for the clinical trial,” marked a “pivotal moment” for the company.
Melbourne, Australia-based CSL reported 189% Hemgenix sales growth to $92 million during its 2025 financial year, which ended on June 30 on the company’s fiscal calendar.