Abstracts - 2022 - Haemophilia
What's Next After Pfizer's Gene Therapy For Hemophilia B Is Halted?
Gene therapy has long been touted as a revolutionary hope for people with hemophilia B, promising a one-time treatment to drastically reduce — or even eliminate — the need for frequent infusions. Yet that hope has hit another roadblock.
Pfizer announced last week that it's halting development of Beqvez (fidanacogene elaparvovec-dzkt), its gene therapy for hemophilia B that had been approved by the U.S. Food and Drug Administration. Coming after Pfizer discontinued its involvement with a hemophilia A gene therapy in development, this decision has left the bleeding disorders community grappling with uncertainty about the future of gene therapy and access to cutting-edge treatments.
As someone with mild hemophilia B, I've watched gene therapy's rise with intrigue but never with the expectation that it would apply to me. These advancements, I felt, weren't designed for people like me — women with hemophilia or those with mild cases. Clinical trials and treatment guidelines have overwhelmingly targeted men with severe hemophilia, sidelining women and those with less severe forms.
This gap underscores a persistent flaw in bleeding disorder research: a lack of inclusivity that leaves entire groups out of the promise of transformative care.
What stunned me most about Beqvez's cancellation is that no patients have received it outside clinical trials. Demand seems to have fizzled among patients and doctors alike, perhaps overshadowed by newer options like Pfizer's own Hympavzi (marstacimab-hncq) or perhaps because of price ($3.5 million a dose).
Described on the once-weekly treatment's website as "the first and only subcutaneous prophylactic treatment that comes in a fixed-dose, prefilled pen," Hympavzi redefines convenience for hemophilia A and B management. No more vein hunting or infusion hassles — just a quick jab and you're done. For many, that's a genuine game changer, offering a less invasive way to live with this condition.
What Pfizer's move means for the hemophilia B communityFor those who tracked Beqvez's journey or joined its trials, Pfizer's exit stings. Gene therapy symbolizes a bold leap in hemophilia care, but its real-world reach remains elusive. With Beqvez off the table, patients face fewer choices, and the broader field might see innovation stall as companies reassess risks and rewards.
Still, it's not all gloom. CSL Behring's gene therapy treatment Hemgenix (etranacogene dezaparvovec) remains on the market, delivering encouraging results in sustaining factor IX levels from clinical trials.
But challenges persist — cost chief among them. Priced at roughly $3.5 million per dose, as Beqvez was, Hemgenix is out of reach for many, despite insurance and assistance programs aiming to bridge the gap. Eligibility and long-term outcomes also spark debate, leaving patients and providers weighing benefits against unknowns.
Looking ahead, hope endures. Beyond gene therapy, alternatives such as Hympavzi and other rebalancing agents — treatments that tweak anticoagulant pathways to restore clotting balance without replacing factor IX — are gaining traction. These innovations could broaden the toolkit for managing hemophilia.
Yet for them to succeed, the community must demand more than just new options. We need treatments that embrace everyone — women and anyone with mild or moderate cases — not just the narrow slice of patients historically prioritized.
Pfizer's step back from Beqvez isn't the end of the story. It's a pivot point, a chance to rethink how we approach hemophilia care. The future hinges on pushing boundaries, yes, but also on ensuring no one's left behind when breakthroughs arrive.
Note: Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Hemophilia News Today or its parent company, Bionews, and are intended to spark discussion about issues pertaining to hemophilia.
After 4 Years, Hemophilia B Bleeding Rates Remain Low With Hemgenix
Four years after treatment with the gene therapy Hemgenix (etranacogene dezaparvovec), most people with hemophilia B aren't taking preventive therapies and annual bleeding rates remain substantially reduced, new data from the Phase 3 HOPE-B trial shows.
CSL Behring, which markets Hemgenix, presented the results at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) this month in Milan.
"These data continue to instill confidence in the clinical benefits of Hemgenix, highlighting the remarkable impact of this one-time treatment to reduce the frequency of bleeds in people with hemophilia B and improve quality of life by alleviating the burden of ongoing factor IX prophylactic treatment," Andres Brainsky, vice president of research and development for hematology at CSL, said in a company press release.
Hemophilia B is caused by mutations in the gene that provides instructions for making the clotting protein factor IX (FIX). The absence of FIX, or its dysfunctioon leaves patients vulnerable to unusually frequent and prolonged bleeding episodes. Standard preventive, or prophylactic, treatment for hemophilia B consists of replacement therapies, which must be administered regularly to provide patients with a functional version of FIX and reduce the risk of bleeds.
Testing HemgenixHemgenix delivers a working version of the gene that encodes FIX to cells in the liver, where most clotting factors are made. The goal is to restore the body's ability to produce FIX on its own, reducing the risk of bleeds while decreasing or potentially eliminating the need for regular replacement therapy.
Hemgenix was approved in the U.S. In late 2022 for adults with hemophilia B who are on prophylaxis, or have or have had life-threatening bleeding or repeated, serious spontaneous bleeding episodes. The gene therapy has also been approved in the European Union, Australia, Canada, Switzerland, and the U.K.
These approvals were based mainly on findings from the Phase 3 HOPE-B trial (NCT03569891) wherein 54 men with severe or moderately severe hemophilia B were given a single infusion into a vein. Before receiving the gene therapy, all the men were treated with standard prophylaxis for at at least six months to establish a baseline for comparison.
Before treatment, all the men had FIX activity lower than 2% of normal and had more than four bleeds per year.
Top-line results from the study, which covered about 1.5 years of follow-up, showed Hemgenix safely increased FIX activity and reduced bleeding rates. These effects were sustained into two and three years of follow-up. The new data cover four years for 51 patients.
"CSL is committed to continuing to provide ongoing data analyses of Hemgenix, ensuring that healthcare providers and patients have the necessary information to make informed decisions about treatment options," Brainsky said.
After four years of Hemgenix treatmentAt four years post-treatment, the mean FIX activity was at 37.4%. For context, clotting factor activity levels between 5% and 40% are generally considered to be in the mild hemophilia range, while 50% or higher are considered to be within the normal range for people who don't have hemophilia. The vast majority (94%) of patients treated with Hemgenix have remained off prophylactic replacement therapy for four years after treatment.
Consistent with the sustained increase in FIX activity, bleeding rates have remained low. As of year four, the mean adjusted annualized bleeding rate was 0.4 bleeds per year, which corresponds to a 90% decrease over before treatment rates. Joint bleeds were also lower, from a mean of 2.34 per year during prophylaxis to less than 0.1 per year in the fourth year after Hemgenix treatment.
"The four-year data from the HOPE-B study showed that a one-time infusion of Hemgenix (etranacogene dezaparvovec-drlb) continues to offer long-term durability, safety, and greater bleed protection versus prophylactic treatment in people living with hemophilia B," said Steven Pipe, MD, a professor at the University of Michigan who presented the four-year data from HOPE-B, in an email to Hemophilia News Today. "Importantly, no patients returned to continuous prophylaxis treatment between years three and four after infusion, and 94% remained free of continuous prophylactic treatment four years after treatment with Hemgenix."
No serious safety issues related to Hemgenix have been reported in the trial. Almost all side effects related to the therapy occurred within the first few months after treatment. The most common side effects reported were elevations in liver enzymes.
The Most Expensive Drug In The World Has A $3.5 Million Price Tag. 2 Potential Patients Share Their Hopes And Fears For The One-time Treatment.
Bryen Lackey enjoyed bowling, until his blood disorder got in the way.
Lackey is learning to live with a severe case of hemophilia B, a rare genetic condition that keeps blood from clotting properly. That disease required him to have surgery on his right elbow, one of his problematic joints, which has kept the 18-year-old out of his bowling league.
As Lackey prepares to start college next spring, he said he's excited about the potential of a newly approved treatment that could make his life less centered on hemophilia. On November 22, the Food and Drug Administration approved Hemgenix, the first gene therapy to treat hemophilia B. Hematologists hope the one-time treatment could end the weekly infusions that patients like Lackey receive to prevent bleeds.
While the treatment breaks ground as the first approved gene therapy for hemophilia, its price is also unprecedented. The drug's seller, the Australian pharma company CSL Behring, set a list price of $3.5 million for a single treatment, making it the world's most expensive drug — and it remains unclear whether insurance companies will pay for it.
In interviews with Insider, patients shared mixed reactions to that price. Lackey, for instance, estimates his insurance spends $900,000 to $1 million a year on his treatments. That means the gene therapy's price may not be obscene in the long run if its effects last years.
"It seems a little steep," Lackey told Insider, "but compared to what we pay, it doesn't seem too terrible."
A 'good bet' or unfair? Patients and experts are split on $3.5 million price Fajrul Islam/Getty ImagesCSL's new drug is the latest in a series of new gene therapies, which are medicines that modify a patient's DNA to fix the genetic mutation that causes their disease. These treatments can be dramatically effective, with a single infusion leading to transformative benefits.
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But a critical unknown in judging CSL's $3.5 million price is the durability of the treatment. It's unclear how long the treatment will last, as the effects of other gene therapies wane over time. A clinical study of 54 hemophilia B patients showed the one-time treatment reduced bleeds by 64% through 18 months, and 98% of treated patients stopped needing regular preventive infusions.
Leonard Valentino, the CEO of the nonprofit National Hemophilia Foundation, called the price a "good bet," as he expects the therapy to last six to 10 years or even longer, based on clinical data in humans and dogs. The typical cost of regular preventive treatments is $300,000 to $600,000 a year for a patient with severe hemophilia B, he said, which means the gene therapy would be cost effective if it kept patients off of those treatments for many years.
Additionally, the number of patients who are eligible for Hemgenix will be small, meaning the drug's impact on US healthcare costs will be limited. Valentino estimated that 700 to 1,000 adults with hemophilia B in the US might be interested and eligible to receive this gene therapy.
Jerry McMillan Jr., 47, of New York. McMillan has a severe case of hemophilia B. Jerry McMillan Jr.But not all patients think the $3.5 million price is justified. Jerry McMillan Jr., a 47-year-old who has severe hemophilia B, told Insider he believed it's "not a fair price at all" and worried that some insurers might not cover the treatment. He's interested in receiving the gene therapy but said he's worried his Medicare insurance might not cover the cost for him or others. The federal agency hasn't announced yet whether it will cover the cost.
Hemophilia has loomed large through McMillan's life. As a child he went to the emergency room 20 to 24 times a month, and he recently had surgery to replace his left ankle. He's preparing for knee-replacement surgery in January — both operations stemming from the cumulative damage of bleeds throughout his life, he said. He hopes gene therapy could prevent future damage — if he can access and afford it.
"There's going to be a lot of poor people who can't afford this," McMillan said.
Robert Lojewski, a senior vice president and general manager at CSL, told Insider the company would offer co-pay support for people with commercial insurance if insurance companies didn't cover the whole cost of treatment.
Hemgenix is the latest in a string of multimillion-dollar gene-therapy drugsThe Swiss pharma giant Novartis came out with what was then the world's most expensive drug in 2019, when it priced a gene therapy for spinal muscular atrophy at $2.1 million. That record has been passed three times in just the past few months, with Bluebird Bio respectively pricing two gene therapies at $2.8 million and $3 million, before CSL's $3.5 million price.
Lojewski said the $3.5 million price wasn't guided by other gene-therapy prices. Instead, he said that the drug's price came from its value to patients and society and that it could save money for the American healthcare system compared with the lifetime cost of today's hemophilia treatments. The company also plans to offer commercial health insurers a refund on an undisclosed percentage of the cost if the treatment's effect isn't durable, he added.
"From a payer's perspective, whether it's commercial or government, there's savings realized, and the savings are meaningful," Lojewski said.
Benjamin Rome, a health-policy researcher at Brigham and Women's Hospital and Harvard Medical School, told Insider the US healthcare system needed sweeping reform to pay for these one-time treatments. The current system is designed around daily pills taken for chronic conditions, not complex one-time treatments that could be curative, he added.
"A one-time fee is not the best solution," Rome said, "but we don't have a healthcare system that can think about any other ways to do this."
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