Pfizer’s first FDA-approved gene therapy is the second such treatment for the inherited bleeding disorder hemophilia B, introducing some competition to a therapeutic area that now has two of the most expensive medicines in the world.
The FDA approval announced Friday covers the treatment of adults with moderate-to-severe hemophilia B. Known in development as fidanacogene elaparvovec, the Pfizer therapy will be marketed under the brand name Beqvez. The company expects this therapy will become available to patients later in the current quarter.
Hemophilias stem from genetic mutations that lead to abnormally low levels of clotting proteins. These disorders mainly affect males and make patients susceptible to bleeding events that can be life-threatening. Standard treatment is prevention of bleeding episodes through frequent infusions of clotting proteins that are either engineered in a lab or sourced from healthy donors. Hemophilia B affects the clotting protein factor IX (FIX). It’s rarer than hemophilia A, which is the most common form of the disorder. The world Federation of Hemophilia estimates that more than 38,000 people in the world have hemophilia B.
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Beqvez uses an adeno-associated virus (AAV) to deliver a functional copy of the FIX gene to a patient’s liver cells, enabling them to produce FIX protein. It’s a one-time treatment that potentially eliminates the need for frequent FIX infusions. The FDA approval covers the treatment of patients who are currently receiving FIX therapy or have a history of life-threatening or serious bleeding events. Before receiving the therapy, patients must first be tested to make sure they do not have any antibodies against the AAV used to deliver the gene. Those antibodies can be identified with an FDA-approved companion diagnostic.
The FDA decision for Beqvez is based on the results of an open-label Phase 3 clinical trial that evaluated the gene therapy in adult males with moderate-to-severe hemophilia B. First, participants received standard of care FIX therapy for six months in a lead-in study that served as the control group for the clinical trial. Patients then received Beqvez, which is administered as an intravenous infusion according to body weight.
The clinical trial’s main goal was to measure annualized bleeding rates. Results showed that bleeds were eliminated in 60% of patients in the Beqvez arm compared to 29% in the standard of care arm. The median annual bleeding rate in the treatment arm was 0 compared to 1.3 for the standard of care. The therapy was well tolerated by patients. The most common adverse reaction was higher levels of liver enzymes, which can be a sign of drug toxicity. The liver enzymes were managed with corticosteroids. Beqvez’s label does not carry a black box warning, but elevated liver enzymes are included in the “Warnings and Precautions” section of the document. The label advises clinicians to monitor a patient’s liver enzyme and FIX levels once or twice weekly for at least four months after administering the gene therapy.
Pfizer set a $3.5 million price for Beqvez, which is on par with Hemgenix, a hemophilia B gene therapy developed by CSL Behring and uniQure. That product’s 2022 approval made it part of a portfolio of CSL hemophilia products. Hemgenix has yet to become a blockbuster seller. Sales of the gene therapy are not big enough for CSL to break out individually, but company financial reports show its top hemophilia product continues to be Idelvion, a FIX replacement therapy for hemophilia B. Idelvion’s sales have been growing despite the commercial availability of a gene therapy that could obviate the need for FIX replacement. Meanwhile, BioMarin Pharmaceutical has had difficulty gaining market traction for Roctavian, the first FDA-approved gene therapy for hemophilia A. The market performance of both Hemgenix and Roctavian suggests Pfizer could face similar challenges persuading patients to choose its new gene therapy.
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When Hemgenix was approved in 2022, its price tag made it the most expensive medicine in the world (a status since surpassed by Kyowa Kirin’s Lenmeldy, a $4.5 million gene therapy approved in January for treating a rare enzyme deficiency). CSL said at the time that the hefty price reflects the value of reducing the economic burden of frequent FIX infusions and caring for bleeding episodes over the lifetime of a patient. To offset the financial risk of covering the therapy, CSL offers insurers a value-based agreement that ties reimbursement to a patient’s achievement of certain goals or outcomes.
Value-based programs are becoming common for pricey gene therapies, and Pfizer’s version is a warranty that guards against the risk that Beqvez does not work. In an email, Pfizer said this warranty is based on the durability of the therapy’s effect and will provide payers with greater certainty while also maximizing access to the therapy for eligible patients. For commercially insured patients, their coverage under the warranty will continue even if they change insurance plans after receiving the gene therapy.
“This was informed by pre-approval information exchange discussions we have had with payers to understand how we can best ensure access,” Pfizer said. “The program speaks to the confidence that we have in both our medicine’s ability to deliver for patients as well as value that it can offer the healthcare system.”
Pfizer licensed Beqvez from Spark Therapeutics in 2014. That company, now a subsidiary of Roche, is eligible for milestone payments and royalties from Pfizer’s sales of Beqvez. The gene therapy won its first regulatory approval in Canada in January. Pfizer has more in its hemophilia pipeline. Marstacimab, an antibody drug developed to treat both hemophilia A and B, is under regulatory review in the U.S. and Europe; an FDA decision is expected in the fourth quarter of this year. Full Phase 3 results for marstacimab were presented last December during the annual meeting of the American Society of Hematology. In gene therapy, Pfizer’s pipeline includes giroctocogene fitelparvovec for hemophilia A and fordadistrogene movaparvovec for Duchenne muscular dystrophy.
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