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US Approves Gene Therapy Treatment For Hemophilia

Pfizer's Beqvez, which is given as a single intravenous infusion, was shown in a clinical trial of 45 people to be better at preventing bleeding among adults with moderate to severe hemophilia B, compared to regular infusions of a protein that promotes clotting SPENCER PLATT

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Pharmaceutical giant Pfizer has received US approval for a gene therapy against a form of hemophilia, a rare and inherited blood clotting disorder, the company said Friday.

Beqvez, which is given as a single intravenous infusion, was shown in a clinical trial of 45 people to be better at preventing bleeding among adults with moderate to severe hemophilia B compared to regular infusions of a protein that promotes clotting, called protein factor IX (FIX).

The current standard of care is cumbersome, requiring infusions up to several times per week.

"Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues," said Adam Cuker, director of the University of Pennsylvania's Comprehensive Hemophilia and Thrombosis Program, in a Pfizer statement.

"A one-time treatment with BEQVEZ has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term."

The therapy was generally well tolerated but a common side effect was elevated liver enzymes, a sign of liver inflammation that wasn't accompanied by outward symptoms. Still, patients are advised to avoid alcohol for up to a year following their treatment, to prevent liver damage.

Patients will be followed up to gather more data for up to 15 years.

Pfizer's genetic therapy targets hemophilia B, the second most common form of the condition, which primarily affects males. More than 38,000 people worldwide live with hemophilia B, according to the World Federation of Hemophilia.

It works by infecting the body with a virus, modified to be harmless, which delivers a functional copy of the factor IX gene to liver cells, instructing them to produce the protein that promotes clotting that the patient otherwise lacks.

It received approval by Canada in January and is awaiting review by the European Medicines Agency.

It comes with a hefty list price of $3.5 million. But a Pfizer spokesperson said that the cost for people with insurance would likely be less. By comparison, the annual cost of the current treatment "may be more than $600,000 and as high as $1.1 million," whereas Beqvez is a one-time dose.

The Barron's news department was not involved in the creation of the content above. This article was produced by AFP. For more information go to AFP.Com.© Agence France-Presse

FDA Approves Pfizer's Beqvez For The Treatment Of Adults With Moderate To Severe Hemophilia B

Beqvez, a one-time gene therapy, offers hope to patients with moderate to severe hemophilia B who use regular factor IX prophylaxis, suffer severe hemorrhages, or recurrent serious bleeding.

Image Credit: Adobe Stock Images/angellodeco

Pfizer announced that the FDA has approved Beqvez (fidanacogene elaparvovec-dzkt) as a one-time gene therapy for adults with moderate to severe hemophilia B. The therapy is indicated for patients who currently use factor IX (FIX) prophylaxis therapy, have a history of severe hemorrhage, or experience frequent serious bleeding with no neutralizing antibodies to the adeno-associated virus serotype. In clinical trials, Beqvez was found to help patients to produce their own FIX, lowering the need for regular intravenous (IV) infusions.

The approval was based on promising data from the Phase III open-label, single-arm BENEGENE-2 trial, which evaluated the efficacy and safety of Beqvez in 45 males aged 18 to 65 years with moderately severe to severe hemophilia B. All participants were required to have completed a minimum of six months routine FIX prophylaxis therapy during the lead-in study, also while receiving a single IV infusion of the therapy. Pfizer reported that the primary endpoint of non-inferiority was met, with bleeds no longer present in 60% of patients treated with Beqvez compared to 29% with prophylaxis. While it was well tolerated, a common adverse effect was an increase in transaminases.1

"Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues," said Adam Cuker, MD, MS, director, Penn Comprehensive and Hemophilia Thrombosis Program, in a press release. "A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term."

According to the National Organization for Rare Disorders (NORD), hemophilia B affects one in 25,000 males at birth, with many female carriers not experiencing any symptoms. However, around 10%-25% are expected to develop mild symptoms. Severe symptoms are usually discovered after birth, moderate symptoms around the ages of five or six years, and mild symptoms typically manifesting much later in life.2

"Hemophilia B is caused by a change (variant or mutation) in the F9 gene. The F9 gene is located on the X chromosome and thus is inherited in an X-linked recessive pattern. In about 30% of cases of hemophilia B, the altered gene occurs spontaneously without a previous family history," reports NORD. "The F9 gene contains instructions for creating the factor IX protein. Variants in the F9 gene can lead to deficient levels of functional factor IX protein. The bleeding symptoms associated with hemophilia B occur due to this deficiency."

Hemophilia B is classified as a rare genetic bleeding disorder that prevents normal blood clotting due to deficiencies in FIX that cause longer bleeding periods. Currently, the top treatment is prophylactic infusions of FIX replacement therapy, which is only a temporary solution. According to data Pfizer displayed from the World Federation of Hemophilia, more than 38,000 people live with hemophilia B globally.1

"This milestone is a testament to Pfizer's continued effort to advance the standard of care for people living with hemophilia, with the delivery of a medicine that has the potential to offer both long-term bleed protection and value to the healthcare system because of its one-time administration," said Aamir Malik, chief US commercial officer, EVP, Pfizer, in the press release. "We are leveraging our expertise that comes with more than 40 years of experience in the hemophilia space, and are proactively working with treatment centers, payers, and the hemophilia community to appropriately help ensure the healthcare system is prepared to readily deliver Beqvez to the patients who can benefit from it."

References

1. U.S. FDA Approves Pfizer's BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. Pfizer. April 26, 2024. Accessed April 26, 2024. Https://www.Pfizer.Com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec

2. Hemophilia B. NORD. September 20, 2023. Accessed April 26, 2024. Https://rarediseases.Org/rare-diseases/hemophilia-b/

FDA Approves One-Time Gene Therapy Fidanacogene Elaparvovec For Hemophilia B

The FDA has approved fidanacogene elaparvovec-dzkt (Beqvez; Pfizer), a gene therapy administered in a one-time dose, for certain patients with moderate to severe hemophilia B.

The FDA has approved Pfizer's fidanacogene elaparvovec-dzkt (Beqvez) for the treatment of moderate to severe hemophilia B currently using prophylactic factor IX (FIX) therapy or have current or past life-threatening hemorrhage or serious bleeding episodes, and who do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid, the company announced today.1

Hemophilia is a rare genetic bleeding disorder characterized by abnormal blood clotting due to FIX deficiency, leading patients to bleed for longer and more frequently than others.2 Fidanacogene elaparvovec is a one-time therapy designed to enable those with hemophilia B to produce their own FIX, while the current standard of care entails regular intravenous infusions of FIX multiple times per week or month.1,3

"Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues," Adam Cuker, MD, MS, director of the Penn Comprehensive and Hemophilia Thrombosis Program, said in a statement.1 "A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term."

FDA ApprovedImage credit: chrisdorney - stock.Adobe.Com

Fidanacogene elaparvovec's approval is based on results from the pivotal phase 3, open-label BENEGENE-2 study (NCT03861273), a single-arm study evaluating the therapy's efficacy and safety in 45 adult male participants aged 18 to 65 years.4 The main objective of BENEGENE-2 was to assess the annualized bleeding rate (ABR) for patients treated with a single intravenous dose of fidanacogene elaparvovec compared with standard-of-care prophylactic FIX replacement therapy.1

Participants in the study had moderately severe to severe hemophilia B, which was defined as circulating FIX activity of 2% or less, and all completed a minimum of 6 months of FIX prophylaxis therapy during a lead-in study before receiving fidanacogene elaparvovec.

The study reached its primary end point, which was gene therapy's non-inferiority to standard prophylactic FIX therapy in terms of the ABR of total bleeds following fidanacogene elaparvovec infusion vs FIX prophylaxis. Patients who received a one-time dose of gene therapy had a mean ABR of 2.5 during the efficacy evaluation period from week 12 of the study to data cutoff, which was a median 1.8 years of follow-up. Those receiving standard FIX prophylaxis had an ABR of 4.5 during the 6-month treatment lead-in period at a median 1.2 years of follow-up.

Further, bleeds were eliminated in 60% of those who received fidanacogene elaparvovec vs 29% when receiving prophylaxis. The median ABR was 0 (range, 0-19) with fidanacogene elaparvovec vs 1.3 (range, 0-53.9) with usual prophylaxis.

Patients participating in the trial will be followed for up to 15 years total, including 6 years for the BENEGENE-2 study and 9 years in a phase 3 study (NCT05568719) on the therapy's long-term safety and efficacy.

Overall, fidanacogene elaparvovec was well-tolerated, with an increase in transaminases being the most common adverse reaction with an incidence of 5% or more in the phase 3 and 1/2 studies. Twenty-six out of 60 patients treated at the recommended dose of fidanacogene elaparvovec showed elevated transaminases, and 31 out of 60 patients received corticosteroids. There were no deaths or serious adverse reactions related to fidanacogene elaparvovec or associated with infusion reactions, thrombotic events, or FIX inhibitors.

Pfizer is launching a warranty program based on the durability of patient responses to the one-time treatment, with the goal of maximizing access for eligible patients, giving payers greater certainty, and insuring against the risk of efficacy failure to offer financial protection, according to the news release.

"For people living with hemophilia, disease management can interfere with many aspects of their lives. A one-time infusion of Beqvez may allow eligible patients more time for the things they love," Kim Phelan, chief operating officer at The Coalition for Hemophilia B, said.1 "We are excited to have Beqvez as a promising treatment option for eligible people living with hemophilia B. We look forward to learning more and celebrating with the community and with Pfizer at our annual conference that is currently taking place."

References

1. U.S. FDA approves Pfizer's Beqvez (fidanacogene elaparvovec-dzkt), a one-time gene therapy for adults with hemophilia B. News release. Pfizer. April 26, 2024. Accessed April 26, 2024. Https://www.Businesswire.Com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B

2. Hemophilia B. National Organization for Rare Disorders. Updated September 20, 2023. Accessed April 26, 2024. Https://rarediseases.Org/rare-diseases/hemophilia-b/

3. Hart DP, Matino D, Astermark J, et al. International consensus recommendations on the management of people with haemophilia B. Ther Adv Hematol. Published online April 22, 2022. Doi:10.1177/20406207221085202

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