Beqvez (fidanacogene elaparvovec-dzkt) for hemophilia

Last updated July 30, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Beqvez for hemophilia?

Beqvez (fidanacogene elaparvovec-dzkt), previously known as SPK-9001 or PF-06838435, is a gene therapy approved in the U.S. to treat certain adults with moderate to severe hemophilia B. It’s designed to prevent bleeding episodes in patients with this disease type, which accounts for about 15% to 20% of all hemophilia cases in the U.S.

The therapy also is approved in Canada and Europe to treat severe and moderately severe hemophilia B in adults. In Europe, the therapy will be available under the brand name Durveqtix.

The one-time therapy, given via an intravenous or into-the-vein infusion, is marketed by Pfizer. Roche subsidiary Spark Therapeutics had been codeveloping it, but transferred full responsibility to Pfizer in 2018.

Therapy snapshot

How does Beqvez work?

Hemophilia B is caused by mutations in the F9 gene, which carries instructions for making factor IX (FIX), a protein involved in the formation of blood clots. Mutations in the gene cause the protein to be faulty or missing completely, and blood clotting to be impaired, leading to the recurrent and difficult-to-control bleeding episodes that characterize the disease.

Beqvez is a gene therapy designed to deliver a highly functional version of F9 to liver cells, where blood clotting factors are mostly produced. The version of F9 that Beqvez delivers is called Padua, a naturally occurring form of the gene containing a single mutation that encodes a version of FIX that has 5-10 times greater clotting activity than the regular form of the protein.

The gene is packaged inside a specialized adeno-associated virus (AAV) carrier. It contains a recombinant, or lab-made, outer shell, known as AAVRh74var capsid, which helps it be taken up by liver cells when delivered via an intravenous infusion. The AAVRh74var capsid is derived from a naturally occurring AAV serotype (Rh74) that is not known to cause disease in humans.

Once the gene therapy components are taken up, target cells can use the F9 gene to continuously produce their own version of FIX, thereby preventing bleeding episodes.

Who can take Beqvez?

The U.S. Food and Drug Administration (FDA) approved Beqvez in April 2024 for the treatment of adults with moderate to severe hemophilia B who currently use preventive (prophylactic) FIX replacement therapy, have a current or past history of life-threatening bleeds, or have repeated, serious spontaneous bleeding episodes, and who do not have neutralizing antibodies against the AAVRh74var capsid.

Beqvez was also approved by Health Canada in January 2024, followed by the European Union in July 2024, for adults with moderately severe to severe hemophilia B.

Who should not take Beqvez?

There are no contraindications for Beqvez’s use, but hemophilia B patients must undergo certain tests to make sure they are eligible to receive treatment.

Beqvez should not be used in patients in whom blood tests come back positive for:

• neutralizing antibodies against the AAVRh74var capsid, as detected by an FDA-approved companion diagnostic test
• neutralizing antibodies (inhibitors) against FIX, or a prior history of such inhibitors
• signs of active HIV-1 or HIV-2 infection.

Liver health assessments also will be performed before treatment, and patients with certain liver conditions may not be eligible for Beqvez or will require special consultation with a hepatologist before receiving treatment. Hepatologists are doctors who diagnose and treat diseases associated with the liver and other organs of the digestive system.

Beqvez also should not be used by patients with a history of exaggerated immune responses (hypersensitivity) to FIX replacement therapies. The therapy also is not intended to be used in women.

How is Beqvez administered?

Beqvez is given as a single intravenous infusion, lasting about an hour, and administered at a hospital or clinic. It must be done under the supervision of a physician experienced in the treatment of hemophilia. The therapy’s recommended dose is 5×10¹¹ vector genomes per kilogram of body weight (vg/kg), with certain adjustments in heavier patients who have a body mass index (BMI) greater than 30. BMI is a person’s ratio of weight to height, and is used as a measure of body fat.

The medication comes as a liquid suspension in vials at a concentration of approximately 1×10¹³ vg/mL that will be diluted in sterile saline and human serum albumin for infusion. A doctor will determine how many vials are necessary to meet the weight-based dose requirements. Beqvez should be administered within a period of 24 hours after being prepared.

After the infusion, Beqvez can be transmitted from a patient to others through bodily excretions and secretions, such as urine, feces, saliva, mucus, or semen. Patients should be instructed about proper hygiene methods to avoid such transmission, and these precautions should be taken for six months after the infusion, especially if a patient is in close contact with any person who is pregnant or immunodeficient.

After Beqvez is administered, lab tests for liver function and FIX activity are recommended once or twice weekly for the first four months. The frequency of these tests can gradually be reduced over the first six years following treatment. Following the sixth year, testing should be done annually. Certain changes in liver enzymes or FIX activity may warrant treatment with corticosteroids.

Beqvez in clinical trials

The safety and pharmacological properties of Beqvez were initially investigated in an open-label Phase 1/2a study (NCT02484092) involving 15 men with hemophilia B. The men were experiencing at least four bleeds per year on average, and required on-demand or preventive treatment with FIX products.

All received a single infusion of the gene therapy, given at a dose of 0.5 trillion vg/kg, but the last five patients were treated with an improved version. The participants then were followed for up to a year. A long-term observational study (NCT03307980) is continuing to follow these individuals, as well as a subgroup of patients who didn’t participate in the earlier trial and received a higher dose of the therapy.

Results announced in 2018, with a follow-up time of 5-121 weeks post-treatment, showed average bleeding rates decreased by 98% within four weeks. The participants went from having an average of 8.9 bleeds per year before receiving the gene therapy to 0.2 bleeding episodes per year after treatment.

Further, the participants also stopped taking their preventive FIX infusions, with the annualized rate of infusions used to control or prevent bleeds dropping by 99%.

BENEGENE-2 trial

After the promising results from the Phase 1/2a study, a Phase 3 clinical trial called BENEGENE-2 (NCT03861273) was launched to evaluate the gene therapy in a larger population of hemophilia B patients. Pfizer’s regulatory applications seeking Beqvez’s approval are based on data from this trial.

The ongoing study enrolled 45 men, ages 18-65, with moderately severe to severe hemophilia B, who had FIX activity levels of 2% or lower than normal. These participants first took part in a lead-in study (NCT03587116) in which they were monitored for at least six months while on standard FIX replacement therapy. The men then received a single intravenous infusion of Beqvez at its now recommended dose.

According to these results, the mean annualized bleeding rate dropped from 4.5 bleeds per year in the lead-in study to 2.5 bleeds per year during the Beqvez efficacy period — the period spanning between three months after the infusion and the data cut-off, with a median follow-up of 1.8 years.

The median annualized bleeding rate similarly declined from 1.3 bleeds per year in the lead-in study to zero after Beqvez was administered. More than half of the participants (60%) did not experience any bleeds after receiving the gene therapy, while fewer than one-third (29%) did while being on replacement therapy during the lead-in study. Six people (13%) resumed FIX replacement therapy from 0.4 to 1.7 years after receiving Beqvez.

Patients now will be evaluated for up to a total of 15 years to assess the gene therapy’s long-term safety and efficacy outcomes, including six years in BENEGENE-2 and an additional nine years as part of a separate Phase 3 extension study (NCT05568719).

Common side effects of Beqvez

The most common side effect associated with Beqvez in clinical trials was an increase in the levels of certain liver enzymes.

Liver toxicity

Intravenous infusions of a liver-directed viral carrier, such as the one used in Beqvez, can lead to elevations in the levels of certain liver enzymes. It also could potentially reduce the treatment’s therapeutic efficacy.

Liver enzyme levels should be monitored once or twice weekly for at least four months after Beqvez treatment. Should elevations in liver enzymes and/or decreases in FIX activity occur, corticosteroid treatment should be started as needed, while monitoring patients for adverse side effects and adjusting vaccination schedules as necessary. In the first year after receiving Beqvez, patients also should limit their alcohol consumption, because alcohol can impact liver function.

It also is possible that certain medications that compromise liver function may reduce Beqvez’s efficacy or increase the risk of serious liver-related events. Physicians should review all medications that patients are taking to determine if modifications need to be made before Beqvez is administered.

Infusion reactions

Infusion-related reactions, including hypersensitivity or anaphylaxis — a life-threatening reaction — may occur after treatment with Beqvez, with symptoms including low blood pressure, fever, palpitations, nausea, vomiting, chills, or headache. Patients should be closely monitored for signs of a reaction during the infusion and for at least three hours afterward. If a reaction does occur, the infusion may be slowed or stopped and restarted at a slower rate after the issue has resolved. Treatment with antihistamines, corticosteroids, or other medications may be required.

Cancer

The integration of a viral carrier into human liver cells carries a theoretical risk of liver cancer. Patients with other risk factors, such as hepatitis, fatty liver disease, alcohol consumption, or advanced age should be monitored annually for the first five years after dosing.

FIX levels and development of inhibitors

FIX levels should be regularly measured and patients should be monitored for signs of FIX inhibitor development after Beqvez administration. A test for inhibitors should be performed if bleeding is not controlled or FIX activity levels decrease. In some cases, a drop in FIX levels may require treatment with corticosteroids.

Use in pregnancy and breastfeeding

There are no data on the use of Beqvez during pregnancy or lactation in humans or in animals. The gene therapy is not intended to be administered in women. Because the therapy can potentially be transmitted through semen, it’s recommended that men receiving Beqvez abstain from donating sperm and use an effective form of contraception for up to six months after receiving the gene therapy.

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 other 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.