Pfizer’s FDA-approved gene therapy is the second such treatment for the congenital bleeding disorder hemophilia B, bringing some competition to a therapeutic area that now boasts two of the most expensive drugs in the world.
The FDA approval announced Friday covers the treatment of adults with moderate to severe hemophilia B. The Pfizer therapy, known in development as Fidanacogene Elaparvovec, will be marketed under the brand name Beqvez. The company expects this therapy to be available to patients during the current quarter.
Hemophilia is caused by genetic mutations that lead to abnormally low levels of clotting proteins. These diseases primarily affect men and make patients susceptible to bleeding, which can be life-threatening. The standard treatment is to prevent bleeding episodes with frequent infusions of clotting proteins, either made in the laboratory or obtained from healthy donors. Hemophilia B affects the clotting protein factor IX (FIX). It is rarer than hemophilia A, the most common form of the disease. The World Federation of Hemophilia estimates that more than 38,000 people worldwide suffer from hemophilia B.
Beqvez uses an adeno-associated virus (AAV) to introduce a functional copy of the FIX gene into a patient’s liver cells, enabling them to produce FIX protein. It is a one-time treatment that may eliminate the need for frequent FIX infusions. The FDA approval covers the treatment of patients who are currently receiving FIX therapy or who have a history of life-threatening or serious bleeding. Before therapy, patients must first be tested to ensure they do not have antibodies to the AAV used to transmit the gene. These antibodies can be identified using an FDA-approved companion diagnostic.
The FDA’s decision for Beqvez is based on the results of an open-label Phase 3 clinical trial evaluating the gene therapy in adult men with moderate to severe hemophilia B. Participants initially received standard therapy for six months with FIX lead-in study serving as a control group for the clinical trial. The patients then received Beqvez, which is administered as an intravenous infusion depending on body weight.
The main objective of the clinical trial was to measure the annual bleeding rate. Results showed that bleeding was eliminated in 60% of patients in the Beqvez arm, compared to 29% in the standard treatment arm. The mean annual bleeding rate in the treatment arm was 0 compared to 1.3 in the standard treatment group. The therapy was well tolerated by the patients. The most common side effect was an increase in liver enzyme levels, which may be a sign of drug toxicity. Liver enzymes were controlled with corticosteroids. There is no black box warning on Beqvez’s label, but elevated liver enzymes are listed in the “Warnings and Precautions” section of the document. The label recommends that doctors monitor a patient’s liver enzyme and FIX levels once or twice weekly for at least four months after receiving gene therapy.
Pfizer set a price of $3.5 million for Beqvez, which is comparable to Hemgenix, a hemophilia B gene therapy developed by CSL Behring and uniQure. The approval of this product in 2022 made it part of a portfolio of CSL hemophilia products. Hemgenix has not yet become a blockbuster seller. Gene therapy sales aren’t big enough to break CSL individually, but the company’s financial reports show that the leading hemophilia product remains Idelvion, a FIX replacement therapy for hemophilia B. Idelvion’s sales are despite the commercial availability of a gene increased therapy that could eliminate the need for FIX replacement. Meanwhile, BioMarin Pharmaceutical struggled to break into the market with Roctavian, the first FDA-approved gene therapy for hemophilia A. The market performance of Hemgenix and Roctavian suggests that Pfizer could face similar challenges in convincing patients to choose its new gene therapy.
When Hemgenix was approved in 2022, its price made it the world’s most expensive drug (a status now surpassed by Kyowa Kirin’s Lenmeldy, a $4.5 million gene therapy launched in January to treat a rare enzyme deficiency was approved). CSL said at the time that the high price reflected the value of reducing the economic burden of frequent FIX infusions and management of bleeding episodes throughout a patient’s lifespan. To offset the financial risk of therapy coverage, CSL offers insurers a value-based arrangement that ties reimbursement to the patient’s achievement of specific goals or outcomes.
Value-based programs are increasingly being used for costly gene therapies, and Pfizer’s version is a guarantee that protects against the risk that Beqvez doesn’t work. In an email, Pfizer said this guarantee is based on the durability of therapy effects and provides greater certainty to payers while maximizing access to therapy for eligible patients. For commercially insured patients, warranty coverage will continue even if they change their insurance plan after receiving gene therapy.
“This arose from pre-approval information sharing discussions we have had with payers to understand how we can best ensure access,” Pfizer said. “The program demonstrates the confidence we have in both the performance of our medicine for patients and the value it can provide to the healthcare system.”
Pfizer licensed Beqvez from Spark Therapeutics in 2014. That company, now a subsidiary of Roche, is entitled to milestone payments and royalties from Pfizer’s sales of Beqvez. The gene therapy received its first regulatory approval in Canada in January. Pfizer has more in its hemophilia pipeline. Marstacimab, an antibody drug developed to treat hemophilia A and B, is currently undergoing regulatory review in the United States and Europe; A decision from the FDA is expected in the fourth quarter of this year. Complete Phase 3 results for marstacimab were presented last December during the annual meeting of the American Society of Hematology. In the area of gene therapy, Pfizer’s pipeline includes the giroctocogene fitelparvovec for hemophilia A and the fordadistrogen movaparvovec for Duchenne muscular dystrophy.
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