Comparable to the world's most expensive drug of $3.5 million, Pfizer hemophilia B gene therapy Phase 3 clinical data is positive

Recently, Pfizer announced that its gene therapy for severe hemophilia type B Fidanacogene Elaparvovec has achieved excellent results in a Phase 3 clinical trial, reaching the primary clinical endpoint, and the number of annual bleeding times in patients receiving gene therapy was 1.
3 between weeks 12 and 15 months after treatment, and 4.
43 annual bleeding times during the 6-month monitoring period before treatment
.
Forty patients with severe hemophilia type B had a 78% reduction in annualized bleeding rate and a 92%
reduction in annualized infusion rate after treatment.

This gene therapy uses adeno-associated virus (AAV) to deliver the human clotting factor IX gene, thereby helping hemophilia B patients to clot blood and avoid frequent clotting factor transfusions
.
Pfizer introduced the therapy
in 2014 from Spark Therapeutics, which was wholly acquired by Roche in 2019.

Pfizer said the gene therapy was generally well tolerated, with 14 serious adverse events
in 7 patients, or 16% of the total number of patients.
Two of the adverse events (bleeding from gastric ulcers and elevated liver enzymes) were considered treatment-related, and no treatment-related deaths occurred
.
Pfizer said these patients participating in clinical trials will continue to be tested for another 15 years
.

Pfizer plans to disclose more data from the clinical trial in 2023 and discuss the launch of the therapy with regulators earlier this year
.

At present, there are two hemophilia gene therapies approved for marketing worldwide, of which the FDA approved the hemophilia B gene therapy Hemgenix (Etranacogene Dezaparvovec)
developed by UniQure.
The European Union approved Roctavian (Valoctocogene Roxaparvovec), a hemophilia A gene therapy developed by BioMarin Pharmaceutical.

On November 22, 2022, the US FDA approved UniQure's adeno-associated virus (AAV) gene therapy Hemgenix (Etranacogene Dezaparvovec) for the treatment of adult hemophilia
B.
The AAV gene therapy costs up to $3.
5 million, making it the most expensive drug
in the world.

Hemophilia B is an inherited bleeding disorder caused by deficiency or insufficiency
of factor IX.
Blood clotting factor IX is a protein
needed to produce blood clots to stop bleeding.
Symptoms include prolonged or heavy bleeding after injury, surgery or dental procedure; In severe cases, bleeding episodes can occur
spontaneously without a clear cause.
Prolonged bleeding can lead to serious complications such as bleeding in joints, muscles, or internal organs
, including the brain.

Hemophilia is an inherited bleeding disorder
in which genetic mutations cause a lack of clotting factors in the blood.
Hemophilia can be divided into three types: hemophilia A, hemophilia B and hemophilia C, the cause is the deficiency of coagulation factor VIII, IX.
or XI, respectively, the former two are accompanied by X chromosome recessive diseases (so most of the patients are male, women only carry the causative gene mutation, usually mild symptoms), the latter is autosomal incomplete recessive inheritance
.
In hemophilia, type A accounts for about 85%, type B about 15%, and type C is very rare
.

Hemophilia is routinely treated with intravenous coagulation factors that are deficient due to genetic mutations, and factor VIII supplementation is required in patients with hemophilia A, and factor IX.
in patients with type B to maintain adequate coagulation factor levels to prevent bleeding episodes
.

Hemgenix is a disposable gene therapy product that is given
intravenously in a single dose.
The therapy is composed of adeno-associated virus (AAV) carrying the coagulation factor IX.
gene, and after injection into the body, the coagulation factor IX.
gene expresses coagulation factor IX.
in the cell, thereby restoring the level of coagulation factor in the blood and preventing bleeding attacks
.

The safety and efficacy of Hemgenix is based on two clinical trials in 57 adult men aged 18-75 years with severe or moderate hemophilia type B, and its effectiveness is determined
based on a decrease in the patient's annualized bleeding rate (ABR).
The results of clinical trials showed that the annualized bleeding rate (ABR) of patients decreased significantly, and 94% of patients required reinjection of coagulation factors to prevent bleeding events
.

On August 24, 2022, the adeno-associated virus (AAV) gene therapy Roctavian™ (Valoctocogene Roxaparvovec) developed by BioMarin Pharmaceutical received conditional marketing authorization (CMA) from the European Union for the treatment of patients with severe hemophilia A who have no history of factor VIII inhibitors and no detectable antibodies to AAV5
.

In addition, Spark Therapeutics' AAV gene therapy for hemophilia A has completed Phase 1/2 clinical trials
.
Freeline Therapeutics' AAV gene therapy for hemophilia B has also completed Phase 1-2 clinical trials
.