NEJM: BioMarin's Phase 3 clinical trial results of AAV therapy for hemophilia released, with positive and sustained effects

In 1884, when Queen Victoria's granddaughter Alex was in Russia to attend her sister's wedding, she fell in love at first sight with Nicholas, son of the then Russian Tsar Alexander III
.

And this love at first sight has become the direct fuse of Russia's demise

Ten years later, Alex was engaged to Nikolai, who became the new Tsar in the same year
.

Another 10 years later, their son Alexei was born

In order to cure Alexei, the tsar trusted and reused the witch doctor Rasputin.
Under Rasputin's absurd intervention in the Russian government, Russia suffered from internal and external troubles, and finally the "October Revolution" broke out in 1917.
The curtain ended, and the Soviet regime took to the stage of history
.

We now know that Alexei's strange disease is actually hemophilia, specifically hemophilia B, which is an X-chromosome recessive genetic disease.
Her mother, Alex, inherited from Queen Victoria has a mutation in a disease-causing gene and therefore does not develop the disease, while males have only one X chromosome and therefore develop the disease with one mutation
.

Hemophilia spread among royal families due to intermarriage among European royal families, so it is also known as " royal disease "

royal disease

Hemophilia , the reason why bleeding is easy and difficult to stop, is due to a genetic mutation that causes a lack of clotting factors in the blood, resulting in a blood clotting disorder
.

Hemophilia can be divided into three types: hemophilia A, hemophilia B and hemophilia C, which are caused by deficiency of coagulation factors VIII, IX or XI, respectively, the former two being recessive with X chromosome Genetic disease, the latter is an autosomal incomplete recessive inheritance

Hemophilia

Hemophilia patients are usually restricted from activities for a long time because they are easy to bleed and extremely difficult to clot, so they cannot go to school or go out to play normally
.

Because hemophilia patients are very easy to bleed and extremely difficult to clot, they are usually restricted from activities for a long time, unable to go to school, go out to play, etc.
, and even some severe hemophilia patients need to stay in bed for a long time, and their quality of life is extremely poor.

As a genetic disease caused by gene mutation, gene therapy is almost the only effective treatment for hemophilia
.

Since hemophilia A accounts for the vast majority of hemophilia, research has also focused on the safe delivery of factor VIII into patient cells through gene therapy

On March 17, 2022, the results of the Phase 3 clinical trial of Valoctocogene Roxaparvovec, an AAV gene therapy developed by BioMarin Pharmaceutical for the treatment of adults with severe hemophilia A, were officially released in the New England Journal of Medicine (NEJM)
.

On March 17, 2022, the results of the Phase 3 clinical trial of Valoctocogene Roxaparvovec, an AAV gene therapy developed by BioMarin Pharmaceutical for the treatment of adults with severe hemophilia A, were officially released in the New England Journal of Medicine (NEJM)
.

The AAV gene therapy delivers cDNA of human coagulation factor VIII through adeno-associated virus type 5 (AAV) at an injection dose of 6×10E13vg/kg, which was determined based on phase 2 clinical trial data
.

This phase 3 clinical trial, involving 134 adult patients with hemophilia A, is also the largest clinical trial of hemophilia gene therapy in the world.
Patients were followed up for at least one year after treatment (mean follow-up time 71.
6 weeks)
.

The results showed that 80% of patients had no bleeding events from the fifth week after treatment, and after a single injection treatment, the annualized bleeding frequency of patients decreased from an average of 4.
8 at baseline (median 2.
8) to an annual average of 2.
8.
0.
8 times (median 0.
0 times), a decline rate of 83.
8%
.

The treatment also reduced the patient's annualized factor VIII infusion rate very significantly, from an annual mean of 135.
9 infusions at baseline (median 128.
6) to an annual mean of 2.
0 (median 0.
0 times), with a decline rate of 98.
6%
.

During the follow-up period, the coagulation factor VIII activity in the patient remained relatively stable for a long time
.

All 134 patients experienced at least one adverse event
.

Serious adverse events were reported in 22 (16.

Data from this phase 3 clinical trial show that in patients with severe hemophilia A, Valoctocogene Roxaparvovec therapy can significantly restore the production of coagulation factor VIII in patients and maintain long-term stability, significantly reducing the patient's bleeding and frequent coagulation factors Ⅷ infusion therapy

In addition to BioMarin, Roche's subsidiary Spark Therapeutics' AAV gene therapy for hemophilia A has also achieved good results.

Original source:

Original source:

Margareth C.

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