Express Potential blockbuster gene therapy completes FDA marketing application submission

BioMarin Pharmaceutical recently announced that it has re-submitted to the U.
S.
FDA its Biological Product Licensing Application (BLA) for its investigational gene therapy, valoctocogene roxaparvovec, for the treatment of adult patients with
severe hemophilia A.
This submission combines the Company's response to a previous FDA's Complete Response Letter (CRL) dated August 18, 2020, and includes 2-year results from the Phase 3 trial of GENEr8-1 and 5-year follow-up support data
from the Phase 1/2 trial.
BioMarin expects to know by the end of October whether the FDA accepts the results of
its BLA.

Hemophilia A is a rare hereditary bleeding disorder
caused by a lack of coagulation factor VIII.
Deficiency of coagulation factors causes patients to produce insufficient thrombin, leading to coagulation disorders
.
Hemophilia A is characterized by recurrent bleeding and related complications, of which about 80% are joint hemorrhage, the main complications of which are chronic hemorrhagic joint lesions and can lead to severe joint deformities
.
At present, the main treatment for hemophilia A is regular transfusion of coagulation factor VIII, but frequent infusions bring great inconvenience
to the patient's life.

Valoctocogene roxaparvovec is a gene therapy
that uses AAV5 viral vectors to deliver transgenic genes expressing coagulation factor VIII.
It has the advantage that the patient may only need to receive one treatment and the liver cells can continue to express coagulation factor VIII, eliminating the need for long-term prophylactic coagulation factor injections
.
The US FDA granted this gene therapy breakthrough therapy (BTD) and regenerative medicine advanced therapy certification (RMAT)
in 2017 and 2021, respectively.
The therapy is also Orphan Drug Qualified (ODD) by the US FDA and the European Medicines Agency (EMA).

On August 24 this year, the European Commission (EC) approved the conditional marketing
of this gene therapy (trade name: Roctavian) for the treatment of hemophilia A.

The European Commission's decision is based on overall data from Valoctocogene roxaparvovec's extensive clinical development program, including the results
of the global Phase 3 clinical trial GENEr8-1.
The results were recently published
in the New England Journal of Medicine.
The data showed that after a single infusion of valoctocogene roxaparvovec, the use of coagulation factor VIII and the annual bleeding rate requiring treatment were reduced by 99% and 84% (p<0.
001),
respectively, compared to data from the year before enrollment.
Overall, 90% (121/134) of trial participants had no bleeding events requiring treatment or fewer
bleeding events than those received prophylactic treatment with factor VIII.

This submission also contains five-year follow-up support data from the clinical Phase 1/2 dose climb trial using a 6e13 vg/kg dose cohort
.
In addition, BioMarin describes a 15-year long-term extended trial planned for clinical trial participants, as well as two approved registered studies
.

"We are pleased to have achieved the current results on the valoctocogene roxaparvovec development project, and we look forward to working with the FDA to bring this potential transformative therapy to patients with severe hemophilia A in the United States," said Dr.
Hank Fuchs, Global R&D President of BioMarin
.
We are committed to sharing this data with the general public, as well as the long-term data
obtained through our ongoing clinical trials.
This will further give us more insight into
the use of AAV gene therapy to treat severe hemophilia A.
”