BioMarin Announces Positive Phase 3 Gene Therapy Trial Results in Adults with Severe Hemophilia A; Study Met All Primary and Secondary Efficacy…

SAN RAFAEL, Calif., Jan. 10, 2021 /PRNewswire/ --BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced positive topline results from its ongoing global Phase 3 GENEr8-1 study of valoctocogene roxaparvovec, an investigational gene therapy for the treatment of adults with severe hemophilia A. This is the largest global Phase 3 study to date for any gene therapy in any indication, with 134 participants. All participants in the study received a single dose of valoctocogene roxaparvovec and completed a year or more of follow-up.

Data from the GENEr8-1 Phase 3 study with a mean follow-up of 71.6 weeks showed that in the pre-specified primary analysis for Annualized Bleeding Rate (ABR) a single dose of valoctocogene roxaparvovec significantly reduced ABR by 84% from a prospectively collected 4.8 (median 2.8) at baseline to 0.8 (median 0.0) bleeding episodes per year (p-value <0.0001), among a pre-specified group of prior participants in a non-interventional baseline observational study (rollover population; N=112). 80% of participants were bleed-free starting at week five after treatment.

Valoctocogene roxaparvovec also significantly reduced the mean annualized Factor VIII in the rollover population by 99% from 135.9 (median 128.6) to 2.0 (median 0.0) infusions per year (p-value <0.0001).

Table 1: Mean/Median Annualized Bleeding Rate (ABR) and FVIII Infusion Rate in Phase 3 GENEr8-1 Study Rollover Population (N=112) from Week 5 Through Week 52 at Nov. 2020 Cut Off

Phase 3

Rollover Population*

On Factor VIII prophylaxis, before valoctocogene roxaparvovec infusion

N=112

Phase 3

Rollover Population*

After valoctocogene roxaparvovec infusion

N=112

Mean (SD)

Median (IQR)

Mean (SD)

Median (IQR)

Annualized

Bleeding Rate

(bleeding

episodes per

4.8 (6.5)

2.8 (0.0, 7.6)

0.8 (3.0)

0.0 (0.0, 0.0)

Annualized

FVIII Infusion

135.9 (52.0)

128.6 (104.1, 159.9)

2.0 (6.4)

0.0 (0.0, 0.9)

*See study descriptions for patient population information.

At the end of the first year post-infusion with valoctocogene roxaparvovec, participants in the modified intent-to-treat (mITT) population (N=132) had a mean endogenous Factor VIII expression level of 42.9 (SD 45.5, median 23.9) IU/dL, as measured by the chromogenic substrate (CS) assay, supporting the marked clinical benefits observed with abrogation of bleeding episodes and Factor VIII infusion rate. Factor VIII expression declined at a slower rate compared to the Phase 1/2 study, and remained in a range to provide hemostatic efficacy. In a subset of the mITT population that had been dosed at least two years prior to the data cut date (N=17), Factor VIII expression declined from a mean of 42.2(SD 50.9, median 23.9) IU/dL at the end of year one to a mean of 24.4 (SD 29.2, median 14.7) IU/dL at the end of year two with continued hemostatic efficacy demonstrated by a mean ABR of 0.9 (median 0.0) bleeding episodes per year.

Table 2: Factor VIII Activity Levels in 6-Month Intervals

Median Factor

VIII Activity,

IU/dL

Phase 3 Rollover

Population

(N=112)

Mean (SD)

Median

Phase 3 mITT

Subset

Population

(N=17*)

Mean (SD)

Median

Phase 1/2

6e13 vg/kg

Cohort

(N=7)

Mean (SD)

Median

Phase 1/2

4e13 vg/kg

Cohort

(N=6)

Mean (SD)

Median

Week 26

55.1 (57.4)

38.6

43.9 (42.1)

33.8

71.0 (41.6)

61.2

18.0 (8.7)

18.0

Week 52

43.6 (45.3)

24.2

42.2 (50.9)

23.9

63.6 (36.5)

60.3

21.1 (12.3)

23.8

Week 76

27.9 (30.6)

15.8

53.9 (31.2)

50.2

20.6 (15.4)

21.3

Week 104

24.4 (29.2)

14.7

36.4 (26.3)

26.2

12.3 (8.2)

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BioMarin Announces Positive Phase 3 Gene Therapy Trial Results in Adults with Severe Hemophilia A; Study Met All Primary and Secondary Efficacy...