Valrox shows signs of plateauing

After the big fades in factor VIII levels previously seen with Biomarin’s haemophilia A gene therapy contender valoctocogene roxaparvovec (valrox), a less pronounced drop-off at three years will be a relief to investors. Still, it is notable that analysts are now talking up the prospects of the project, once touted as a once-and-done option, lasting beyond five years. And SVB estimated that around 11 patients returned to FVIII prophylaxis at the end of year three, “slightly more than we wanted to see”. This number only looks set to increase as more patients dip below FVIII activity of 15IU/dl. Another question is whether the three-year data, requested by the FDA, will constitute a major amendment to Biomarin’s submission, delaying an approval decision beyond valrox’s current Pdufa date of March 31. On the plus side, the FDA completed a manufacturing site inspection in early December. Valrox was approved in the EU in August as Roctavian, but there payers are the main barrier. Biomarin has still not started dosing commercially in Germany, something it had hoped to do last quarter, but has now signed an outcomes-based agreement with one of the three largest health insurance groups there.

Three-year data from pivotal GENEr8-1 trial of valrox 
  Year 1 Year 2 Year 3 Year 4
N=132/112* N=132/112* N=132/112* N=17**
FVIII activity (chromogenic)  Mean 42.8 23.0 18.8 15.2
Median 23.9 11.8 8.4 7.4
Annualised bleeding rate (per year) Mean 0.9 0.7 1.0 0.8
Median 0.0 0.0 0.0 0.0
Annualised FVIII infusions per year  Mean 1.5 3.4 8.4 11.1
Median 0.0 0.0 0.0 0.0
Note: results for 6e13vg/kg dose only. *mITT population (N=132) for FVIII activity endpoint; rollover population (N=112) for annualised bleeding rate and annualised FVIII utilisation endpoints (2 pts discontinued before reaching yr3). **mITT subset population dosed >4 years before data cut (1 pt discontinued before reaching yr4). Source: Biomarin press release.

Share This Article