Valrox’s regulatory fate remains hard to call

Two-year data on Biomarin’s valrox show Factor VIII activity continuing to fade, but with the haemophilia A gene therapy still managing to keep bleeding and infusions rates under control, the company is heading to back to the FDA. Whether the US regulator will see enough to change its mind is the big unknown here – it demanded this longer cut of the pivotal GENEr8-1 data alongside a CRL 18 months ago. After being blindsided by the FDA’s rejection, the sellside is now more cautious about the project’s outlook. Analysts at Stifel say the regulatory outcome is hard to handicap given valrox’s history, a recent “cautiously framed gene therapy adcom”, and a number of clinical holds in the space. For analysts at Evercore ISI, the biggest issue is a preclinical cancer signal in immune compromised rodents seen with Biomarin’s PKU gene therapy, which might mean valrox receives a narrow approved indication, at least initially. Either way, the data show that valrox is far from a “once and done” therapy, and its real durability beyond three years is unclear. If regulators are comfortable with safety perhaps this will not matter, but the uncertainty promises to make negotiating a price tag equally as complex.

Two-year data from pivotal GENEr8-1 trial of valrox (Roctavian) 
    Year 1 Year 2 Year 3
    N=132/112* N=132/112* N=17**
FVIII activity (chromogenic)  Mean 42.8 23.0 16.8
  Median 23.9 11.8 9.3
Annualised bleeding rate (per year) Mean 0.9 0.7 0.6
  Median 0 0 0
Annualised FVIII infusions per year  Mean 1.5 3.4 n/a
  Median 0 0 n/a
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 utilization endpoints. **mITT subset population dosed >3 years prior to data cut. Source: Biomarin press release.

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