Hemophilia A patients are at risk of spontaneous bleeds because they lack clotting factor VIII, a protein necessary for coagulation. Since uncontrolled bleeding is life-threatening, nearly half of the 150,000 patients with this genetic disorder receive prophylactic infusions of factor VIII every week. The cost of these infusions can easily exceed $200,000 per year, and since the life expectancy for children with hemophilia A is normal, lifetime spending is well into the millions of dollars. 

Clearly, there's a lot of room for improvement in terms of quality of life and costs.

One solution could be gene therapies that deliver functional genes to these patients, restoring factor VIII production and possibly eliminating or significantly reducing the need for infusions. Although gene therapies for hemophilia aren't available yet, the latest results from a phase 3 study of BioMarin's (NASDAQ:BMRN) valoctocogene roxaparvovec, or ValRox, suggest they're on the way. 

A female doctor giving a thumbs up sign.

Image source: Getty Images.

What's the latest news? 

On May 28, BioMarin revealed interim phase 3 data for a subset of patients who received a single 6e13 vg/kg dose of ValRox. At the April 30 cut-off for data analysis, seven of 16 study people who had reached week 26 had achieved factor VIII activity levels at or above 40 international units per deciliter (IU/dL). Overall, the mean factor VIII level in these 16 patients was 36 IU/dL and the median was 33 IU/dL from week 23 to week 26.

Importantly, the estimated median and average bleed rates for all 16 patients eligible for data collection was zero and 1.5, respectively, an 85% improvement from baseline bleed rates at the time of trial enrollment. The median and average annualized use of factor VIII fell 84% and 94%, respectively, for these patients.

ValRox performance within this subgroup has BioMarin targeting a filing for accelerated Food and Drug Administration approval soon. An update of its timing for such a filing is expected next quarter.

Is ValRox durable?

The data suggests ValRox could be a game-changer. Severe hemophiliacs factor VIII activity is typically less than one IU/dL, and clinicians typically view factor VIII activity of 12 IU/dL as the level at which bleeding risk is limited. Levels between 5 IU/dL and 40 IU/dL are characterized as "mild" hemophilia that's unlikely to result in spontaneous bleeds. 

The ideal goal for a gene therapy for severe hemophilia would be maintaining levels above 40 IU/dL. However, levels above 12 could still be considered significant. Levels of 5 could also be viewed as a win since they would transform severe cases into mild cases less likely to need prophylactic infusions.

By those measures, ValRox is a success. However, the big question is if ValRox benefits will prove long-lasting. That question intensified today when management also updated results from patients participating in its phase 1/2 study. At the three-year mark, factor VIII levels of these patients were an average and median of 32.7 IU/dL and 19.9 IU/dl, respectively. In May 2018, the average and median were 36.4 IU/dL and 26.2 IU/dL, respectively, at the two-year mark. The drop-off is one big reason BioMarin's share price slipped despite the phase 3 results and plans to file for approval.

A person looking through a microscope.

Image source: Getty Images.

Does it matter?

Probably not.

The phase 1/2 data still show levels remain in line with mild cases and that bleeds remain well controlled at the three-year mark. Specifically, the median annualized bleed rate was zero and the average annualized bleed rate was only 0.7 in year three. That was good enough for management to say that "more conservative statistical modeling anticipates that bleeding control will be maintained for at least eight years after gene transfer."

Since bleed risk and the need of prophylactic treatment are where the rubber meets the road for patients, doctors, and insurers, ValRox's ability to control bleeding for years will likely be viewed by all three as a remarkable advance. Of course, BioMarin needs to win FDA approval before ValRox can be widely available, and there's no guarantee that the FDA will green-light it. Nevertheless, I think ValRox is likely to make its way through the FDA gantlet based on this data. If I'm right, it could help change treatment forever for hemophilia A patients.