Print Friendly, PDF & Email

K. John Pasi, MBChB, PhD
© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”


The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

Print Friendly, PDF & Email