Gene transfer for hemophilia B shows progress
“Clinically, what this has meant for this man is he is now off his prophylaxis, he has no longer had breakthrough bleeding events, and he has not required factor for any reason,” Dr George said.
Capsid immune responses
Seven patients had less than 1:1 Spark100 neutralizing antibody at baseline and did not require steroids.
Their mean steady-state FIX activity was 31.9 + 7.4% at a follow-up of 12 to 52 weeks. Their liver function tests remained less than 1.5 times the upper limit of normal.
Two patients had capsid immune responses requiring steroid treatment.
One patient, a 45-year-old male, had a FIX:C of 1.9%, experienced 49 bleeding events prior to receiving SPK-9001, and was treated on-demand.
After SPK-9001, he had no vector-related adverse events, received a course of prednisone, and, at 20 weeks follow-up, had experienced no bleeding events and did not require factor use.
The second patient who had a capsid immune response was 36 years of age and on FIX prophylaxis. He had a history of HCV and no history of HIV.
After SPK-9001, he experienced no bleeding and required no factor use. He had grade 1 transaminase toxicity, which returned to within normal limits.
He is taking 40 mg prednisone daily and has stable FIX:C activity at 49 days after vector infusion.
Overall transgene-derived FIX activity
At a follow-up of 7 to 52 weeks, for a cumulative 238 weeks for all patients, their mean steady-state FIX activity was 28.3 + 10.0% of normal.
They had no vector or procedure-related unexpected adverse events, although 1 patient had transient grade 1 transaminase toxicity.
No patient developed FIX alloinhibitory antibodies.
One patient had FIX:C activity of 68% of normal at 7 weeks, and the first patient infused had 33% FIX:C activity at 52 weeks.
The transgene-derived FIX activity resulted in a significant reduction in bleeding events (P<0.05) and factor use (P<0.05). All patients stopped their prophylaxis.
The researchers recommend a larger cohort and continued observation to confirm these results.
Dr George noted that SPK-9001 has received breakthrough therapy designation from the US Food and Drug Administration. 
*Information presented at the meeting differs from the abstract.
