Spark Therapeutics and Pfizer Inc. announced that Lindsey A. George, M.D., a hematologist and attending physician at the Children’s Hospital of Philadelphia and lead investigator in the phase 1/2 clinical trial of SPK-9001 for treatment of haemophilia B, will present an updated dataset from the ongoing phase 1/2 clinical trial of SPK-9001 at the 58th American Society of Hematology (ASH) Annual Meeting, to be held December 3-6, 2016 in San Diego.

The conference abstract, including a plot of factor IX activity levels (as a % of normal) expressed over time by the first seven participants as of August 4, 2016, was made available.
 
The results are from the first seven participants who received a single administration of investigational SPK-9001 at a dose of 5 x 1011 vector genomes (vg)/kg body weight. Four of the seven participants had reached greater than 12 weeks post-vector administration at the time of abstract submission; those four participants experienced consistent and sustained factor IX activity levels, with a mean greater than 30% of normal, with no sustained elevation in liver enzyme levels.
 
Spark Therapeutics and Pfizer report that one participant, who had not reached 12 weeks post-vector administration, manifested an immune response to the adeno-associated virus (AAV) capsid, accompanied by a drop in factor IX activity level, and was put on a tapering course of corticosteroids. Despite the immune response and decline in factor IX activity level, this participant has not had any bleeds or required replacement factor. No other participant has required the use of corticosteroids. The companies expect to announce updated trial results at the upcoming ASH Annual Meeting in December.
 
None of the participants received infusions of factor IX concentrates to prevent bleeding events. One precautionary infusion took place in one participant two days after administration of SPK-9001 due to a suspected ankle bleed.
 
"These initial observations are encouraging, underscoring the potential of investigational SPK-9001 to deliver a potentially consistent, sustained and therapeutically meaningful level of factor IX activity through one administration," said Dr. George. “Participants in the trial did not require prophylactic factor IX infusions to prevent bleeding, including one participant who we have followed for more than eight months as of the data cutoff. We look forward to reporting additional data as we continue to document the longer-term experience with SPK-9001.”
 
As of August 4, 2016, total consumption of clotting factor in all seven trial participants during a cumulative 724 days following vector administration was reduced by more than 540,000 international units, based on their pre-trial usage levels. Additionally, to date six of seven participants reported increased physical activity and improved quality of life, based on the Haemophilia Quality of Life Questionnaire for Adults, a validated instrument that measures health-related quality of life in adults with haemophilia.
 
Hemophilia, a rare genetic bleeding disorder that causes the blood to take a long time to clot as a result of a deficiency in one of several blood clotting factors, is common almost exclusively in males. People with haemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. People with severe haemophilia often bleed spontaneously into their muscles or joints. The incidence of haemophilia B is one in 25,000 male births. People with haemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B is also called congenital factor IX deficiency or Christmas disease. Current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with haemophilia.

Spark Therapeutics' proprietary technology platform for selecting, designing, manufacturing and formulating highly optimized gene therapies was applied to developing compounds in the SPK-FIX program. The SPK-FIX program leverages a long history of haemophilia gene therapy research and clinical development conducted by Spark Therapeutics and its founding scientific team over nearly three decades. SPK-9001 is a novel bio-engineered adeno-associated virus (AAV) capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX. SPK-9001 is being developed under a collaboration with Pfizer. Spark Therapeutics and Pfizer entered into a collaboration in 2014 for the SPK-FIX program, including SPK-9001, under which Spark Therapeutics is responsible for conducting all phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration. SPK-9001 has received breakthrough therapy and orphan product designations from the US Food and Drug Administration.