Therapy increases factor IX activity in hemophilia B

Image by Spencer Phillips

SCOTTSDALE, ARIZONA—The investigational therapy SPK-9001 delivers “consistent and sustained” increases in factor IX (FIX) activity in patients with hemophilia B, according to researchers.

All 10 subjects who received SPK-9001 in a phase 1/2 trial have consistently achieved the targeted therapeutic range of FIX activity.

There have been no confirmed bleeds, and 9 of the subjects have not received any infusions of FIX therapy since receiving SPK-9001.

SPK-9001 reduced the patients’ annualized bleeding rate by 96% and the annualized infusion rate by 99%.

Adam Cuker, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and his colleagues presented these results at the Hemostasis and Thrombosis Research Society 2017 Scientific Symposium.

The trial is sponsored by Spark Therapeutics and Pfizer, the companies developing SPK-9001.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human FIX variant enabling endogenous production of FIX.

In the phase 1/2 trial, 10 hemophilia B patients received a single administration of SPK-9001 (5 x 10¹¹ vector genomes/kg body weight).

As of the data cutoff (March 24, 2017), 9 of the 10 patients have not taken FIX concentrates to prevent or control bleeding events since they received SPK-9001.

One patient with severe joint disease has self-administered infusions. The patient self-infused FIX therapy for a suspected ankle bleed on day 2 after receiving SPK-9001 and self-administered precautionary infusions another 9 times between December 2, 2016, and January 2, 2017, for persistent knee pain. The patient has not used additional FIX therapy since January 2.

For all 10 patients, the mean steady-state FIX activity level 12 weeks after SPK-9001 administration was a sustained 33% (range as of the data cutoff: 14% to 81%).

Based on individual patient history prior to the study, the annualized bleeding rate was reduced by 96% to a mean of 0.39 annual bleeds, compared with 9.2 bleeds before SPK-9001 administration.

The annualized infusion rate was reduced 99% to a mean of 0.98 annual infusions, compared with 68.5 infusions before SPK-9001 administration.

To date, no serious adverse events have been reported, including no FIX inhibitors and no thrombotic events.

Two of the 10 patients experienced an asymptomatic, transient elevation in liver enzymes, or decline in FIX activity, potentially indicative of an immune response to the Spark100 vector capsid, that occurred several weeks post-infusion.

Both patients received a tapering dose of oral corticosteroids, after which their alanine aminotransferase levels returned to baseline.

The FIX activity level of one of these patients has stabilized at approximately 15% for more than 9 weeks post-corticosteroid use. The other patient had a FIX activity level between 70% and 80% upon completion of steroid use. 

Image by Spencer Phillips

SCOTTSDALE, ARIZONA—The investigational therapy SPK-9001 delivers “consistent and sustained” increases in factor IX (FIX) activity in patients with hemophilia B, according to researchers.

All 10 subjects who received SPK-9001 in a phase 1/2 trial have consistently achieved the targeted therapeutic range of FIX activity.

There have been no confirmed bleeds, and 9 of the subjects have not received any infusions of FIX therapy since receiving SPK-9001.

SPK-9001 reduced the patients’ annualized bleeding rate by 96% and the annualized infusion rate by 99%.

Adam Cuker, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and his colleagues presented these results at the Hemostasis and Thrombosis Research Society 2017 Scientific Symposium.

The trial is sponsored by Spark Therapeutics and Pfizer, the companies developing SPK-9001.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human FIX variant enabling endogenous production of FIX.

In the phase 1/2 trial, 10 hemophilia B patients received a single administration of SPK-9001 (5 x 10¹¹ vector genomes/kg body weight).

As of the data cutoff (March 24, 2017), 9 of the 10 patients have not taken FIX concentrates to prevent or control bleeding events since they received SPK-9001.

One patient with severe joint disease has self-administered infusions. The patient self-infused FIX therapy for a suspected ankle bleed on day 2 after receiving SPK-9001 and self-administered precautionary infusions another 9 times between December 2, 2016, and January 2, 2017, for persistent knee pain. The patient has not used additional FIX therapy since January 2.

For all 10 patients, the mean steady-state FIX activity level 12 weeks after SPK-9001 administration was a sustained 33% (range as of the data cutoff: 14% to 81%).

Based on individual patient history prior to the study, the annualized bleeding rate was reduced by 96% to a mean of 0.39 annual bleeds, compared with 9.2 bleeds before SPK-9001 administration.

The annualized infusion rate was reduced 99% to a mean of 0.98 annual infusions, compared with 68.5 infusions before SPK-9001 administration.

To date, no serious adverse events have been reported, including no FIX inhibitors and no thrombotic events.

Two of the 10 patients experienced an asymptomatic, transient elevation in liver enzymes, or decline in FIX activity, potentially indicative of an immune response to the Spark100 vector capsid, that occurred several weeks post-infusion.

Both patients received a tapering dose of oral corticosteroids, after which their alanine aminotransferase levels returned to baseline.

The FIX activity level of one of these patients has stabilized at approximately 15% for more than 9 weeks post-corticosteroid use. The other patient had a FIX activity level between 70% and 80% upon completion of steroid use. 

Image by Spencer Phillips

SCOTTSDALE, ARIZONA—The investigational therapy SPK-9001 delivers “consistent and sustained” increases in factor IX (FIX) activity in patients with hemophilia B, according to researchers.

All 10 subjects who received SPK-9001 in a phase 1/2 trial have consistently achieved the targeted therapeutic range of FIX activity.

There have been no confirmed bleeds, and 9 of the subjects have not received any infusions of FIX therapy since receiving SPK-9001.

SPK-9001 reduced the patients’ annualized bleeding rate by 96% and the annualized infusion rate by 99%.

Adam Cuker, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and his colleagues presented these results at the Hemostasis and Thrombosis Research Society 2017 Scientific Symposium.

The trial is sponsored by Spark Therapeutics and Pfizer, the companies developing SPK-9001.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human FIX variant enabling endogenous production of FIX.

In the phase 1/2 trial, 10 hemophilia B patients received a single administration of SPK-9001 (5 x 10¹¹ vector genomes/kg body weight).

As of the data cutoff (March 24, 2017), 9 of the 10 patients have not taken FIX concentrates to prevent or control bleeding events since they received SPK-9001.

One patient with severe joint disease has self-administered infusions. The patient self-infused FIX therapy for a suspected ankle bleed on day 2 after receiving SPK-9001 and self-administered precautionary infusions another 9 times between December 2, 2016, and January 2, 2017, for persistent knee pain. The patient has not used additional FIX therapy since January 2.

For all 10 patients, the mean steady-state FIX activity level 12 weeks after SPK-9001 administration was a sustained 33% (range as of the data cutoff: 14% to 81%).

Based on individual patient history prior to the study, the annualized bleeding rate was reduced by 96% to a mean of 0.39 annual bleeds, compared with 9.2 bleeds before SPK-9001 administration.

The annualized infusion rate was reduced 99% to a mean of 0.98 annual infusions, compared with 68.5 infusions before SPK-9001 administration.

To date, no serious adverse events have been reported, including no FIX inhibitors and no thrombotic events.

Two of the 10 patients experienced an asymptomatic, transient elevation in liver enzymes, or decline in FIX activity, potentially indicative of an immune response to the Spark100 vector capsid, that occurred several weeks post-infusion.

Both patients received a tapering dose of oral corticosteroids, after which their alanine aminotransferase levels returned to baseline.

The FIX activity level of one of these patients has stabilized at approximately 15% for more than 9 weeks post-corticosteroid use. The other patient had a FIX activity level between 70% and 80% upon completion of steroid use.