Gene therapy seems safe, effective in hemophilia B

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”