Gene therapy reduces ABR, AIR in hemophilia B

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

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

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

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

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

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

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”