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Gene therapy shows promise for severe hemophilia A
Image by Spencer Phillips
ORLANDO—An investigational gene therapy can safely reduce bleeding in patients with severe hemophilia A, a phase 1/2 study suggests.
The therapy is BMN 270, a recombinant adeno-associated virus (AAV) vector coding for human coagulation factor VIII (FVIII).
Six of the 7 patients treated with the highest dose of BMN 270 had FVIII levels above 50%, and the number of bleeding events fell substantially from baseline.
None of the patients developed inhibitors to FVIII, there were no serious adverse events, and none of the patients discontinued the therapy due to safety reasons.
John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented the results of this study in a late-breaking oral presentation at the World Federation of Hemophilia 2016 World Congress.* The research was funded by BioMarin Pharmaceutical Inc.
This phase 1/2 dose-escalation study was designed to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
The primary endpoints are to assess the safety of a single dose of BMN 270 and the change from baseline of FVIII expression level at 16 weeks after infusion.
Secondary endpoints include assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses. Patients will be monitored for safety and durability of effect for 5 years.
Thus far, 9 patients with severe hemophilia A have received a single dose of BMN 270—1 at 6×1012 vg/kg, 1 at 2×1013 vg/kg, and 7 at 6 x 1013 vg/kg.
As of the July 6 data cutoff, post-treatment follow-up ranges from 12 weeks to 28 weeks.
Safety
The most common adverse events were arthralgia (9 events in 6 subjects), contusion (6 events in 3 subjects), back pain (4 events in 3 subjects), and ALT elevation (6 events in 6 subjects).
No clinically relevant sustained rises in ALT levels or other markers of liver toxicity have been observed.
The maximum ALT levels were between 23 U/L and 82 U/L (less than 2 times the upper limit of normal, which is 43 U/L for the central laboratory in this study) approximately 12 weeks after gene delivery and generally declined over the next few weeks. ALT rises have not been associated with any decrease in FVIII levels.
A steroid regimen administered to all high-dose patients has been well-tolerated. Patients are successfully tapering off of steroids. Two patients have been off steroid therapy for up to 2.5 weeks, with no adverse impact on FVIII expression or ALT levels.
Efficacy
The patient treated at the lowest dose (6×1012 vg/kg) had no change from baseline in FVIII levels. The patient treated at the mid-dose (2×1013 vg/kg) had a stable FVIII activity level greater than 2 IU/dL for more than 28 weeks.
All 7 patients treated at the highest dose (6×1013 vg/kg) had FVIII activity levels greater than 10 IU/dL after week 10.
As of each patient’s most recent reading, 6 of the 7 patients in the high-dose group had FVIII levels above 50%, as a percentage calculated based on the numbers of IU/dL. The seventh patient had levels above 10%.
Four patients who have been followed the longest had a mean FVIII level of 146% at their 20-week visit. Two patients with FVIII levels above 200% had no unexpected events or need for medical intervention.
For the 7 patients treated at the high dose, the median annualized bleeding rate measured from the day of gene transfer to the data cutoff fell from 20 to 5.
After week 7 post-infusion, there were no bleeds in 6 of the 7 patients. There were 10 bleeds from weeks 0 through 2 post-infusion, 7 bleeds from weeks 3 through 8, and 2 bleeds from weeks 9 through 28. From weeks 2 through 28, all but 1 bleed occurred in a single subject who is the lowest responder.
All of the patients in the high-dose cohort have switched to receiving FVIII therapy on-demand. Six of them were previously receiving FVIII therapy as prophylaxis.
“These data provide strong proof-of-concept evidence that restoration of clotting function may be achieved by gene therapy,” Dr Pasi said. “For the first time, patients have reason to hope to avoid bleeding and the opportunity to live a normal life.” 
Image by Spencer Phillips
ORLANDO—An investigational gene therapy can safely reduce bleeding in patients with severe hemophilia A, a phase 1/2 study suggests.
The therapy is BMN 270, a recombinant adeno-associated virus (AAV) vector coding for human coagulation factor VIII (FVIII).
Six of the 7 patients treated with the highest dose of BMN 270 had FVIII levels above 50%, and the number of bleeding events fell substantially from baseline.
None of the patients developed inhibitors to FVIII, there were no serious adverse events, and none of the patients discontinued the therapy due to safety reasons.
John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented the results of this study in a late-breaking oral presentation at the World Federation of Hemophilia 2016 World Congress.* The research was funded by BioMarin Pharmaceutical Inc.
This phase 1/2 dose-escalation study was designed to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
The primary endpoints are to assess the safety of a single dose of BMN 270 and the change from baseline of FVIII expression level at 16 weeks after infusion.
Secondary endpoints include assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses. Patients will be monitored for safety and durability of effect for 5 years.
Thus far, 9 patients with severe hemophilia A have received a single dose of BMN 270—1 at 6×1012 vg/kg, 1 at 2×1013 vg/kg, and 7 at 6 x 1013 vg/kg.
As of the July 6 data cutoff, post-treatment follow-up ranges from 12 weeks to 28 weeks.
Safety
The most common adverse events were arthralgia (9 events in 6 subjects), contusion (6 events in 3 subjects), back pain (4 events in 3 subjects), and ALT elevation (6 events in 6 subjects).
No clinically relevant sustained rises in ALT levels or other markers of liver toxicity have been observed.
The maximum ALT levels were between 23 U/L and 82 U/L (less than 2 times the upper limit of normal, which is 43 U/L for the central laboratory in this study) approximately 12 weeks after gene delivery and generally declined over the next few weeks. ALT rises have not been associated with any decrease in FVIII levels.
A steroid regimen administered to all high-dose patients has been well-tolerated. Patients are successfully tapering off of steroids. Two patients have been off steroid therapy for up to 2.5 weeks, with no adverse impact on FVIII expression or ALT levels.
Efficacy
The patient treated at the lowest dose (6×1012 vg/kg) had no change from baseline in FVIII levels. The patient treated at the mid-dose (2×1013 vg/kg) had a stable FVIII activity level greater than 2 IU/dL for more than 28 weeks.
All 7 patients treated at the highest dose (6×1013 vg/kg) had FVIII activity levels greater than 10 IU/dL after week 10.
As of each patient’s most recent reading, 6 of the 7 patients in the high-dose group had FVIII levels above 50%, as a percentage calculated based on the numbers of IU/dL. The seventh patient had levels above 10%.
Four patients who have been followed the longest had a mean FVIII level of 146% at their 20-week visit. Two patients with FVIII levels above 200% had no unexpected events or need for medical intervention.
For the 7 patients treated at the high dose, the median annualized bleeding rate measured from the day of gene transfer to the data cutoff fell from 20 to 5.
After week 7 post-infusion, there were no bleeds in 6 of the 7 patients. There were 10 bleeds from weeks 0 through 2 post-infusion, 7 bleeds from weeks 3 through 8, and 2 bleeds from weeks 9 through 28. From weeks 2 through 28, all but 1 bleed occurred in a single subject who is the lowest responder.
All of the patients in the high-dose cohort have switched to receiving FVIII therapy on-demand. Six of them were previously receiving FVIII therapy as prophylaxis.
“These data provide strong proof-of-concept evidence that restoration of clotting function may be achieved by gene therapy,” Dr Pasi said. “For the first time, patients have reason to hope to avoid bleeding and the opportunity to live a normal life.”
Image by Spencer Phillips
ORLANDO—An investigational gene therapy can safely reduce bleeding in patients with severe hemophilia A, a phase 1/2 study suggests.
The therapy is BMN 270, a recombinant adeno-associated virus (AAV) vector coding for human coagulation factor VIII (FVIII).
Six of the 7 patients treated with the highest dose of BMN 270 had FVIII levels above 50%, and the number of bleeding events fell substantially from baseline.
None of the patients developed inhibitors to FVIII, there were no serious adverse events, and none of the patients discontinued the therapy due to safety reasons.
John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented the results of this study in a late-breaking oral presentation at the World Federation of Hemophilia 2016 World Congress.* The research was funded by BioMarin Pharmaceutical Inc.
This phase 1/2 dose-escalation study was designed to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
The primary endpoints are to assess the safety of a single dose of BMN 270 and the change from baseline of FVIII expression level at 16 weeks after infusion.
Secondary endpoints include assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses. Patients will be monitored for safety and durability of effect for 5 years.
Thus far, 9 patients with severe hemophilia A have received a single dose of BMN 270—1 at 6×1012 vg/kg, 1 at 2×1013 vg/kg, and 7 at 6 x 1013 vg/kg.
As of the July 6 data cutoff, post-treatment follow-up ranges from 12 weeks to 28 weeks.
Safety
The most common adverse events were arthralgia (9 events in 6 subjects), contusion (6 events in 3 subjects), back pain (4 events in 3 subjects), and ALT elevation (6 events in 6 subjects).
No clinically relevant sustained rises in ALT levels or other markers of liver toxicity have been observed.
The maximum ALT levels were between 23 U/L and 82 U/L (less than 2 times the upper limit of normal, which is 43 U/L for the central laboratory in this study) approximately 12 weeks after gene delivery and generally declined over the next few weeks. ALT rises have not been associated with any decrease in FVIII levels.
A steroid regimen administered to all high-dose patients has been well-tolerated. Patients are successfully tapering off of steroids. Two patients have been off steroid therapy for up to 2.5 weeks, with no adverse impact on FVIII expression or ALT levels.
Efficacy
The patient treated at the lowest dose (6×1012 vg/kg) had no change from baseline in FVIII levels. The patient treated at the mid-dose (2×1013 vg/kg) had a stable FVIII activity level greater than 2 IU/dL for more than 28 weeks.
All 7 patients treated at the highest dose (6×1013 vg/kg) had FVIII activity levels greater than 10 IU/dL after week 10.
As of each patient’s most recent reading, 6 of the 7 patients in the high-dose group had FVIII levels above 50%, as a percentage calculated based on the numbers of IU/dL. The seventh patient had levels above 10%.
Four patients who have been followed the longest had a mean FVIII level of 146% at their 20-week visit. Two patients with FVIII levels above 200% had no unexpected events or need for medical intervention.
For the 7 patients treated at the high dose, the median annualized bleeding rate measured from the day of gene transfer to the data cutoff fell from 20 to 5.
After week 7 post-infusion, there were no bleeds in 6 of the 7 patients. There were 10 bleeds from weeks 0 through 2 post-infusion, 7 bleeds from weeks 3 through 8, and 2 bleeds from weeks 9 through 28. From weeks 2 through 28, all but 1 bleed occurred in a single subject who is the lowest responder.
All of the patients in the high-dose cohort have switched to receiving FVIII therapy on-demand. Six of them were previously receiving FVIII therapy as prophylaxis.
“These data provide strong proof-of-concept evidence that restoration of clotting function may be achieved by gene therapy,” Dr Pasi said. “For the first time, patients have reason to hope to avoid bleeding and the opportunity to live a normal life.”
mAb could change treatment of hemophilia A, doc says
Photo by Linda Bartlett
ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.
Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.
There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.
None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.
Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.
The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.
Patients and treatment
The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.
The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).
There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.
For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.
The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.
One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.
Safety
The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).
The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.
There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.
There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.
Efficacy
In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).
In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).
In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).
Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.
Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.
Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.
Photo by Linda Bartlett
ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.
Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.
There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.
None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.
Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.
The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.
Patients and treatment
The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.
The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).
There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.
For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.
The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.
One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.
Safety
The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).
The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.
There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.
There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.
Efficacy
In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).
In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).
In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).
Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.
Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.
Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.
Photo by Linda Bartlett
ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.
Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.
There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.
None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.
Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.
The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.
Patients and treatment
The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.
The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).
There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.
For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.
The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.
One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.
Safety
The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).
The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.
There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.
There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.
Efficacy
In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).
In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).
In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).
Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.
Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.
Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.
How hemophilia B impacts education, work
ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.
Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.
More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.
These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.
The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.
The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)
In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.
Education
Most of the patients (71%) had at least some college education, and 17% had graduated from college.
A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.
Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).
Career
Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.
Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.
Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.
Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.
Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).
Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.
“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.
“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”
ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.
Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.
More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.
These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.
The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.
The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)
In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.
Education
Most of the patients (71%) had at least some college education, and 17% had graduated from college.
A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.
Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).
Career
Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.
Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.
Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.
Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.
Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).
Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.
“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.
“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”
ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.
Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.
More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.
These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.
The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.
The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)
In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.
Education
Most of the patients (71%) had at least some college education, and 17% had graduated from college.
A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.
Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).
Career
Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.
Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.
Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.
Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.
Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).
Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.
“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.
“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”
Children under 6 with factor XIII deficiency had no major bleeds with recombinant product
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
AT WFH 2016 WORLD CONGRESS
Key clinical point: A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency.
Major finding: No bleeds occurred within a year in children with factor XIII-A subunit deficiency.
Data source: Open-label international phase III trial in three boys and three girls under age 6.
Disclosures: Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
Patients can safely receive less FVIII, study suggests
ORLANDO—It may be possible for hemophilia patients to receive less factor VIII (FVIII) without increasing their risk of bleeding, according to a study presented at the World Federation of Hemophilia 2016 World Congress.
The study1 showed that hemophilia A patients who received prophylactic FVIII from the home infusion provider Option Care received 6 fewer units of FVIII per week than patients receiving prophylactic FVIII from specialty pharmacies.
This translated to a cost savings of more than $20,000 per patient each year.
The home infusion patients also had a lower annual bleed rate (ABR) than what is typically observed with intensive prophylaxis protocols in hemophilia, according to previous studies.
“By working with prescribers to closely monitor bleeds and collaborate on clinically appropriate optimization of treatment dose, Option Care’s utilization of factor VIII is less than the average with excellent outcomes,” said Joan Couden, RN, national program director for Option Care’s Bleeding Disorders Program.
“Our findings show we can save payers, including Medicare, Medicaid, and managed care insurers, significant costs without negatively impacting annual bleed rates.”
For this study, Couden and her colleagues conducted a retrospective analysis using dispensing data records from Option Care spanning the period from July 2015 through December 2015. The team compared these data to aggregate specialty pharmacy records from November 2013 through March 2014, which were analyzed in a previous study.2
In both data sets, patients receiving any FVIII product for prophylactic therapy were included. Patients being treated episodically or for immune tolerance induction were excluded, as were patients with extremely abnormal weights (40% below the 5th percentile or 40% above the 95th percentile based on weight-for-age charts from the US Centers for Disease Control and Prevention).
The researchers calculated a patient’s weekly dose of FVIII by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight. Patients with an overall mean weekly dose greater than 2 standard deviations from the mean were excluded.
There were 77 home infusion patients and 520 specialty pharmacy patients.
The home infusion patients had a mean FVIII dose of 102 units/kg/week, compared to a mean of 108 units/kg/week for the specialty pharmacy patients.
This difference translates to savings of $21,166 per patient per year among the home infusion patients.
Couden and her colleagues could not compare the ABR between the 2 data sets because the ABR was not measured in the specialty pharmacy patients. However, they said the ABR in the home infusion patients was favorable when compared to ABRs in published studies.
The mean ABR for the home infusion patients was 1.70. And, according to a recent review of research on hemophilia treatment strategies, mean ABRs range from 2 to 5 for intensive treatment protocols.3
ORLANDO—It may be possible for hemophilia patients to receive less factor VIII (FVIII) without increasing their risk of bleeding, according to a study presented at the World Federation of Hemophilia 2016 World Congress.
The study1 showed that hemophilia A patients who received prophylactic FVIII from the home infusion provider Option Care received 6 fewer units of FVIII per week than patients receiving prophylactic FVIII from specialty pharmacies.
This translated to a cost savings of more than $20,000 per patient each year.
The home infusion patients also had a lower annual bleed rate (ABR) than what is typically observed with intensive prophylaxis protocols in hemophilia, according to previous studies.
“By working with prescribers to closely monitor bleeds and collaborate on clinically appropriate optimization of treatment dose, Option Care’s utilization of factor VIII is less than the average with excellent outcomes,” said Joan Couden, RN, national program director for Option Care’s Bleeding Disorders Program.
“Our findings show we can save payers, including Medicare, Medicaid, and managed care insurers, significant costs without negatively impacting annual bleed rates.”
For this study, Couden and her colleagues conducted a retrospective analysis using dispensing data records from Option Care spanning the period from July 2015 through December 2015. The team compared these data to aggregate specialty pharmacy records from November 2013 through March 2014, which were analyzed in a previous study.2
In both data sets, patients receiving any FVIII product for prophylactic therapy were included. Patients being treated episodically or for immune tolerance induction were excluded, as were patients with extremely abnormal weights (40% below the 5th percentile or 40% above the 95th percentile based on weight-for-age charts from the US Centers for Disease Control and Prevention).
The researchers calculated a patient’s weekly dose of FVIII by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight. Patients with an overall mean weekly dose greater than 2 standard deviations from the mean were excluded.
There were 77 home infusion patients and 520 specialty pharmacy patients.
The home infusion patients had a mean FVIII dose of 102 units/kg/week, compared to a mean of 108 units/kg/week for the specialty pharmacy patients.
This difference translates to savings of $21,166 per patient per year among the home infusion patients.
Couden and her colleagues could not compare the ABR between the 2 data sets because the ABR was not measured in the specialty pharmacy patients. However, they said the ABR in the home infusion patients was favorable when compared to ABRs in published studies.
The mean ABR for the home infusion patients was 1.70. And, according to a recent review of research on hemophilia treatment strategies, mean ABRs range from 2 to 5 for intensive treatment protocols.3
ORLANDO—It may be possible for hemophilia patients to receive less factor VIII (FVIII) without increasing their risk of bleeding, according to a study presented at the World Federation of Hemophilia 2016 World Congress.
The study1 showed that hemophilia A patients who received prophylactic FVIII from the home infusion provider Option Care received 6 fewer units of FVIII per week than patients receiving prophylactic FVIII from specialty pharmacies.
This translated to a cost savings of more than $20,000 per patient each year.
The home infusion patients also had a lower annual bleed rate (ABR) than what is typically observed with intensive prophylaxis protocols in hemophilia, according to previous studies.
“By working with prescribers to closely monitor bleeds and collaborate on clinically appropriate optimization of treatment dose, Option Care’s utilization of factor VIII is less than the average with excellent outcomes,” said Joan Couden, RN, national program director for Option Care’s Bleeding Disorders Program.
“Our findings show we can save payers, including Medicare, Medicaid, and managed care insurers, significant costs without negatively impacting annual bleed rates.”
For this study, Couden and her colleagues conducted a retrospective analysis using dispensing data records from Option Care spanning the period from July 2015 through December 2015. The team compared these data to aggregate specialty pharmacy records from November 2013 through March 2014, which were analyzed in a previous study.2
In both data sets, patients receiving any FVIII product for prophylactic therapy were included. Patients being treated episodically or for immune tolerance induction were excluded, as were patients with extremely abnormal weights (40% below the 5th percentile or 40% above the 95th percentile based on weight-for-age charts from the US Centers for Disease Control and Prevention).
The researchers calculated a patient’s weekly dose of FVIII by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight. Patients with an overall mean weekly dose greater than 2 standard deviations from the mean were excluded.
There were 77 home infusion patients and 520 specialty pharmacy patients.
The home infusion patients had a mean FVIII dose of 102 units/kg/week, compared to a mean of 108 units/kg/week for the specialty pharmacy patients.
This difference translates to savings of $21,166 per patient per year among the home infusion patients.
Couden and her colleagues could not compare the ABR between the 2 data sets because the ABR was not measured in the specialty pharmacy patients. However, they said the ABR in the home infusion patients was favorable when compared to ABRs in published studies.
The mean ABR for the home infusion patients was 1.70. And, according to a recent review of research on hemophilia treatment strategies, mean ABRs range from 2 to 5 for intensive treatment protocols.3
Therapy seems safe, effective in kids with hemophilia
Photo courtesy of Baxalta
ORLANDO—Results of a phase 3 study suggest the full-length recombinant factor VIII therapy Adynovate (BAX 855) can be safe and effective as twice-weekly prophylaxis and to control bleeding in children with hemophilia A.
None of the patients in this study developed inhibitory antibodies, and there were no product-related adverse events.
The median annualized bleeding rate (ABR) was 2.0, and nearly 40% of patients did not have any bleeding episodes.
These results were presented at the World Federation of Hemophilia 2016 World Congress.* The study was funded by Baxalta, now part of Shire.
The study enrolled previously treated children younger than 12 years of age with no history of factor VIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
There were 66 evaluable patients with a median age of 6 (range, 1-11). Overall, 4,467,796 IU of Adynovate were infused. The mean number of exposure days was 53.98 per patient.
Safety
There was no indication of persistent binding antibodies against factor VIII, and none of the patients developed antibodies to host cell (Chinese hamster ovary) proteins.
There were 156 adverse events in 43 patients (65.2%), but none were considered related to Adynovate.
There were 4 unrelated serious adverse events in 3 patients—febrile neutropenia, pancytopenia, acute gastritis, and abdominal pain.
Efficacy
Patients received a median dose of 51.3 IU/kg per prophylactic infusion at a median frequency of 1.9 infusions per week.
Ninety-one percent of patients did not require dose adjustments. Reasons for dose adjustment included factor VIII trough levels less than 1%, increased risk of bleeding, and bleeding episodes.
Thirty-eight percent of patients did not experience bleeding events, 73% did not experience hemarthroses, and 67% did not experience spontaneous bleeding events.
The mean ABR was 3.0, and the median was 2.0. The mean joint ABR was 1.1, and the median was 0. The mean spontaneous ABR was 1.2, and the median was 0. The mean interval between bleeding episodes was 2.4 months.
There were a total of 70 bleeding episodes in 34 patients. All of these episodes were minor or moderate. Ninety-one percent of treated bleeding events were treated with 1 or 2 infusions. And 90% of bleeding events received treatment ratings of “excellent” or “good.”
Photo courtesy of Baxalta
ORLANDO—Results of a phase 3 study suggest the full-length recombinant factor VIII therapy Adynovate (BAX 855) can be safe and effective as twice-weekly prophylaxis and to control bleeding in children with hemophilia A.
None of the patients in this study developed inhibitory antibodies, and there were no product-related adverse events.
The median annualized bleeding rate (ABR) was 2.0, and nearly 40% of patients did not have any bleeding episodes.
These results were presented at the World Federation of Hemophilia 2016 World Congress.* The study was funded by Baxalta, now part of Shire.
The study enrolled previously treated children younger than 12 years of age with no history of factor VIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
There were 66 evaluable patients with a median age of 6 (range, 1-11). Overall, 4,467,796 IU of Adynovate were infused. The mean number of exposure days was 53.98 per patient.
Safety
There was no indication of persistent binding antibodies against factor VIII, and none of the patients developed antibodies to host cell (Chinese hamster ovary) proteins.
There were 156 adverse events in 43 patients (65.2%), but none were considered related to Adynovate.
There were 4 unrelated serious adverse events in 3 patients—febrile neutropenia, pancytopenia, acute gastritis, and abdominal pain.
Efficacy
Patients received a median dose of 51.3 IU/kg per prophylactic infusion at a median frequency of 1.9 infusions per week.
Ninety-one percent of patients did not require dose adjustments. Reasons for dose adjustment included factor VIII trough levels less than 1%, increased risk of bleeding, and bleeding episodes.
Thirty-eight percent of patients did not experience bleeding events, 73% did not experience hemarthroses, and 67% did not experience spontaneous bleeding events.
The mean ABR was 3.0, and the median was 2.0. The mean joint ABR was 1.1, and the median was 0. The mean spontaneous ABR was 1.2, and the median was 0. The mean interval between bleeding episodes was 2.4 months.
There were a total of 70 bleeding episodes in 34 patients. All of these episodes were minor or moderate. Ninety-one percent of treated bleeding events were treated with 1 or 2 infusions. And 90% of bleeding events received treatment ratings of “excellent” or “good.”
Photo courtesy of Baxalta
ORLANDO—Results of a phase 3 study suggest the full-length recombinant factor VIII therapy Adynovate (BAX 855) can be safe and effective as twice-weekly prophylaxis and to control bleeding in children with hemophilia A.
None of the patients in this study developed inhibitory antibodies, and there were no product-related adverse events.
The median annualized bleeding rate (ABR) was 2.0, and nearly 40% of patients did not have any bleeding episodes.
These results were presented at the World Federation of Hemophilia 2016 World Congress.* The study was funded by Baxalta, now part of Shire.
The study enrolled previously treated children younger than 12 years of age with no history of factor VIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
There were 66 evaluable patients with a median age of 6 (range, 1-11). Overall, 4,467,796 IU of Adynovate were infused. The mean number of exposure days was 53.98 per patient.
Safety
There was no indication of persistent binding antibodies against factor VIII, and none of the patients developed antibodies to host cell (Chinese hamster ovary) proteins.
There were 156 adverse events in 43 patients (65.2%), but none were considered related to Adynovate.
There were 4 unrelated serious adverse events in 3 patients—febrile neutropenia, pancytopenia, acute gastritis, and abdominal pain.
Efficacy
Patients received a median dose of 51.3 IU/kg per prophylactic infusion at a median frequency of 1.9 infusions per week.
Ninety-one percent of patients did not require dose adjustments. Reasons for dose adjustment included factor VIII trough levels less than 1%, increased risk of bleeding, and bleeding episodes.
Thirty-eight percent of patients did not experience bleeding events, 73% did not experience hemarthroses, and 67% did not experience spontaneous bleeding events.
The mean ABR was 3.0, and the median was 2.0. The mean joint ABR was 1.1, and the median was 0. The mean spontaneous ABR was 1.2, and the median was 0. The mean interval between bleeding episodes was 2.4 months.
There were a total of 70 bleeding episodes in 34 patients. All of these episodes were minor or moderate. Ninety-one percent of treated bleeding events were treated with 1 or 2 infusions. And 90% of bleeding events received treatment ratings of “excellent” or “good.”
Hemophilia guideline recommends integrated care model
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
AT WFH 2016 WORLD CONGRESS
Key clinical point: An integrated care model is recommended as optimal for management of persons with hemophilia.
Major finding: The joint National Hemophilia Foundation/McMaster University guidelines have been accepted by the National Guideline Clearinghouse.
Data source: Evidence-based recommendations on models of care.
Disclosures: The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
