Transcript Expanding Therapeutic Options

Expanding Therapeutic Options
for Hemophilia A and B:
Results of Recent Clinical Trials
Holleh D. Husseinzadeh, MD
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
A REPORT FROM THE 65TH ANNUAL MEETING OF THE NATIONAL HEMOPHILIA FOUNDATION (NHF 2013)
AND THE 55TH ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY (ASH 2013)
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1
Pharmacokinetics and Safety of BAX 855
in Patients with Severe Hemophilia A

In this phase I study, the mean half-life of BAX 855,
a PEGylated recombinant factor VIII (FVIII) product,
was 1.4 to 1.5 times greater than that of octocog alfa.

Other pharmacokinetic parameters were similar to,
or better than, those of octocog alfa.

The mean peak thrombin concentration was elevated
above baseline for > 120 hours after a single infusion
of 60 IU/kg of BAX 855.

No adverse events were recorded, nor did any of the
patients develop FVIII inhibitors or experience
thrombotic or allergic events or significant changes
in their vital signs or lab values.
Bevan D et al. NHF 2013, Abstract CR40
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2
First Successful Gene-Transfer Therapy
for Patients with Severe Hemophilia B

Ten adults with severe hemophilia B received F9
gene-transfer therapy, using an adeno-associated
virus as a vector, and were followed for 0.5–3 years.

Of the four patients given low or intermediate doses,
baseline factor IX (FIX) levels remained between 1%
and 3%, resulting in prolonged intervals between
prophylactic factor infusions in one patient and
eliminating the need for prophylaxis in two others.

All six patients given high-dose therapy had
postinfusion baseline FIX levels > 3% and no longer
required factor prophylaxis.

Transaminitis was managed with oral prednisolone.
Reiss UM et al. NHF 2013, Abstract CR24
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3
Extending the Half-life of Recombinant
Factor VIII with Fc Fusion Technology

In the A-LONG study, 165 previously treated males
12 years and older with severe hemophilia A received
prophylactic or on-demand treatment with rFVIIIFc.

The annualized rate of bleeding episodes was 1.6 in
patients receiving individualized, pharmacokinetically
driven prophylaxis; 3.6 in those receiving weekly
prophylaxis; and 33.6 in those receiving episodic
treatment.

Administration of just one injection of rFVIIIFc
resolved 87.3% of bleeding episodes.

None of the patients developed inhibitors to rFVIIIFc,
and no unusual adverse events were observed.
Mahlangu J et al. NHF 2013, Abstract CR38
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4
Extending the Half-life of Recombinant
Factor IX with Fc Fusion Technology

In the B-LONG study, 123 previously treated males
12 years and older with severe hemophilia B received
prophylactic or on-demand treatment with rFIXFc.

Over one half the patients on pharmacokinetically
adjusted intervals between doses were able to be
maintained on a dosing interval of 14 days or longer.
The annualized rate of bleeding episodes was 1.4–3.0
in patients receiving prophylaxis, compared with 17.7
episodes in those receiving on-demand therapy.
A single dose of rFIXFc was sufficient to control
90.4% of bleeding episodes.



No patients developed inhibitors to rFIXFc.
Powell J et al. NHF 2013, Abstract CR39
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5
Prophylactic vs On-demand FEIBA NF
Therapy in Patients with Inhibitors
Prophylactic, recurrent administration of FEIBA NF
appeared to be as safe as on-demand therapy while
significantly reducing all types of bleeds by 72.5% in
36 patients with hemophilia A or B who had developed
inhibitors to factor replacement concentrates.
Antunes SV et al. NHF 2013, Abstract CR41
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6
Adherence of Patients with Hemophilia A
or B to Prophylactic Factor Infusions

In adults, lower adherence was associated with an
increased number of bleeding episodes requiring
infusion of replacement factors, as well as more days
of work or school missed due to bleeding episodes.

Increased adherence was associated with better
physical health in children but not in adults.

In pediatric patients, adherence was not significantly
associated with the number of bleeding episodes but
was significantly associated with infection at the
injection site, increased hospital stays for control of
bleeding episodes, and missed school or work days
due to bleeding.
Vietri J et al. NHF 2013, Abstract SPI56
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7
Obesity Linked to Decreased Adherence
to Prophylactic Factor Infusions

Data were analyzed from 10,814 males 6–79 years old
in the United States with hemophilia A or B.

Half the population was overweight or obese.

Obese patients were 20% less likely to use home
infusion than were those of normal weight.

The percentage of obese patients using self-infusion
(44%) declined after age 40 years, no matter what the
patient's severity of disease or prophylactic regimen.

The increased difficulty of performing venipuncture
due to excessive adiposity was thought to contribute
to the low rate of adherence and decline with age.
Ullman M et al. NHF 2013, Abstract OTM47
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8
Outcomes After Total Joint Replacement
Total joint
replacement
resulted in
improvements
in range of
motion and
decreased pain
among 28
patients with
hemophilia A
or B or other
bleeding
disorders.
Goto Y et al. NHF 2013, Abstract OTM51
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9
Outcomes After Insertion of an Arteriovenous Fistula (AVF) for Venous Access

Seventeen patients, including 2 with von Willebrand
disease, 12 with hemophilia A, and 3 with hemophilia
B, who had an AVF inserted for venous access were
followed for 1–15 years (mean, 5 years).

No patients had bleeding complications, AVF-related
infection, or difficulty achieving venous access for
administration of factor replacements.

Fifteen patients reported "excellent" results, with
continued fistula viability.

Four of the 17 patients (24%), however, reported
dissatisfaction with the appearance of the AVF.
Tapia C et al. NHF 2013, Abstract CR35
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10
Food Insecurity in Hemophilia Patients

The overall prevalence of food insecurity was 16.7%
among 42 children and adolescents with hemophilia,
which is similar to that of the national average.

Food insecurity was less prevalent among children
with mild or moderate disease (5.6%) than among
those with severe hemophilia (25.0%).

Children who tended to be at increased risk of food
insecurity were:
» Older, taller, or heavier than the other children;
» Had a higher body mass index (BMI); or
» Belonged to a minority.
Ziha S et al. NHF 2013, Abstract CR25
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