First-in-class ALTUVIIIO:
XTEND-Kids pediatric study

PHARMACOKINETICS

Deliver ~3 days near normal for your pediatric patients

In children <12 years, ALTUVIIIO provided mean steady-state Factor VIII levels >40% for ~3 days and an unprecedented trough level of 10% at ~Day 71

PHASE 3 XTEND-KIDS FVIII ACTIVITY AFTER FIRST DOSE IN PK SUBGROUP2*

PK line graph showing that ALTUVIIIO maintains >40% Factor VIII activity levels for ~3 days in pediatric patients

END OF STUDY POPULATION (N=73)1

Once-weekly ALTUVIIIO delivered Factor VIII trough levels:

  • 10.9% in children <6 years
  • 16.5% in children 6 to <12 years

ALTUVIIIO offered a mean half-life of 40.2 hours in
children <12 years—the longest of any Factor VIII replacement therapy1,3-11‡

*
Data from this subgroup analysis includes 37 children (<12 years) receiving weekly IV infusion of 50 IU/kg ALTUVIIIO. PK parameters shown are based on plasma FVIII activity measured by the aPTT-based one-stage clotting assay.1
Mean steady-state trough levels were computed using available measurements at Week 52/end of study PK sampling visit for the pediatric population in the XTEND-Kids study (n=72).1
Comparison of data from XTEND-Kids with half-life data recorded in prescribing information of approved Factor VIII replacement therapies.aPTT=activated partial thromboplastin time; FVIII=Factor VIII; IU=international unit; IV=intravenous; PK=pharmacokinetics. 

Study design

XTEND-Kids clinical trial

A 52-week, multinational, multicenter, single-arm, open-label Phase 3 trial was conducted in previously treated patients <12 years with severe hemophilia A1,2

The XTEND-Kids study included 74 patients that were screened for 8 weeks and underwent prophylactic treatment for 52 weeks
§
A subject in the <6 age group who had a positive inhibitor result at baseline (pre-exposure to study drug) and was withdrawn after 3 exposure days was excluded.
||
A subject in the 6 to <12 age group who received an intense consolidation treatment (2 to 3 infusions per week) for 15 weeks, after 2 traumatic hip joint bleeds was excluded from the efficacy analysis as the subject did not receive the weekly prophylaxis treatment as specified in the protocol for an extended period.

Primary endpoint12

The occurrence of inhibitor development

Secondary endpoints12

ABR for treated bleeds by type and location

Pharmacokinetics

Safety and tolerability

Perioperative management

Treatment of bleeds

ABR=annualized bleed rate.

RESULTS

No Factor VIII inhibitors were detected during the XTEND-Kids study1,12¶

Primary Endpoint: INCIDENCE OF NEUTRALIZING ANTIBODIES TO FACTOR VIII

Antibody icon with 0.0% representing that no Factor VIII inhibitors were detected during the XTEND-Kids study

Formation of inhibitors to Factor VIII is possible following administration of ALTUVIIIO.1

Defined as an inhibitor result of ≥0.6 BU/mL and confirmed by a second test result from a separate sample drawn 2 to 4 weeks following the date of the original sample.12

BU=Bethesda unit; CI=confidence interval.

Effective bleed protection with a once-weekly infusion1

In the XTEND-Kids trial:

ALTUVIIIO DEMONSTRATED PROVEN BLEED PROTECTION
IN CHILDREN <12 YEARS (N=72)#

0.0 and 0.6 icons showing Median and Mean bleed protection, respectively, in XTEND-Kids study
#
Based on treated bleeds.

CI=confidence interval; Q1=25th percentile; Q3=75th percentile.

Most patients experienced zero bleeds when treated with ALTUVIIIO prophylaxis1

In the XTEND-Kids trial**:

63.9%, 87.5%, 83.3% dials showing the percent of patients that had 0 bleeds (overall, spontaneous, joint) during XTEND-Kids
**
Based on treated bleeds.

Effective on-demand bleed management with only 1 infusion1,12

Visual demonstrating that 95.3% of bleeds were resolved with 1 infusion in the XTEND-Kids study
††
Percentage based on the number of treated bleeding episodes in the sensitivity analysis set, which excluded two patients.1,12

Excellent perioperative response across XTEND-1 and XTEND-Kids1

The hemostatic response of ALTUVIIIO was deemed “Excellent/Good‡‡” by the investigator surgeon in:

100% dial showing the percent of excellent/good hemostatic responses around surgery during all ALTUVIIIO trials
‡‡
Hemostatic response during major surgery was assessed using the International Society on Thrombosis and Haemostasis (ISTH) 4-point response scale: excellent, good, moderate, or poor/none. Based on pooled data from XTEND-1 and XTEND-Kids.1
§§
Defined as any surgical procedure, either elective or emergent, that usually involves general anesthesia and/or respiratory assistance, in which a major body cavity is penetrated and exposed, or a substantial impairment of physical or physiological functions is produced. Major surgeries include major orthopedic procedures such as arthroplastics; joint replacements of the knee, hip, and elbow; joint revisions; and ankle fusions. Other major surgeries include molar-tooth extractions, dental restoration and tooth extraction, circumcision, and rhinoplasty/mentoplasty.1,12
||||
Median preoperative dose per surgery was 50 IU/kg (range: 12.7-61.9).1

Safety

ALTUVIIIO: Demonstrated safety profile in XTEND-Kids trial1

ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its components.

No Factor VIII inhibitors were detected

All patients were monitored for neutralizing antibodies (inhibitors) to Factor VIII in the clinical programs

  • No patients developed neutralizing antibodies to Factor VIII
  • Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests

Hypersensitivity reactions

  • No adverse allergic-type hypersensitivity reactions, including anaphylaxis, were reported
  • Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with ALTUVIIIO

Adverse reactions observed

ADVERSE REACTIONS WITH FREQUENCY OF
>10% REPORTED FOR ALTUVIIIO1

Adverse Reactions

Percentage of Patients (n) (N=74)

Pyrexia

12.2% (9)

Simple dosing with ALTUVIIIO

Infused the same way as other Factor VIII replacement therapies but taken less frequently.

LEARN MORE ABOUT DOSING

INDICATION

ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is a von Willebrand Factor (VWF) independent recombinant DNA-derived, Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:

  • Routine prophylaxis to reduce the frequency of bleeding episodes
  • On-demand treatment & control of bleeding episodes
  • Perioperative management of bleeding

Limitation of Use

ALTUVIIIO is not indicated for the treatment of von Willebrand disease.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.

WARNINGS AND PRECAUTIONS

  • Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with ALTUVIIIO. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Advise patients to discontinue use of ALTUVIIIO if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.
  • Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
  • If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient's ALTUVIIIO Factor VIII activity level.

ADVERSE REACTIONS

The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.

INDICATION

ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is a von Willebrand Factor (VWF) independent recombinant DNA-derived, Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:

  • Routine prophylaxis to reduce the frequency of bleeding episodes
  • On-demand treatment & control of bleeding episodes
  • Perioperative management of bleeding

Limitation of Use

ALTUVIIIO is not indicated for the treatment of von Willebrand disease.

IMPORTANT SAFETY INFORMATION

ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.

WARNINGS AND PRECAUTIONS

  • Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with ALTUVIIIO. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Advise patients to discontinue use of ALTUVIIIO if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.
  • Formation of neutralizing antibodies (inhibitors) to Factor VIII is possible following administration of ALTUVIIIO. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
  • If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient's ALTUVIIIO Factor VIII activity level.

ADVERSE REACTIONS

The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.

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aPTT=activated partial thromboplastin time; PK=pharmacokinetics.