Important Safety Information Prescribing Information ALPROLIX Patient Site

Make ALPROLIX®
the choice for hemophilia B*

CHOOSE PROVEN PROTECTION
CHOOSE PROVEN PROTECTION

ALPROLIX delivered proven bleed protection and bleed control with median annualized spontaneous bleed rates (AsBRs) of ≤1 per year.

CHOOSE PERSONALIZED Dosing
CHOOSE PERSONALIZED Dosing

The recommended starting regimen is every 7 (at 50 IU/kg) or 10 (at 100 IU/kg) days with the potential to adjust to 14 days based on patient response.

CHOOSE Real-World Experience
CHOOSE Real-World Experience

ALPROLIX is the only extended half-life (EHL) therapy that has been prescribed for more than 1000 patients since its approval in 2014.‡§

* ALPROLIX may be appropriate for your patients.
ALPROLIX has been proven to help patients prevent bleeding episodes using a prophylaxis regimen.
These data represent post-marketing experience of ALPROLIX and are based on specialty pharmacy dispensing records, specialty distributor shipment records, 3PL shipments records, and internal retention estimates from May 2014 through July 2017.1
§ The FDA approval date of ALPROLIX was March 28, 2014.

Choose ALPROLIX® for extended efficacy


Median annualized spontaneous bleed rates were ≤1 per year

  • Evaluated the safety, efficacy, and pharmacokinetics of ALPROLIX up to 77 weeks in 123 previously treated males (≥100 exposure days) aged 12 to 71 years with severe hemophilia B (≤2 IU/dL endogenous factor IX)2
  • Consisted of a fixed-interval arm (n=63), a fixed-dose arm (n=29), an episodic (on-demand) arm (n=27), and a surgical arm (n=12)

Overall and on-demand median annualized bleed rates

  • Overall median annualized bleed rates for the fixed-interval prophylaxis arm (n=61)* were 3.0 (IQR: 1.0, 4.4) and 1.4 (IQR: 0.0, 3.4) in the fixed-dose prophylaxis arm (n=26)*
  • Median annualized bleed rates for on-demand treatment (n=27) were 11.8 (IQR: 2.6, 19.8) for spontaneous bleeds and 17.7 (IQR: 10.8, 23.2) for overall bleeds

*Adjustments to dose or interval were made to maintain FIX trough level 1%–3% above baseline or higher, as clinically indicated to prevent bleeding.

Over 90% of patients achieved bleed control with only 1 infusion

A total of 636 bleeding events were observed across the 3 arms of the study (fixed-interval prophylaxis, fixed-dose prophylaxis, and episodic).

  • Median total dose to treat a bleeding episode was 46.99 IU/kg (IQR: 33.33, 62.50)
  • Dose was selected by the investigator based on the severity of the bleed2

Choose ALPROLIX® for personalized prophylaxis dosing


ALPROLIX offers two starting regimens with different doses and intervals*

*Higher dose or more frequent dosing may be needed in patients under 12 years of age.


Extended dosing options may be possible for
appropriate patients based on their response

Offer your patients the potential to extend from 10-day dosing to a 14-day regimen, based on their response.2


More than half of study subjects in the fixed-dose arm adjusted
to a dosing interval of 14 days or more in B-LONG2

More than half of study subjects in the fixed-dose arm adjusted to a dosing interval of 14 days or more in B-LONG2

  • Overall median dosing interval on study was 12.5 days [IQR: 10.4, 13.4]
  • During last 6 months on study in subjects on study ≥9 months, median dosing interval was 13.8 days [IQR: 10.5, 14.0]
  • Subjects in the fixed-dose prophylaxis arm received 100 IU/kg fixed dose with the initial 10-day interval adjusted. Dosing interval of ≥14 days achieved for their last 3 months on study2

The ALPROLIX extended half-life is powered by Fc Fusion technology

ALPROLIX is believed to utilize the natural recycling pathway of IgG1 to stay in circulation longer.3

3-Step process to extend half-life of ALPROLIX

ALPROLIX binds to FcRn3

Fc region of ALPROLIX enables it to bind to the neonatal Fc receptor, FcRn.

FcRn delays ALPROLIX degradation3,4

FcRn is part of a naturally occurring pathway that diverts ALPROLIX away from the lysosome, delaying degradation.

ALPROLIX is cycled back into circulation, resulting in its prolonged plasma half-life3,4

The process delays degradation, but evidence from the Phase 3 B-LONG study has shown that Fc does not accumulate. Eventually, Fc degrades naturally into amino acids.4


ALPROLIX was the first recombinant extended half-life product approved for use in hemophilia B

ALPROLIX is a recombinant clotting factor IX genetically fused to the Fc region of IgG1

ALPROLIX is made in a human cell line that allows for post-translational modifications that are comparable to endogenous factor.5

Only ALPROLIX offers the potential for your patients to receive their recommended dose with just one vial6-12

Graphic is for illustrative purposes only.

ALPROLIX has the widest range of dosage strengths in hemophilia B, including a 4000-IU vial6-12

Choose ALPROLIX® for real-world experience

prescribed factor IX with an extended half-life1*

prescribed ALPROLIX since its approval in 20141†‡

units of ALPROLIX shipped across the country

* Based on approximately 18,200 pharmacy dispensing records from January 2016 through July 2017.1
Based on specialty pharmacy dispensing records, specialty distributor shipment records, 3PL shipments records, and internal retention estimates from May 2014 through July 2017.1
The FDA approval date of ALPROLIX was March 28, 2014.
§ Units include units that have been shipped to patients from May 2014 through September 2017 and do not include inventory at SPPs or SDs.1

A majority of HCPs and HTCs have prescribed ALPROLIX nationwide1 ||

HTCs prescribing ALPROLIX

HCPs=healthcare professionals; HTCs=hemophilia treatment centers.

|| Based on data from US pharmacy dispensing records for ALPROLIX as of August 2017.1                     

Choose ALPROLIX® for its established safety profile with low adverse reactions

The safety of ALPROLIX was evaluated in a Phase 3 clinical trial— B-LONG

B-LONG results confirmed zero inhibitors, vascular thrombosis events,
and anaphylaxis in previously treated patients.*

In B-LONG, previously treated patients had: *Post-marketing experience of ALPROLIX revealed:
Zero inhibitors detected Formation of inhibitors to factor IX has been reported following administration of ALPROLIX, including in previously untreated patients.
Monitor all patients regularly for the development of inhibitors by appropriate clinical observations and laboratory tests.
Zero vascular thrombosis events The use of factor IX products has been associated with the development of thromboembolic complications, especially in individuals receiving continuous infusion through a central venous catheter.
Zero anaphylaxis Hypersensitivity reactions have been reported with ALPROLIX. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with factor IX replacement products.
Data from the Phase 3 clinical trial of 123 previously treated patients followed for up to 77 weeks who transitioned from traditional factor IX products.

Reported adverse reactions while using ALPROLIX

The most common adverse reactions (incidence ≥1%) observed
in clinical trials were headache and oral paresthesia.

Obstructive uropathy was reported in 1 subject with hematuria who developed an obstructing clot in the urinary collecting system. The event resolved with hydration and the subject continued prophylactic treatment with ALPROLIX. A causal relationship of clot formation to ALPROLIX was not established.

The safety of ALPROLIX was evaluated in a Phase 3 clinical trial—B-LONG

The safety of ALPROLIX was evaluated up to 77 weeks in 123 previously treated males (≥100 exposure days) aged 12 to 71 years with severe hemophilia B (≤2 IU/dL endogenous factor IX). B-LONG consisted of a fixed-interval arm (n=63), a fixed-dose arm (n=29), an episodic (on-demand) arm (n=27), and a surgical arm (n=12).2

Indications and Important Safety Information

CONTRAINDICATIONS:

ALPROLIX is contraindicated in patients who have a known history of hypersensitivity reactions, including anaphylaxis, to the product or its excipients (sucrose, mannitol, sodium chloride, L-histidine and polysorbate 20).

WARNINGS AND PRECAUTIONS:

Hypersensitivity reactions have been reported with ALPROLIX. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with Factor IX replacement products. The presence of inhibitors has been associated with allergic reactions with Factor IX replacement therapies, including with ALPROLIX. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, hypotension, rash, nausea, vomiting, paresthesia, restlessness, wheezing and dyspnea. Discontinue use of ALPROLIX if hypersensitivity symptoms occur, and initiate appropriate treatment. Formation of neutralizing antibodies (inhibitors) to Factor IX has been reported following administration of ALPROLIX, including in previously untreated patients. Monitor all patients regularly for the development of inhibitors by appropriate clinical observations and laboratory tests. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Closely observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product. Individuals with Factor IX inhibitors may be at an increased risk of anaphylaxis upon subsequent challenge with ALPROLIX. The use of Factor IX products has been associated with the development of thromboembolic complications, especially in individuals receiving continuous infusion through a central venous catheter. ALPROLIX should be administered as bolus infusion over several minutes. The safety of ALPROLIX administration by continuous infusion has not been studied. To confirm adequate Factor IX levels have been achieved and maintained, monitor patient plasma Factor IX levels by performing a validated one-stage clotting assay. Factor IX results can be affected by the type of aPTT reagent used. Measurement with a one-stage clotting assay using a kaolin-based aPTT reagent has been shown to result in an underestimation of Factor IX levels. Monitor for the development of Factor IX inhibitors if the expected Factor IX levels in patient plasma are not attained, or if bleeding is not controlled with the recommended dose of ALPROLIX. Perform a Bethesda assay to determine if Factor IX inhibitors are present.

ADVERSE REACTIONS:

Common adverse reactions (incidence ≥1%) observed in clinical trials were headache, oral paresthesia, and obstructive uropathy.

INDICATIONS:

ALPROLIX® [Coagulation Factor IX (Recombinant), Fc Fusion Protein] is a recombinant DNA derived, coagulation Factor IX concentrate indicated in adults and children with hemophilia B for:

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

Limitation of Use
ALPROLIX is not indicated for induction of immune tolerance in patients with hemophilia B.

Please see Full Prescribing Information.

References:

1. Data on file, Bioverativ. 2. Powell JS, Pasi KJ, Ragni MV, et al; B-LONG Investigators. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369(24):2313-2323. 3. Shapiro A. Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia. Expert Opin Biol Ther. 2013;13(9):1287-1297. 4. Blumberg RS, Lencer WI. Antibodies in the breakdown lane. Nat Biotechnol. 2005;23(10):1232-1234. 5. McCue J, Osborne D, Dumont J, et al. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein. Haemophilia. 2014;20(4):e327-e335. 6. IDELVION® [package insert]. Marburg, Germany: CSL Behring GmbH; 2017. 7. AlphaNine® SD [package insert]. Los Angeles, CA: Grifols Biologicals Inc; 2013. 8. BeneFIX® [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc, a subsidiary of Pfizer Inc; 2015. 9. Ixinity® [package insert]. Berwyn, PA: Aptevo BioTherapeutics LLC; 2016. 10. Mononine® [package insert]. Kankakee, IL: CSL Behring LLC; 2016. 11. Profilnine® SD [package insert]. Los Angeles, CA: Grifols Biologicals Inc; 2010. 12. Rixubis® [package insert]. Westlake Village, CA: Baxalta US Inc; 2016.