REIMAGINE
THE WAY YOU
TREAT HAE

HAE ATTACKS ARE UNPREDICTABLE

Hereditary angioedema (HAE) is a rare, autosomal dominant disease commonly associated with a deficiency or dysfunction of C1-esterase-inhibitor (C1-INH) activity. It causes spontaneous, recurrent, and potentially life-threatening swelling attacks in various regions of the body.2

The burden of HAE goes beyond the attack

Even after the physical symptoms of an attack subside, this lifelong disease has an ongoing effect on patients’ quality of life.3,4 Fear of the next attack can limit the way patients live their lives. Patients may avoid2,3*:

  • Educational and career opportunities3
  • Planning vacations3
  • Attending social engagements3
  • Participating in physical activities3

The 2021 HAE WAO/EAACI Guideline recommends evaluating patients with HAE type I or II for preventive treatment at every visit.5

*Based on qualitative (n=30) and quantitative (n=186) survey responses in the 2011 Hereditary Burden of Illness Study in Europe.3,6

RETHINK Prevention

TAKHZYRO is indicated for routine prevention of recurrent attacks of hereditary angioedema in patients aged 12 years and older.1

Help your patients prevent attacks with 1 subcutaneous self-injection every 2 weeks1

The recommended starting dose is TAKHZYRO 300 mg every 2 weeks. In patients who are stably attack free on treatment, a dose reduction of TAKHZYRO 300 mg every 4 weeks may be considered, especially in patients with low weight.1

The efficacy and safety of TAKHZYRO were evaluated in the HELP study and HELP open-label extension (OLE)1

HELP=Hereditary angioEdema Long-term Prophylaxis.

MEAN ATTACK REDUCTION WITH TAKHZYRO WAS CONSISTENT IN THE HELP STUDY AND HELP OLE1,7

HELP STUDY

87% relative reduction in attacks vs placebo at 6.5 months (P<0.001)1,8

  • LS mean monthly attack rate* (during treatment): 0.26 with TAKHZYRO (n=27); 1.97 with placebo (n=41) (primary endpoint)1
  • Mean monthly attack rate at baseline (during run-in period): 3.5 with TAKHZYRO; 4.0 with placebo8

Secondary endpoint: 83% relative reduction in the number of moderate or severe HAE attacks vs placebo at 6.5 months. LS mean monthly attack rate* (during treatment): 0.20 with TAKHZYRO (n=27); 1.22 with placebo (n=41). TAKHZYRO demonstrated statistical significance compared with placebo for all secondary efficacy endpoints in the HELP study (P<0.001).1,8

All results were with TAKHZYRO 300 mg every 2 weeks.

*LS mean monthly attack rate: investigator-confirmed attacks/4 weeks.1,8
HELP=Hereditary angioEdema Long-term Prophylaxis; LS=least squares.

HELP OLE

87% reduction in attacks vs baseline† at an average of 2.5 years1,7

  • Change in mean monthly attack rate with TAKHZYRO (N=209) during the HELP OLE treatment period: 3.05 to 0.25 (secondary endpoint)1,7

Secondary endpoint: 84% reduction in the number of moderate or severe HAE attacks vs baseline† at an average of 2.5 years. Change in mean monthly attack rate with TAKHZYRO (N=209) during the HELP OLE treatment period: 2.03 to 0.20.7

All results were with TAKHZYRO 300 mg every 2 weeks.

†For rollover patients, the baseline attack rate was calculated as the number of investigator-confirmed HAE attacks during the run-in period of the HELP study. For nonrollover patients, the baseline attack rate was calculated as the number of HAE attacks during the historical reporting period of the last 3 months, divided by the number of days they contributed to these periods, multiplied by 28 days.7
HELP=Hereditary angioEdema Long-term Prophylaxis; OLE=open-label extension.

ZERO ATTACKS FOR MONTHS AT A TIME1,7

IN THE HELP OLE

More than 8 OUT OF 10 PATIENTS HAD ZERO ATTACKS for ≥6 months7

HELP STUDY

  • Over the entire 6.5-month study (Day 0-182), 44% of patients taking TAKHZYRO (n=27) had zero attacks vs 2% of patients taking placebo (n=41) (prespecified exploratory endpoint)1,8
  • After 6 doses, 77% of patients taking TAKHZYRO (n=26) had zero attacks for 4 months vs 3% of patients taking placebo (n=37) (Day 70-182; anticipated time to reach steady-state concentration is ~70 days) (post hoc sensitivity analysis)1,8

HELP OLE

  • Over an average of 2.5 years, 82% of patients taking TAKHZYRO (N=209) had zero attacks for ≥6 months (prespecified exploratory endpoint)7

All results were with TAKHZYRO 300 mg every 2 weeks.

‡These findings are exploratory or post hoc in nature and therefore require further investigation to corroborate.
HELP=Hereditary angioEdema Long-term Prophylaxis; OLE=open-label extension.

IN THE HELP OLE

Patients had zero attacks on average for nearly 15 months§ (415 days, mean [SD] of 14.8 [12.4] months) in the HELP OLE (N=209; prespecified exploratory endpoint).1,7¶

All results were with TAKHZYRO 300 mg every 2 weeks.

§One month was defined as 28 days.9

These findings are exploratory or post hoc in nature and therefore require further investigation to corroborate.
HELP=Hereditary angioEdema Long-term Prophylaxis; OLE=open-label extension.

GET TO KNOW THE HELP OLE

Watch this video to learn more about the long-term safety and efficacy of TAKHZYRO from Dr Susan Waserman

HELP=Hereditary angioEdema Long-term Prophylaxis; OLE=open-label extension.

A FIRST-OF-ITS-KIND PREVENTIVE TREATMENT FOR HAE1

As a fully human monoclonal antibody, TAKHZYRO offers1*:

Targeted inhibition of plasma kallikrein, a critical regulator of HAE attacks1

*TAKHZYRO is produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology.1
cHMWK=cleaved high molecular weight kininogen.
HMWK=high molecular weight kininogen.

Watch TAKHZYRO in action

Use this video to help explain to your patients how TAKHZYRO works in the body

Redefine Dosing and Administration

  • Image of a stopwatch.

    1 SUBCUTANEOUS SELF-INJECTION1

  • Image of a marked calendar.

    EVERY 2 WEEKS1

  • Image of a silhouette with injection sites highlighted

    3 CHOICES FOR INJECTION SITE Abdomen, upper outer arms, or thighs1

HAE PREVENTION, READY TO USE1

The first and only preventive treatment for HAE available as a ready-to-use solution in either a prefilled syringe or a single vial for injection1,9,10

One recommended dose for all patients aged 12 years and older1

  • The recommended starting dose for TAKHZYRO is 300 mg every 2 weeks1
  • In patients who are stably attack free on treatment, a dose reduction of 300 mg every 4 weeks may be considered, especially in patients with low weight1

TAKHZYRO may be self-administered or administered by a caregiver only after training on subcutaneous injection technique by a healthcare professional.1

This medicinal product should only be taken if prescribed. Treatment should be initiated under the supervision of a physician experienced in the management of patients with HAE.1

REIMAGINE QUALITY OF LIFE

Significant improvement in quality of life with TAKHZYRO in the HELP study (tertiary endpoint)1,11*

As shown on the Angioedema Quality of Life Questionnaire (AE-QoL), which measures the patient-reported impact of angioedema over a 4-week recall period across 4 domains, patients taking TAKHZYRO in the HELP study reported clinically meaningful improvement (reduction of ≥6) across all domains.1,12

Mean change in total AE-QoL score†: -21.3 with TAKHZYRO (n=26; P<0.05); -4.7 with placebo (n=38) (tertiary endpoint).11*

IN THE HELP STUDY

81% of patients experienced clinically meaningful improvement1

  • Of patients taking TAKHZYRO, 81% experienced clinically meaningful improvement in quality of life vs 37% of patients taking placebo at 6.5 months (P<0.05)1,8,11

All patients, including those taking placebo, were permitted on-demand treatment for attacks.8

All results were with TAKHZYRO 300 mg every 2 weeks.
A reduction in score shows improvement.1
In the HELP study, patient quality of life was also assessed using the EuroQol 5-Dimension 5-Level Measure (EQ-5D-5L) tool.11

*These findings are tertiary endpoint analyses and therefore require further investigation to corroborate.

†LS mean change from baseline at 6.5 months.1,8
HELP=Hereditary angioEdema Long-term Prophylaxis; LS=least squares; OLE=open-label extension.

Clinically meaningful improvement in quality of life with TAKHZYRO in the HELP OLE (tertiary endpoint)7‡

Rollover patients from the HELP study experienced further quality-of-life improvement in the HELP OLE7

All results were with TAKHZYRO 300 mg every 2 weeks.
In the HELP OLE, patient quality of life was also assessed using the following tools: the EuroQol 5-Dimension 5-Level Measure (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI-GH), the Hospital Anxiety and Depression Scale (HADS), and the 12-Item Short-Form Survey (SF-12).13

‡These findings are tertiary endpoint analyses and therefore require further investigation to corroborate.

§LS mean change from baseline at 6.5 months in the HELP study. Mean change from Day 0 to the end of study in the HELP OLE.1,7
AE-QoL=Angioedema Quality of Life Questionnaire; HELP=Hereditary angioEdema Long-term Prophylaxis; LS=least squares; OLE=open-label extension; q2w=every 2 weeks.

Clinically meaningful improvement in quality of life across all domains with TAKHZYRO in the HELP OLE (tertiary endpoint)

Rollover patients from the HELP study experienced further quality-of-life improvement across all domains in the HELP OLE7,11,12

All results were with TAKHZYRO 300 mg every 2 weeks.
A reduction in score shows improvement.1

These findings are tertiary endpoint analyses and therefore require further investigation to corroborate.

#LS mean change from baseline at 6.5 months in the HELP study. Mean change from Day 0 to the end of study in the HELP OLE.1,7
AE-QoL=Angioedema Quality of Life Questionnaire; HELP=Hereditary angioEdema Long-term Prophylaxis; LS=least squares; OLE=open-label extension; q2w=every 2 weeks.

LONG-TERM SAFETY AND TOLERABILITY

Safety of TAKHZYRO was consistent in the HELP study and HELP OLE7

All results were with TAKHZYRO 300 mg every 2 weeks unless otherwise stated.

*The patient had a history of metabolic syndrome and fatty liver and used multiple concomitant suspect medications. The patient withdrew due to isolated, asymptomatic, and transient elevation of alanine transaminase (140 U/L) and aspartate transaminase (143 U/L) classified as related and severe on Day 139.14
HELP=Hereditary angioEdema Long-term Prophylaxis; OLE=open-label extension.

Additional safety information

Please consult the TAKHZYRO Summary of Product Characteristics (SmPC) before prescribing.

Guidance for use

TAKHZYRO treatment should be initiated under the supervision of a physician experienced in the management of patients with hereditary angioedema (HAE). TAKHZYRO may be self-administered or administered by a caregiver only after training on subcutaneous (SC) injection technique by a healthcare professional.

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated.

Warnings and Precautions

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated.

General: TAKHZYRO is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication. There are no available clinical data on the use of lanadelumab in HAE patients with normal C1-INH activity.

Interference with coagulation test: Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an interaction of lanadelumab with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by lanadelumab can increase aPTT in this assay. None of the increases in aPTT in patients treated with TAKHZYRO were associated with abnormal bleeding adverse events. There were no differences in international normalised ratio (INR) between treatment groups.

Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.

Interactions

No dedicated drug-drug interaction studies have been conducted. Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.

As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additive effect on lanadelumab-cHMWK response based on the mechanism of action (MOA) of lanadelumab and C1 esterase inhibitor

Immunogenicity

Treatment with lanadelumab has been associated with development of treatment emergent anti-drug antibodies (ADA) in 11.9% (10/84) of subjects. All antibody titres were low. The ADA response was transient in 20% (2/10) of ADA positive subjects. 2.4% (2/84) of lanadelumab-treated subjects tested positive for neutralising antibodies.

The development of ADA including neutralising antibodies against TAKHZYRO did not appear to adversely affect the pharmacokinetic (PK) and pharmacodynamics (PD) profiles or clinical response.

Adverse Reactions

The most commonly observed adverse reaction (52.4%) associated with TAKHZYRO was injection site reactions (ISR) including injection site pain, injection site erythema and injection site bruising. Of these ISRs, 97% were of mild intensity, 90% resolved within 1 day after onset with a median duration of 6 minutes.

Hypersensitivity reaction (mild and moderate pruritus, discomfort and tingling of tongue) was observed (1.2%)

Very common
(frequency ≥1/10):
Injection site reactions*
Common
(≥1/100 to <1/10):
Hypersensitivity**, dizziness, rash maculo-papular, myalgia, alanine aminotransferase increased, aspartate aminotransferase increased.

*Injection site reactions include: pain, erythema, bruising, discomfort, haematoma, haemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, oedema and rash.

**Hypersensitivity includes: pruritus, discomfort and tingling of tongue.

Suspected adverse reactions should be reported to Takeda at: GPSE@takeda.com.

Please see full EU Summary of Product Characteristics (SmPC).

References

1. Takhzyro. Summary of product characteristics. Takeda Pharmaceuticals International AG Ireland Branch; 2022. 2. Kaplan AP. Enzymatic pathways in the pathogenesis of hereditary angioedema: the role of C1 inhibitor therapy. J Allergy Clin Immunol. 2010;126(5):918-925. doi:10.1016/j.jaci.2010.08.012 3. Bygum A, Aygören-Pürsün E, Beusterien K, et al. Burden of illness in hereditary angioedema: a conceptual model. Acta Derm Venereol. 2015;95(6):706-710. doi:10.2340/00015555-2014 4. Bernstein JA. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am J Manag Care. 2018;24(suppl 14):S292-S298. 5. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2021 revision and update. World Allergy Organ J. 2022;15(3):100627. doi:10.1016/j.waojou.2022.100627 6. Caballero T, Aygören-Pürsün E, Bygum A, et al. The humanistic burden of hereditary angioedema: results from the Burden of Illness Study in Europe. Allergy Asthma Proc. 2014;35(1):47-53. doi:10.2500/aap.2013.34.3685 7. Banerji A, Bernstein JA, Johnston DT, et al; HELP OLE Investigators. Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE study. Allergy. 2022;77(3):979-990. doi:10.1111/all.15011 8. Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA. 2018;320(20):2108-2121. doi:10.1001/jama.2018.16773 9. Cinryze. Summary of product characteristics. Shire Services BVBA; 2022. 10. Berinert 3000 IU. Summary of product characteristics. CSL Behring GmbH; 2021. 11. Lumry WR, Settipane RA. Hereditary angioedema: epidemiology and burden of disease. Allergy Asthma Proc. 2020;41(suppl 1):S8-S13. doi:10.2500/aap.2020.41.200050 12. Weller K, Groffik A, Magerl M, et al. Development and construct validation of the angioedema quality of life questionnaire. Allergy. 2012;67(10):1289-1298. doi:10.1111/all.12007 13. Riedl MA, Bernstein JA, Craig T, et al. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy. 2017;7:36. doi:10.1186/s13601-017-0172-9 14. Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. Supplement 2. Supplementary online content. JAMA. 2018;320(20):2108-2121. Accessed March 1, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583584/bin/jama-320-2108-s002.pdf 15. Banerji A, Bernstein JA, Johnston DT, et al; HELP OLE Investigators. Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE study. Supporting information. Tables S1-S3. Allergy. 2022;77(3):979-990. Accessed March 1, 2022. https://onlinelibrary.wiley.com/doi/10.1111/all.15011 16. Cinryze. Prescribing information. Takeda Pharmaceuticals; 2021. 17. Craig T, Zuraw B, Longhurst H, et al. Long-term outcomes with subcutaneous C1-inhibitor replacement therapy for prevention of hereditary angioedema attacks. J Allergy Clin Immunol Pract. 2019;7(6):1793-1802.e2. doi:10.1016/j.jaip.2019.01.054 18. A long term safety study of BCX7353 in hereditary angioedema (APeX-S). ClinicalTrials.gov identifier: NCT03472040. Updated December 17, 2020. Accessed March 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03472040 19. Orladeyo. Prescribing information. BioCryst Pharmaceuticals, Inc; 2020. 20. Banerji A, Bernstein JA, Johnston DT, et al; HELP OLE Investigators. Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE study. Supporting information. Figure S1. Allergy. 2022;77(3):979-990. Accessed March 1, 2022. https://onlinelibrary.wiley.com/doi/10.1111/all.15011 21. Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. Supplement 1. Protocol and statistical analysis plan. JAMA. 2018;320(20):2108-2121. Accessed March 1, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583584/bin/jama-320-2108-s001.pdf