Improving the Care of Patients With Hereditary Angioedema: Maximizing Protection With Long-Term Prophylaxis

Chair, Aleena Banerji, MD, discusses hereditary angioedema in this CME/MOC/AAPA activity titled “Improving the Care of Patients With Hereditary Angioedema: Maximizing Protection With Long-Term Prophylaxis.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/46GRq2g. CME/MOC/AAPA credit will be available until October 15, 2026.

1. Improving the Care of Patients With
Hereditary Angioedema
Maximizing Protection With Long-Term Prophylaxis

f

Aleena Banerji, MD

Professor of Medicine

Clinical Director, MGH Allergy and Immunology Unit
Harvard Medical School

Boston, Massachusetts

Go online to access full CME/MOC/AAPA information, including faculty disclosures.

100-2025, PeerView

2. Our Goals for Today

Augment your knowledge of the unmet needs of
patients living with HAE and current challenges and
barriers related to long-term prophylaxis

Improve your understanding of novel and emerging
options for long-term prophylaxis

Equip you with strategies to educate patients with
HAE on the benefits of long-term prophylaxis and how
to manage any adverse events

Provide guidance on creating individualized treatment
plans for patients with HAE

Copyright © 2000-2025, PeerView

3. Optimal Approach to Treatment
and Burden of Disease for
Patients With HAE

2000-2025, PeerView

4. gioedema: Bradykinin vs Histamine

Bradykinin famine
Severity of swelling Greater Lesser
Duration of swelling Longer Shorter
Risk for fatal airway obstruction Appreciable Exceedingly low
Abdominal attacks Very common Rare
Response to antihistamines, Poor Excellent

corticosteroids, epinephrine
PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

5. What Is Hereditary Angioedema?''2

+ Debilitating and potentially life-threatening autosomal dominant disease
+ Caused by an inherited deficiency in C1 esterase inhibitor

Symptoms typically develop in childhood or young adulthood
Swelling of the airway
can cause asphyxiation
Gastrointestinal swelling can cause
nausea, vomiting, and diarrhea

Recurrent swelling of the face, tongue,
gs, and abdomen

Ifuntreated, up to 40% mortality rate
from asphyxiation

Attacks can be triggered by stress, trauma, infection, menstruation, estrogens, and ACE inhibitor use

iron R ia. Emor Mod Cin Ar, 2022 40:9-118. 2, Bus Pe Eng J Med. 2020982196118, PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

6. HAE Diagnosis and Classification’?

Test Range

Recurrent cutaneous swelling (eg, peripheral swelling of hands and feet)
ay ye y y C1-INH

Recurrent abdominal pain and line Me
ne chong | level, mgaL Normal 16-33
Symptoms last 2-5 days (persistent swelling for weeks is not consistent with HAE) Normal 268
Symptoms do NOT respond to antinistamines, corticosteroids or epinephrine A
ll i Le Fe Equivocal 4167
Abnormal_ <40
C4 Level, C1 Inhibitor Level, and C1 Inhibitor Function C4
Normal 12-38

level, mg/dL.

C1-INH level and C1-INH level normal but C1-INH level and

function <50% of normal function <50% of normal function normal
Low C4 Low C4 suggests
HAE-C1-INH Type 4 HAE-C1-INH Type 2 HAE-nl. IH

PeerView

1. Maurer Met al. Alergy. 2022:77:1961-1990.2. Busse PJ la. J Allergy On Immunol Pract 2021.9.192-190.

PeerView.com/SPC827 Copyright © 2000-2025, Peerview

7. HAE Diagnostic Criteria?

HAE-C1-INH
+ Required criteria

= History of recurrent angioedema without urticaria
or use of medication known to cause angioedema

— Low (<50% of normal) C1-INH antigenic or
functional level

Low C4 level (at baseline or during an attack)
+ Supportive criteria

Demonstration of a pathologic SERPING1
mutation

— Family history of recurrent angioedema
- Age of symptom onset <40 y

saine 40 maid or equivalent for at east 1 mo, o a interval expected to ciated
1. Maure M et a orgy, 2022.77-1961-1990. 2. Busse PJ etal J Allorgy Ci Immunol Pract 20219 132-160.

PeerView.com/SPC827

HAE-nI-C1-INH
+ Required criteria

= History of recurrent angioedema without urticaria
or use of medication known to cause angioedema

— Documented normal or near normal C4, C1-INH
antigen, and C1-INH function

— Demonstration of a mutation associated with the
disease OR a positive family history of recurrent

angioedema and lack of efficacy of high dose (4x
daily) antihistamine therapy“

+ Supportive criteria

= History of rapid and durable response to a
bradykinin-targeted medication and predominant
documented visible angioedema (or in patients
with predominant abdominal symptoms, evidence
of bowel wall edema documented by CT or MRI)

PeerView

Copyrigl

8. Plasma Kallikrein-Kininogen Pathway’

Trace FXIla or trace activity
in native FXII

Prekallikrein
EE m ————>

Kallikrein

1 Kaplan AP eta. J Allergy Ci Immunol. 2002:109-195-209. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

9. Role of C1 Inhibitor Protein!

Trace FXIla or trace activity
in native FXII

a.

Prekallikrein

xia —

Kallikrein

x Inhibited by C1-INH

1 Kaplan AP eta. YAlorgy Cin Immun. 2002: 109195200. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

10. HAE: Generation of Bradykinin!

Trace FXIla or trace activity
in native FXII

|

Eu——-Enp-— —
N 7

Prekallikrein

HMW
kininogen

Kallikrein

Bradykinin

Loss of C1-INH in HAE

B2 Receptor
Angioedema

1. Kaplan AP ta Ary Gin Immunol 2002:100195.200. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

11. Burden of Disease in Patients With

Hereditary Angioedema Is High!

Acute/chronic treatment
ED visits

Hospitalization

Direct medical
Indirec!

Work/school
Productivity of Attacks

Quality Treatment

1. BanesiA. Ann Alergy Asthma Inmunol.2013:111329:396. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

12. High Rates of Anxiety and Depression in Patients With HAE"

In a US survey of 445 patients with HAE

49.9% 24.0%
zs tra,
experienced died
Er a

+ Patients experienced anxiety and depression
between HAE altacks, as well as during them

— Patients do not know when an attack will
‘occur, or which part of the body it will involve

— Both are associated with the fear of
developing a potentially fatal laryngeal attack

1.BanarjiA. et a. Ann Allergy Asthme Immunol. 2020;124:800-607. 2. Bork K otal Allergy Asthma Cli Immuna. 021.170.

PeerView.com/SPC827

Mean HADS Score (SD)
canwaaarvecd

Mean HADS Scores According to HAE Attack
Frequency in Past 6 Months

88
(47)
64
(48)
43
(3.5)
25
(2.9)
Anxiety Depression
=Noattacks "213 attacks
PeerView

Copyright © 2000-2025, PeerView

13. HAE: Guideline-Based Care

The international WAO/EAACI guideline for ®—
the management of hereditary angioedema
~ the 2017 revision and update

ry Angioedema Due to C1 Inhibitor Deficiency

“4 Management of Children With
Hereditary Angioedema Due

Allergy = 2
PERS POSITION ARTIELEANDEUIDELINES Deu

International consensus on the
of pediatric patients with here
inhibitor deficiency

M Fat Marion Sage X Ba 1. Bon“,
AL Varga’ A tenth

Canadian hereditary angioedema guideline

Stephen Ds", cu Ba, ren Br. ques Huber, Am
Van Eve! An un" Jonatan Semen” Kara Ba Tere ©
Timothy Cig Mente Fara ay Long Bae Zu. ene Bon Fata Bor
sine McCue Meee” Man Chu Poor, Be Rac. Don Sa Garn Saa

doo", Marc

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

14. HAE Treatment: Three Goals

Acute Attacks
Resolve angioedema symptoms as quickly as possible during an attack

Long-Term Prophylaxis
Decrease the overall number and severity of angioedema attacks

Short-Term Prophylaxis
Reduce the likelihood of swelling in response to anticipated events
that are likely to precipitate an attack (eg, medical or dental procedures)

1. Orca al tory. 201287:147-187 PeerView

PeerView.com/SPC827 Copyright

15. Treatment Recommenda

+ Evidence demonstrates efficacy and safety of treatment of HAE attacks with
C1-INH concentrates, plasma kallikrein inhibitor, and bradykinin B2 receptor
antagonist

— FFP is often effective, but may exacerbate some attacks; caution is required

— Androgens and antifibrinolytics do not provide reliably effective treatment of
attacks

+ Epinephrine, corticosteroids, and antihistamines are not effective

+ All patients should have at least 2 doses of on-demand medication and treat as
early as recognized

1.Mauro Met al. ler. 2022:7: 1981-1990. 2. Busse P e el Alergy Cin Immunol Pract. 20219 132.150 PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

16. Prophylactic Treatment Recommendati

o Considerations for the Initiation of
All patients are candidates for long-term Long-Term Prophylaxis

prophylaxis

ical Factors

Disease burden and patient preference should
be taken into strong consideration

Disease Burden Factors
Quality of

A C1-inhibitor is recommended for first-line
treatment

— Prior to FDA approval of garadacimab,
lanadelumab, berotralstat, and donidalorsen

Treatment-Specific Factors

+ Suggest modification of long-term prophylaxis in Risk-benefit pro
terms of dosage and time interval to minimize oe,
burden of disease Patient preference

1. Maurer Metal. Alergy, 2022.77.1001.1990.2. Busse Pl J Alergy Ci Immuno! Prec. 2021.9:132:10 PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

17. PeerView.com/SPC827

d Decision-Making?

Improves patient understanding of treatment options
and importance of long-term prophylaxis

Patients have increased confidence in decisions

Patients are more knowledgeable about their condition
and can monitor themselves

PeerView

18. Engaging Patients in Shared Decision-Making‘

DISCOVER

Explore patient needs

ledge availability of option

DECIDE

CHE

1. Banoj A et a. J Asthma ARorgy. 2021,14:110-125.

PeerView.com/SPC827

DISCUSS
* Discuss alternatives

+ Ensure goal alignment

+ Develop informed preferences

ed decisions ba:
rate information

PeerView

Copyright © 2000-2025, PeerView

19. t Are Barriers to

+ Treatment access and availability

+ Route of administration/treatment
burden

+ Adherence and persistence
(eg, complex dosing schedules)

+ Safety and tolerability concerns

+ Impact on quality of life (eg, ongoing
anxiety about breakthrough attacks)

+ Health system barriers

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

20. uation Rates Are High:

PIONEER-HAE Registry

+ Initial prophylactic breakdown among 179 patients observed between
2021 and 2024

— 55% initiated kallikrein inhibitors
— 37% began C1-esterase inhibitors
-6% used androgens

- 2% used anti-fibrinolytic agents

- 46% discontinued their index prophylactic therapy within a median
of 12.1 months for a variety of clinical and nonclinical factors

{UH ea. J Alergy Gin Imunol. 2025.15 up ABZ PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

21. Overcoming Barriers: Communication Strategies’?

+ Emphasize LTP benefits: Reduces attack frequency/severity, prevents complications, and
normalizes daily life

+ Tailor to fears: Highlight real-world data showing sustained QOL improvements

+ Address concerns transparently: “Most LTP therapies are well-tolerated; common effects
like injection-site reactions are mild and decrease over time”

— Maintain open communication
> Report new or bothersome symptoms promptly to the treating clinician
> Keep a symptom diary to track timing, severity, and potential triggers
— Adjust administration technique
> Rotate injection sites to minimize local reactions

> Use proper injection/infusion training and supportive measures (ice packs, topical
anesthetics, slower infusion rates if applicable)

1. in G tal. PLoS One. 202116 902608052. Anderson Jt aL Alergy Astana Cn Immunol 2021176. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

22. Overcoming Barriers: Communication S

+ Reassure with monitoring plans: “We'll check in frequently to manage any side effects”
= Regular follow-up visits and laboratory monitoring as recommended (eg, liver function, lipids,
injection-site reactions)
— Share updates on quality of life and tolerability at each visit
+ Supportive care for mild AEs
- Apply over-the-counter remedies when appropriate
- Stay well hydrated and maintain a healthy lifestyle to reduce fatigue or headache risks
+ Individualized treatment adjustments
- Discuss dose timing or regimen adjustments if AEs interfere with daily life
- Explore alternative prophylactic options if AEs persist or worsen
+ Emergency preparedness
- Ensure on-demand therapy is always available in case of breakthrough HAE attacks
— Have an action plan for serious or unexpected AEs (know when to call the clinic vs
seek urgent care)

1. sin G tal. PLOS One. 2021:1.00260905.2. Anderson Jt at Alergy Asma Cin Immunol. 2021176. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

23. Emerging Therapies for LTP in
Patients With HAE
How Can New Agents Aid Patients?

Copyright © 2000-2025, PeerView

24. Long-Term Prophylactic Options for HAE‘

Indi

Drug Name LOS Administration Approve ions Key Clinical Data

Plasma-derived SCG0IUKgtwice weekly Adults/children 26 years COMPACT: 84% attack reduction vs placebo

C1 esterase inhibitor CTINH FAs SAUL ea ara ERT
sean j ; 80 3: -50% attack reduction vs placebo:
ep! IV 1,000 1U twice weekly Adulsichilren 26 years Phase 3: "50%
APOX-2 Study: Up lo 44% attack reduction vs
Plasma kallikrein ‘ | Aduits/adolescents placebo; sustained efficacy at 48 weeks;
ences inhibitor Srl 150 no cay 212 years preferred for oral convenience but requires daily
dosing
HELP Study: 87% mean altack reduction vs
ey Plasma kalikrein SC.300 mg every Adulisichidren placebo
Er inhibitor 24 weeks 22 years SPRING Study: 94 8% attack reduction in
children 2-12 years
VANGUARD Study: 87% mean attack reduction
Garadacimab FXilainhibitor SC 200 mg every 4 wegks Aus ans" OLE: 94.2% reduction, 57.3% attack-ree over
12 years
a OASIS-HAE and OASISplus Studies:
81% attack reduction vs placebo (QW);
Donidalorsen oligonucleotide Sc 89 mg every 4-5 weeks Aduls/adolescenis 162% reduction in switch patients vs prior.
targeting 212 years a :
en prophylaxis; improved AE-Col. scores;
ES well-tolerated with mild injection-site reactions
À Mauer Mt Alor. 2027-1981-1900 2 Buse Pd oa. J Aloy Om Immunol Pract. 202181924 otal Aly. 20027787900. A
À MA ot at MEng YM 2028201211. 5. Craig Total Lancet 20234011078 9080, “wr PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

25. Reduction in Attack Rate With Berotralstat:

The Phase 3 APeX-2 Trial!

Study Design

Es
= = Placebo
— Placebo 8 u
+ 24 wk PE
Outcomes 2 5 Berotralstat
+ Berotralstal treatment reduced attack rate ER 110 mg
% at 110 mg and 45% at 150 mg E E Berotralstat
+ ' 150 mg
E
FDA approval pending for children aged <12 y 5
= a
En E Baseline 1 4 3 4 5 6
verse Events
Gastrointestinal, Study Drug Month

particularly early in treatment, but often
resolve with continued use

1.Zurow Beta. J Alergy Cn Immunol. 202%;148:164172.08. PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

26. Reduction in Attack Rate With Lanadelumab in Adults and

Adolescents: The Phase 3 HELP Trial!

Study Design

+ 125 patients with HAE aged 212 y
— Lanadelumab 150 mg Q4W SC
— Lanadelumab 300 mg Q4W SC
— Lanadelumab 300 mg Q2W SC
— Placebo

+ 26 wk

Outcomes

Imab treatment reduced
by ~85% at the
t dos
+ ~40% of the pa
lanadelumab were atta
during the study (vs 2.4%
receiving placebo)

Most Frequent Adverse Event
Mild injection-site reactions

1. Banoñj A ot al. JAMA. 2018:320-2108-2121.

PeerView.com/SPC827

Primary endpoint Secondary endpoint
A © Lanadelumab
25 150 mg Q4W
e (n= 28)
520
É 3 A Lanadelumab
A 300 mg Q4w
E qe (n=29)
2
Tgio HE Lanadelumab
5 $ 300 mg Q2W
Sos th H H it in=27)
N 4 É h opicero
0 (n=41)
Attacks Attacks © Moderate Attacks
From Requiring and Severe From
Days Acute Attacks Days
0-182 Treatment 14-182
PeerView

Copyright © 2000-2025, Peerview

27. Reduction in Attack Rate With Lanadelumab in Children:

The Phase 3 SPRING Trial!

Open-Label, Multicenter Study in Patients Aged 2 to <12 Years With HAE Type Mil
‘Treatment Period A Treatment Period B
Lanadelumab

150 mg

Observation:
(baseline HAE
attack rate)

Lanadelumab
150 mg Q4W

<12y
Lanadelumab
150 mg Q2W or €

Lanadelumab
150 mg Q2W

26 wi 26 wk

‘Over 52 Weeks of Treatment

Most common TEAE
Injection-site pain
patients (28.6% of patients)

No serious A No discontinuations
TEAES due to TEAES

762% 95%
® Patients Days

Lanadelumab Prevented Attacks

Decrease in mean attack
rate from baseline

sums 7 patients aged 6 lo <12 y switched
FH to aa after being attack-free for 26 wk

21 Patients Enrolled

20 <6 y (n= 4)

Y 20 patients completed study

Similar Systemic Exposure
in Both Age Groups

t

altack-free attack-free

int

Gto<12y{n= 17)

RER

© wean 184 atackso a baseline

Geometric mean (%CV) Cones
2 to <6 y: 24.6 (34) mogimL.
6 to <12 y: 332 (37.7) meghmL

Improvement in HRQOL

71.4% achieved clinically meaningful
improvement in PedsQL Total Score
from baseline to end-of study”

‘Patients aged 6 to <12y received 150 mg Q2W for 52 wk and had an option to switch to OSW in Period B ifthe patient was atlackre for 26 wk.

*An improvement of 24.5 (minimal cinicaly important diference) in the Peds OL. Tota Score,
1. Mautor Metal. J Allorgy On Immun. 2028; 12:201-211

PeerView.com/SPC827

PeerView

Copyright © 2000-2025, PeerView

28. Reduction in Attack Rate With Garadacimab:

The Phase 3 VANGUARD Study!

Study Design

+ 65 patients
+ 6mo

Percentage Reduction in the Hereditary
Angioedema Attack Rate per Month
‘Compared With the Run-In Period

250% "270% "90% =100% (atackimo)

Patients With Attack
Rate Reduction, %
o3BSSS8388E

Garadacimab
CEE)

1. Craig T et al. Lancet. 2028:401:1079.1090.

PeerView.com/SPC827

Time to First Hereditary Angioedema Attack
100

®
gr LoprankctstP<-0001
Es
$
In “Time to est here.
& Anglondema aci tor 75%
go of patients.
Le +s. inthe placebo group
3 2 Sida godemat
19 oop
$ Garocmab 200 mg Medlan time to est herectary
2»
: » + censored
Parano
REXTETEREITTTT
Time to First Hereditary Angioedema Attack
Since the Start of the Treatment Period, d
wann

‘Shaded areas represent 95% Ci. Patients wth no hereditary angioedema
‘attacks wore consored at study vist D182 or atthe and of nal vist

(whichever occured fs)

PeerView

Copyright © 2000-2025, PeerView

29. Donidalorsen—Reduction in Atta
Patient-Reported Outcomes: OASIS-HAE??

Change in AE-QoL Domain Scores
From Baseline to Week 24

ck Rates and Improved

ig
ge °
Change in the Rate of Hereditary EE Micon
'Angioedema Attacks Ed. me
23 ÉS more
É S LES
o 23. Poot pacto
i. 2
= Functloning FalgueMood Fearfihams _ Nutten
3 ‘AE-Qol. Domain
En ACET Total Score by Study Week
E00 : Denilson 20 mg SC AW
dE Donten 80m 8 AM
«125 88 0
Base 5 LE Pooled picaro
5
Time, wh gg ‘
Most Frequent Adverse Event o
Midi i D + 8 2 TE À
id injection-site reactions ‘Weck
Dra DOGC 45 4 EE 4
Donar 0 mp SC Om 2 2 2 2 2 m 2
Poole placebo 2 0 2 2 % 8 ®

2 P< 06. P<.01.<P < 001
1. Riedl MA eta. N Eng J Mod. 2024:391:21-31.2. Riedl MA etal. Alorgy.2025:90-2961-2968,

PeerView.com/SPC827

PeerView

Copyright © 2000-2025, PeerView

30. Assessing Disease Control in HAE‘?

+ Use validated tools: AAS, HAE-AS, AE-QoL
+ Criteria for suboptimal control

— 21 attack/month, significant QOL impact (eg, missed work/school), or breakthrough
attacks on current therapy

+ Consider comorbidities, lifestyle, and psychosocial burden in assessments

Assessment Application Advantages dvantag
Angioedema Activity Score Recurrent E a Brief Prospective nature
(AAS) angioedema Good internal consistency limits compliance
HAE Activity Score Allows for assessment of Requires accurate
(HAE-AS) HAE-CHANE 12 1moand6mo attack variability overtime _recall over 6 mo
‘Angioedema Quality of Live Recurrent in dr Sood eave Time-consuming
(AE-QoL) Questionnaire angioedema props Not HAE-specific

Good internal consistency

+ Schedule regular follow-ups (eg, every 3-6 months) to reassess control

1.80 Ket a. Alergy Ast Cl muna. 202117402 Andrea 8, Aya Pirin E Font Alergy. 2022. 3:945987 PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

31. Switching Patients With Suboptimal Disease Control: Key Points

Switch if current LTP fails to reduce attacks by >50% or improve QOL

Transition to therapies targeting different pathways

Monitor for 8-12 weeks post-switch; taper prior therapy gradually if needed

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

32. Patients With Subo

Switch in Treatment

Patients with HAE on prior LTPs Baseline
eee (swite

Tx)

î 7

Lanadelumab Berotralstat

E
“8

Baseline assessments
on prior LTPS

Acceptable

Week 16 of Donidalorsen Tx

Week 16

On Tx
80 mg donidalorsen Q4W

dis

&
“E

Tx assessments
on donidalorsen

Improved Preference
safety profile wee QOL Dites Lo | for donidalorsen
© 62% -10.4 “ja control? 84% of
Ne ° points> 93% patients
+ Part suche conan tom por TPs ung a predened suchng gr

* Based on Angioedema Qualty of Life questonnaire total score
« Percentage shown for patents who

reported welcontralld disease based on AFCT (score 210) at week 16.
1. Riedl MA eta. J Alorgy Cin immunol Pract. 2026:52219-2198(25}00500-9.

PeerView.com/SPC827

PeerView

Copyright © 2000-2025, PeerView

33. MOA Indication Phase

Drug Name
Antagonist of the
Deucrictibantt bradykinin B2 receptor; a 3 (CHAPTER-4)
orally administered eyes
e Plasma kallikrein inhibitor;
Navenibart? ‘subcutaneous Adults 3 (ALPHA-ORBIT)
NTLA-20023 Gene therapy Adults 3
siRNA duplex
ADX-324* oligonucleotide-targeting Adults 3
prekallikrein mRNA
1. Mis. cara ov/stud NCTORGTOB61.2. tosca goistusyiNCTO6842823. PeerView

3. ps incatals govietudyINCTO6534420, 4, hips /clniealtal gov/etudyINCTOS960213.

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

34. Case Presenta a 35-Year-Old Man

v Gary is a 35-year-old man with HAE who
reports 3-4 attacks a year for the past couple
of years

y” The swelling is usually in his hands and feet
after being at his construction job all day

v He has been using on-demand medication
and feels that it works well

v He presents today to review his plan of care
as he anticipates a job change with more
travel

How would you advise him?

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

35. Case Presentat

hn, a ear-Old Man

Y” John is a 54-year-old man who presents to your clinic with
a diagnosis of HAE with C1 inhibitor deficiency

v He has been prescribed icatibant to use on demand for
his HAE attacks

v This has been working well, but he notes an increase in
attacks recently ranging from 1 attack a month to
occasionally 2-3 attacks/month; his attacks always involve
his hands or feet

Y He would like to understand what are the best next steps
for treatment of his hereditary angioedema with C1
inhibitor deficiency

How would you advise him?

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

36. ar-Old Woman

Case Presentat Maria, a 2

+ Maria was diagnosed with HAE (C1-INH deficiency, type I)
at age 17; family history positive in mother and brother

+ Baseline disease course
- Before prophylaxis, she averaged 3-4 attacks/month,
often requiring on-demand C1-INH and missing school
or work
+ Current treatment
- On SC C1-INH twice weekly for the past 18 months
— Good initial response, but still averaging ~2
breakthrough attacks/month (abdominal pain and
extremity swelling)

— Finds administration burdensome: requires planning,
needle fatigue, and has had recurrent injection-site
discomfort

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, Peerview

37. Case Presenta

Impact on Daily Life

+ Maria works as a teacher; absences due to attacks have
created stress with her employer

+ Anxiety about unpredictable attacks, particularly during travel or
busy school days

+ Reports that her QOL has improved somewhat since starting
LTP, but she still feels “held back” by breakthrough attacks and
treatment burden

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

38. Case Presenta Ma

, a 29-Year-Old Woman (Cont'd)

Why is she a candidate for switching?

+ Suboptimal control: Despite adherence, still experiencing
frequent breakthrough attacks

+ Treatment burden: Regular SC injections are impacting
her lifestyle and leading to adherence fatigue

+ Desire for alternatives: Maria is interested in newer options that may offer more
sustained efficacy with less frequent administration

— Lanadelumab: Major attack-rate reduction and long attack-free periods;
SC injection every 2-4 weeks

- Berotralstat: Oral, convenient administration and is effective though
breakthrough attacks can occur

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

39. Case Presentat Maria, a 29-Year-Old Woman (Cont'd)

Maria decides to switch to donidalorsen

+ Dosing advantage: Administered SC once every 4-8
weeks, which may improve adherence and reduce
treatment burden and has shown success

Maria is initiated on donidalorsen 80 mg SC Q4W
+ After 6 months of stability, extended to Q8W dosing, maintaining control
+ Maria has a marked reduction in attack frequency: from ~2/month to $1 every 2-3 months
+ Several attack-free stretches of 12+ weeks; unprecedented for the patient

Decreased need for on-demand therapy (rare use of icatibant only once in the past 6 months)

No significant adverse effects; occasional mild injection-site erythema, self-resolving

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView

40. Case Presenta ‚a 29-Year-Old Woman (Cont'd)

Impact on Daily Life
+ Has not missed school days due to HAE since switching

+ Comfortable traveling without the stress of coordinating
frequent injections

+ Reports significantly reduced anxiety, improved sleep, and
greater sense of independence

+ Appreciates freedom from twice-weekly injections; 4-8-week dosing feels “much
more manageable”

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, Peerview

41. Summary and Key Takeaways

HAE carries a high burden
potentially life-threatening; high rates of anxiety, depression, and reduced quality of life

ine-based care
All patients should be considered for long-term prophylaxis
Continuous monitoring, QOL assessment, and open communication are critical

Patient-centered approach
+ Tailor therapy to patient life:

+ Address barriers such as administration burden, adherenc

+ Empower patients through tion, monitoring, and emergency

PeerView

PeerView.com/SPC827 Copyright © 2000-2025, PeerView