EAHAD 2023 Congress Review

EAHAD 2023 Congress Review 

Thinking Differently in Haemophilia: 

Gene therapy at EAHAD 2023 

Welcome to the EAHAD 2023 Congress Review. 

The 16th Annual EAHAD Hybrid Congress took place 

online and in Manchester, UK. 

This review contains a selection of abstracts and 

presentations from the scientific sessions – with a focus 

on GT for haemophilia. Our picks include key efficacy 

updates from GENER8-1, HOPE-B, and BENEGENE-2. 

In addition, we look at real-world considerations as 

GT moves into everyday practice, managing common 

AEs and steroid use, plus an update on the WFH registry 

project that will enhance our understanding of long-term 

durability and safety of GT for people with haemophilia. 

I hope you enjoy our summary of the key data. 

Professor Cedric Hermans 

MORE INSIDE: 

Patient perspectives page 12 

Wider considerations for GT page 15 

Non-Factor products in development page 19 

Assays for GT page 21 

Clinical data for GT 

in haemophilia A 

A round-up of the 

latest efficacy data 

for ROCTAVIAN ® 

(valoctocogene roxaparvovec).* 

Read more on page 3 

Clinical data for GT 

in haemophilia B 

Results for etranocogene 

dezaparvovec, fidanacogene 

elaparvovec, and AMT-060. 

Turn to page 4 

GT safety updates 

AE reports and follow-up 

across GT for haemophilia. 

Find out more on page 8 

The speaker, oral and poster 

abstracts can be found here 

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals 

are asked to report any suspected adverse reactions. 

*Not yet licensed in the EU. Treatments mentioned in this document may not be approved for use in your country. Please consult local licensing 

authorities for further information. Some links in this document are “external links” to websites over which BioMarin has no control and for which 

BioMarin assumes no responsibility. When visitors choose to follow a link to any external website, they are subject to the cookie, privacy and legal 

policies of the external website. Compliance with applicable data protection and accessibility requirements of external websites linked to from this 

website falls outside the control of BioMarin and is the explicit responsibility of the external website. 

HaemDifferently.expert is organised and funded by BioMarin. For healthcare professionals only. 

This medicine received a conditional marketing authorisation. The latest API can be found on 

the HaemDifferently.expert website, under the Prescribing Information tab. Or click here. 

© 2023 BioMarin International Ltd. All Rights Reserved. EU-ROC-00487 May 2023 

1


Current Status of GT in Haemophilia 

The treatment of haemophilia has evolved, driven by a need for better 

protection from bleeding. But have GT advances outpaced our fundamental 

knowledge of AAV gene transfer in humans? 

Radek Kazmarek from the Indiana University 

School of Medicine, US, gave a presentation 

on the current status of GT in haemophilia. 

Early GT studies reported low-level 

expression in muscle, and only short-lived 

expression in the liver – accompanied by 

transaminitis. The presenter stated that 

subsequent work has enabled a molecular 

revolution in the treatment of haemophilia, 

with AAV liver-targeted GT products now 

approved for use. However, Dr Kazmarek 

noted that some concerns remain about 

durability, predictability, and safety of GT 

for haemophilia. He went on to explain that 

at least 17 genes have been found to be 

associated with FVIII or VWF plasma levels, 

which could explain some of the variability 

observed. Suboptimal therapeutic responses 

cannot be adjusted, due to the universal 

development of anti-AAV antibodies, which 

precludes repeat GT dosing. At the other end 

of the spectrum, extremely high Factor levels 

after GT can result in treatment-induced 

haemophilic thrombosis. With regards 

immunotoxicity, some targets for mitigation 

have been suggested, these include IL-1, 

IL-6, the IL-6 receptor, type 1 IFN, and mTOR. 

In the future, there could also be a role for 

biochemical modulators to enhance rAAV 

transduction. Some unique challenges face 

GT for haemophilia A, including the fact that 

FVIII is primarily produced in LSECs, not 

hepatocytes, and that FVIII is a large and 

complex glycoprotein, which tends to misfold. 

Work on biobetter FVIII variants, engineered 

protein, or oversized AAV vectors may 

address some of these issues. Alternative 

gene transfer systems are also being 

investigated, such as lentiviral vectors or dual 

AAV/LNP gene editing. To help support robust 

scientific inquiry for the next generation of 

GT for haemophilia, a framework of known 

and unknown outcomes has been published. 

In his conclusion, Dr Kazmarek gave his 

opinion that AAV GT is still a work in progress, 

with plenty still to learn. 

Latest Clinical Data in GT for Haemophilia A 

Up-to-date results from a post hoc analysis of GENER8-1 – an ongoing 

Phase 3 trial of valoctocogene roxaparvovec in severe haemophilia A. 

A presentation by Doris Quon from the 

Orthopaedic HTC in Los Angeles, US, 

shared results from a post hoc analysis 

examining endogenous FVIII activity and 

procedure-related FVIII use and bleeding in 

the GENER8-1 trial. This looked at 134 male 

participants aged 18 or older and with 

FVIII ≤1 IU/dL on prophylaxis (ITT population) 

who received 6x10 13 vg/kg valoctocogene 

roxaparvovec. Endogenous FVIII activity 

was assessed throughout using CSA, and 

the closest measurement to a procedure 

or bleed was identified. Procedures were 

identified as non-invasive (e.g. tattoo, dental 

Mean FVIII activity and number of procedures performed 

Mean FVIII activity (IU/dL per CSA) 

150 

100 

50 

0 

n=67 n=33 n=11 

Minor 

without FVIII 

cleaning) or invasive (e.g. joint debridement, 

biopsies). FVIII prophylaxis could be used 

perioperatively, but major procedures were 

performed with FVIII treatment regardless 

of participant Factor level. Investigators 

were asked what had influenced their 

decision to perform procedures without FVIII. 

By the 2-year data cut, 260 procedures 

had been performed in 77 men. Dr Quon 

highlighted that of 111 invasive procedures, 

44 required FVIII treatment and 67 did not. 

Of the 44 performed with FVIII, 11 were 

major (joint debridement, arthrodesis) and 

33 were minor (dental extraction, biopsies). 

Minor invasive procedures performed without FVIII treatment were 

associated with higher participant FVIII activity per CSA 

Minor 

with FVIII 

Major 

with FVIII 

Number of procedures 

45 

40 

35 

30 

25 

20 

15 

10 

5 

0 

n=4 

n=6 

n=3 


The 67 procedures performed without FVIII 

use were all minor. In the ITT population, 

mean FVIII activity at Weeks 52 and 104 

was 42.4 and 22.7 IU/dL, respectively. At the 

closest measurement to minor procedures, 

mean endogenous FVIII was 16.2 IU/dL for 

participants who required FVIII treatment, 

and 50.5 IU/dL for those who did not. 

The 6 participants who underwent major 

procedures all received FVIII infusions 

regardless of endogenous activity, and 

required more units than those undergoing 

minor procedures – 255.4 versus 67.2 IU/kg, 

respectively. Relatively few invasive 

procedure-related bleeds occurred, 

with just 18 episodes in 14 participants; 

13 episodes required FVIII treatment and 

5 did not; mean FVIII activity at the time was 

60.4 and 10.4 IU/dL for those not requiring 

and requiring treatment, respectively. 

The presenter noted that investigator 

questionnaire responses reflected the 

nature of personalised medicine with 

valoctocogene roxaparvovec, showing 

that most investigators had undertaken 

a case-by-case discussion about the use 

of FVIII treatment for procedures, given 

the participant’s endogenous activity 

achieved with GT and the type of procedure. 

The presentation concluded that FVIII use 

around minor procedures was associated 

with lower participant endogenous activity. 

Dr Quon closed by saying that the data from 

this study and the opinions reflected in the 

questionnaire suggest that valoctocogene 

roxaparvovec provides effective haemostatic 

control for up to 2 years, even with FVIII 

activity below WFH guidelines. [OR09] 

Latest Clinical Data in GT for Haemophilia B 

A selection of results for etranocogene dezaparvovec, fidanacogene 

elaparvovec, and AMT-060 in people with haemophilia B. 

Since GT for haemophilia is an innovative 

treatment approach, little is known about the 

management of surgery afterwards. An oral 

presentation from Niamh O’Connell from 

St James’s Hospital in Dublin, Ireland, looked 

at the management of dental procedures and 

surgeries in men who received etranacogene 

dezaparvovec in the Phase 2b (n=3) and 

Phase 3 (n=54) clinical trials. Information was 

collected about on-study dental procedures 

and surgeries, as well as exogenous FIX 

prophylaxis used to manage these events. 

At 2- and 3-years post-dosing, mean 

one-stage FIX activity levels were sustained 

at Over 2-year = 36.7 (n=50) Over 3-year = 

36.9 (n=3). The presenter reported that to 

date, 58% of participants have undergone 

a total of 18 dental procedures and 40 

surgeries; 45% were minor, and 

55% major. Joint surgeries comprised 

just over half of major surgeries (55%). 

No exogenous FIX prophylaxis was used 

for perioperative management of 72% dental 

procedures, including tooth extraction and 

implantation. Prophylaxis was also not used 

for perioperative management of 61% of 

minor and 9% of major surgeries. Either 

standard half-life or extended half-life 

FIX products were used in the remaining 

procedures; only a single FIX dose was used 

for 80% of dental procedures and 86% of 

minor surgeries. No safety concerns were 

raised, no inhibitors developed, and no 

thrombotic events were reported. In the 

abstract associated with this presentation, 

the authors concluded that etranacogene 

dezaparvovec achieved sustained FIX activity 

levels sufficient to undergo dental procedures 

and minor surgeries without exogenous FIX. 

The management of surgeries after GT was 

as expected, and comparable to people with 

mild haemophilia B, and there were no new 

safety concerns. [OR10] 

A poster from Pipe et al. looked at the 

durability of bleeding protection and FIX 

activity in people with and without AAV5 NAb 

in the Phase 3 HOPE-B trial, in which 54 adult 

males received etranacogene dezaparvovec 

at a dose of 2x10 13 gc/kg. AAV5 NAbs on 

day of dosing showed 33 were NAb-negative, 

and 21 were NAb-positive. The median 

AAV5 NAb titre in NAb-positive participants 

Summary of FIX activity* (%) by baseline AAV5 NAb status (Full analysis set) 

was 56.9, but 95% of NAb-positive participants 

had titres less than 1:700. One participant 

(titre 3212) did not express FIX Padua, and 

one (titre 198.9) received a partial dose; the 

other 52 participants were able to discontinue 

FIX prophylaxis. The poster showed that at 

18- and 24-months post-dose, no correlation 

was identified between baseline NAb titre 

and FIX level up to titre


between infusion-related reactions and 

baseline NAb status (p=0.0956). The authors 

concluded that etranacogene dezaparvovec 

provided significant ABR reductions and 

an acceptable AE profile, regardless of 

NAb status, through 24-month follow-up. 

There was no association between baseline 

NAb status (titre


13.3% resumed prophylaxis; 5 due to low 

FIX activity, and 1 due to bleed frequency. 

Mean FIX activity was 27.5 at Month 15, 

measured by OSA, and remained relatively 

stable at Month 24. Turning to look at the 

safety profile, Dr Kavakli noted that during the 

study, 84.4% of participants experienced ≥1 AE, 

and 62.2% received ≥1 dose of corticosteroid 

for elevated ALT, with mean time to initiation of 

GT: Safety 

45.3 days, and mean duration of 107.5 days. 

There was no thrombosis, malignancy, or 

inhibitor development. In summing up, 

Dr Kavakli concluded that treatment with 

fidanacogene elaparvovec met the primary 

endpoint, yielding endogenous FIX expression, 

resulting in significant decreases in bleeding 

and infusion rate, and with a generally well 

tolerated safety profile. 

Key safety questions for GT include transaminitis and corticosteroid use, 

and geno- or phenotoxicity. These presentations looked at key safety data 

from ongoing clinical trials, as well as some practical considerations. 

Wolfgang Miesbach gave a presentation on 

monitoring and dealing with AEs associated 

with GT. He began by stating that the most 

frequent AE seen with GT is ALT elevation, but 

there are also effects on immunosuppression, 

systemic infusion-related AEs, and the 

potential for highly elevated transgene 

and thrombosis. Possible risks debated 

include coagulopathy when additional Factor 

concentrates or emicizumab are given, or the 

development of inhibitors – although none 

have been reported to date. Other concerns 

include the risk of immune reactions to 

pre-existing AAV antibodies, and long-term 

malignancy and unexpected events. In clinical 

development, infusion-related AEs were 

documented in most trials, and were seen 

during therapy or up to 48 hours later. 

Phase 3 studies reported infusion-related 

AEs in 13% of haemophilia B subjects, and 

37% of haemophilia A. These AEs include 

mild events such as pyrexia, tachycardia, 

and hypotension, with only rare reports 

of severe hypotension and anaphylactic 

reactions. But there are effective strategies to 

deal with these, including slowing or pausing 

the initial infusion, providing supportive 

care, and extending the observation 

period. With regard to ALT elevations, 

Professor Miesbach noted that the first 

description of this AE in haemophilia GT 

was in 2006, when transient elevations were 

associated with a gradual decline in Factor 

expression, and a CD8+ T cell response 

against the AAV capsid. Subsequently it 

has been established that prednisolone is 

effective in limiting hepatocellular toxicity, 

as well as preserving transgene expression, 

especially when initiated early. Data from 

long-term 8-year follow-up show no recurrent 

episodes of elevated ALT, and no persistent 

or late-onset AEs. A dose-finding trial on 

the prophylactic use of immunosuppressives 

examined three different strategies in 

patients undergoing GT for haemophilia B. 

The results showed that different prophylactic 

regimens could not prevent ALT elevation, 

and were associated with late transaminitis 

when immunosuppression was tapered. 

It is possible that different management is 

needed for variable ALT patterns, taking into 

account timing of first elevation, and peak 

levels – which feasibly could have different 

underlying causes. Turning to rarer events, 

Professor Miesbach outlined the few cases 

of deep vein thrombosis and arteriovenous 

fistula thrombosis seen in haemophilia GT 

trials. He also noted there have been 4 cases 

of malignancy after GT for haemophilia, 

but histopathological findings suggest no 

evidence of integration of vector genomes, 

and concluded these cases are unrelated to 

GT. Long-term canine models suggest no 

altered liver function, no liver toxicity, and 

no evidence for tumorigenesis, but a small 

proportion of vectors do integrate, so there 

remains a potential risk. In neurological 

indications for AAV-based treatment safety 

alerts include toxicity in the spinal ganglia, 

muscular atrophy, and X-linked myotubular 

Summary of AEs in AAV-based GT 

lmmunogenicity 

Hepatotoxicity 

lmmunosuppression 

related AE 

Relevance for gene therapy of haemophilia 

• Pre-existing neutralising anti-AAV 

antibodies 

• Infusion-related reactions by innate 

immune response 

• T cell response against transduced cells 

ALT elevation: 

• transient 

• non-pathogenic 

• but related to transgene decrease 

• Dependent on the number, duration 

and effects of ALT elevation 

myopathy, but the mechanism for these 

is not well understood. Safety guidance 

recommends that HCPs promptly assess 

patients with worsening liver function tests 

or signs or symptoms of acute liver illness; 

if patients do not respond adequately to 

corticosteroids, consult a hepatologist and 

consider adjustment of the steroid regimen. 

A hub-and-spoke model has been proposed 

to manage GT in clinical practice, which 

encourages collaboration with hepatologists, 

psychologists, and physiotherapists. The 

model allows HTCs to become better qualified 

to deliver GT, to distribute responsibilities, 

and to make this treatment option accessible 

to all people with haemophilia. An important 

role for HTCs will be evaluation of factors such 

as liver health prior to GT, and to monitor 

and manage AEs post infusion. In conclusion, 

Professor Miesbach outlined that patient 

information, patient selection, and cooperation 

within the hub-and-spoke model will be key 

elements for patient safety, and this may 

evolve with more long-term data, including 

lifelong data collection in registries and 

safety surveillance systems. 

Relevance for other gene therapies 

• Complement activation and 

inflammation in non haemophilia trials 

leading to thrombotic microangiopathy 

• Progressive cholestatic hepatitis 

leading to acute liver failure 

• Dependent on the number, duration 

and effects of ALT elevation 

Professor Wolfgang Miesbach 

8 9


Astermark et al. analysed elevated ALT in the 

HOPE-B trial – a principal safety outcome. 

The poster explained that ALT elevations were 

defined per protocol as ALT more than twice 

the subject’s baseline or greater than the 

laboratory upper limit of normal. Overall, 

12 ALT elevations were reported in 11 subjects; 

6 events were classed as mild, 5 as moderate, 

and 1 as severe. Baseline demographics in 

affected patients were comparable to those 

without ALT elevation. The poster highlighted 

that mean time to first elevation was 46.5 days, 

and mean elevated ALT duration was 38.2 days. 

Corticosteroids were given in 9 subjects per 

protocol, without reported serious AEs, and 

the mean corticosteroid use duration was 

79.8 days, at a mean dose of 27.2 mg/day. All 

subjects discontinued corticosteroids between 

Days 85–170 after GT. Mean FIX (% normal) in 

9 subjects treated with corticosteroids peaked 

at 22.2, prior to starting steroid treatment, and 

was 17.9 a fortnight afterwards. In comparison, 

mean FIX in those without increased ALT 

Effect of ALT elevations on FIX activity in HOPE-B 

Mean (±SD) peak FIX activity prior 

to corticosteroid treatment 

Mean (±SD) FIX activity prior to 

corticosteroid treatment 

Mean (±SD) FIX activity 2 weeks 

post-corticosteroid treatment 

Mean (±SD) FIX level post-etranacogene 

dezaparvovec administration 

Participants who received 

corticosteroids, n=9 

were 43.5, 46.0, 42.0, and 41.7 at 6, 12, 18, 

and 24-months post-treatment, respectively. 

Furthermore, mean ABR at Months 7–24 

was 0.8 and 1.1 in subjects with and without 

elevated ALT, respectively, and no subject 

returned to continuous prophylaxis. The 

authors concluded that these results suggest 

the supportive care and corticosteroid protocol 

used in HOPE-B achieved normalisation of 

liver transaminase levels and maintenance 

of most pre-steroid levels of FIX, without 

needing a return to prophylaxis. [PO040] 

Rasko et al. showcased the safety and 

efficacy of GT for haemophilia in HIV-positive 

participants. In the poster the authors note that 

people living with HIV represent an important 

subset within the haemophilia A community, 

but concerns about the interaction of AAV 

vectors with HIV medications – and associated 

hepatotoxicity – have led to their exclusion 

in many GT trials. This analysis evaluated 

SPK-8011 and SPK-8016 GT in 4 HIV-positive 

Participants with ALT 

elevations, n=11* 

Participants without 

ALT elevations, n=42 

22.2 (10.5) – – 

17.1 (8.1) – – 

17.9 (10.6) – – 

6 months 18.7 (11.1) 21.6 (11.8) 43.5 (17.6) 

12 months 16.7 (9.7) 20.3 (11.5) 46.0 (20.1) 

18 months 15.6 (7.9) 18.1 (9.1) 42.0 (21.2) 

24 months 15.5 (7.7) 18.4 (9.6) 41.7 (18.0) 

*One participant had an alcohol-related transaminase elevation that occurred on study day 740, 

and therefore was excluded from this analysis. 

Astermark et al [PO040] 

participants identified from two clinical trials 

and long-term follow-up studies. Individual 

safety and efficacy outcomes were assessed 

alongside concomitant HAART regimens. 

Each participant also had a history of 

treated HCV with a negative viral load. 

Only 1 serious AE was reported, which was 

considered unrelated to SPK-8011/8016. 

Overall, 8 treatment-related AEs were reported 

over median follow-up of 3.48 years; 7 were 

related to immunomodulatory therapy, and 

1 moderate ALT increase was related to GT. 

Of the 4 people with comorbid HIV, 75% had 

no indication of immune response to the 

vector, and did not receive immunomodulation, 

in comparison to 12.5% of the 24 participants 

without HIV. Prednisone was required in 

1 participant for a presumed capsid immune 

response; the authors noted that attempts 

to taper were confounded by intermittent 

elevated ALT and positive ELIspot tests 

for T-cell IFN-γ activity. To manage this, 

the HAART was optimised to facilitate the 

use of tacrolimus, but despite this trough 

levels were initially supratherapeutic due 

to a drug–drug interaction, requiring a 

further regimen change. Over 2.9–4.9 years, 

participants sustained FVIII expression levels 

of 15.1–28.0% as measured by OSA. Following 

infusion, ABR was reduced by 98.3–100% for 

all bleeds, and by 99.2–100% for spontaneous 

bleeds; AIR was reduced by 98.3–100%. 

The poster conclusions suggest these findings 

point to similar efficacy and safety profiles 

for SPK-8011 and SPK-8016 in HIV-positive 

participants compared to previous reports 

from the overall study populations. The data 

suggest carefully selected concomitant HAART 

is possible alongside liver-directed AAV GT, 

but the authors highlight that expertise in 

HIV management is essential and should be 

sought when immunomodulatory therapy is 

required. The final point on the poster states 

that these preliminary results encourage 

future AAV GT studies that do not exclude 

people living with HIV. [PO162] 

Rasko et al. also presented a poster on 

patterns of joint bleeds following GT with 

fidanacogene elaparvovec. Overall, 15 people 

with haemophilia B were treated at a dose 

of 5e11 vg/kg in a Phase 1/2a study for 

52 weeks, and 14 enrolled in long-term 

follow-up for up to 5 years. As of August 2022, 

8 patients were continuing, 4 completed, and 

2 discontinued, representing 3–6 years post 

infusion. The poster showed that FIX activity 

generally remained in the mild to normal 

range post infusion, and ABRs were low, with 

annual means


GT: Real-World Data 

Real-world registries are an effective way to pool enough data to enable 

robust evaluation of rare safety events. GT registries will also collect 

information on durability. 

In an oral presentation, Donna Coffin 

from the WFH discussed building a global 

resource for the long-term follow-up of GT in 

haemophilia, and a collaboration between the 

WFH and national registries. The presenter 

outlined the core features of WFH GTR – 

a prospective, observational, and longitudinal 

registry based on a core data set that was 

developed by the GTR Steering Committee. 

Data will be collected either directly from 

participating HTC or through transfer from 

existing national registries via an integration 

programme. Participating HTCs will invite 

patients to enrol in the GTR once they have 

made the decision to receive GT, in a clinical 

trial or otherwise. Once informed consent is 

obtained, baseline and historic information 

will be obtained, and prospective data will 

be collected on an ongoing basis, at infusion 

and follow-up site. The GTR is already 

collaborating with national bodies in the 

USA, Germany, Netherlands, and Canada. 

Discussions on potential integrations with 

other national registries are ongoing. [OR07] 

process, infusion day, and follow-up. 

Along the journey, they have been identified 

as being key for psychosocial support, and 

actively participate to continuous education of 

patient conditions and treatment. Conversely, 

it has been highlighted that they may 

themselves require education about GT 

to help patients considering this option, 

and to support throughout the journey 

Patient journey for haemophilia including GT, and the role of the nurse 

1 

18 YEARS OF AGE 

Diagnosis 

2 

in a well-informed and safe manner. 

A multidisciplinary perspective, including 

nurse perspectives for mapping a patient 

journey for haemophilia, is key to improve 

quality of care, especially in case of paradigm 

shifts such as GT. The authors argues that this 

work places the nurse as one of key actors 

in management of people with haemophilia 

who may consider receiving GT. [PO305] 

Prophylactic Treatment 

• Realize on-demand/ 

prophylactic infusions 

• Teach parents, how to infuse 

their child, and then the child 

to self-infuse 

• Ensure psychosocial support and 

motivate for adherence to treatment 

3 

Aware of Gene Therapy (GT) 

• Repeat neutral information 

about treatment opportunities 

including gene therapy to 

empower patient, including 

using the teach-back method 

Patient Perspectives 

Understanding patient perspectives and the individual’s GT journey is key to 

improve quality of care as this game-changing option moves into the mainstream. 

4 

Consider Gene Therapy 

5 

Eligibility Assessment 

• May coordinate eligibility 

testings 

• Communicate with other 

Haemophilia treatment 

centre members 

6 

Shared-decision Making Process 

• Checks if patient has all 

information needed to take 

a decision 

• First point of contact in case 

of questions/concerns 

• Provides information and 

psychosocial support 

LeQuellec et al. looked at the patient journey 

for people with haemophilia, with a focus 

on nurse perspectives and roles. The poster 

showed how a patient journey for haemophilia 

including GT was mapped, using a mixed 

system-approach including ethnographical 

interviews of patients, family members 

and HCPs – plus nurses with experience in 

haemophilia care with or without experience 

in GT clinical trials. Market research, literature 

screening, and peer-to-peer discussions 

were used to identify the critical steps, the 

people involved, and their respective roles 

in each step. Based on insights from 38 people 

interviewed and additional secondary sources, 

12 steps were identified from diagnosis to 

long-term follow-up post-administration of GT. 

These steps include 7 GT-specific items such 

as eligibility assessment, shared-decision 

making process, informed consent obtention 

as well as patient’s commitment to shortand 

long-term monitoring. As part of the 

multidisciplinary team, nurses were identified 

as playing a major role in two-thirds of 

steps, including but not limited to raising 

awareness about GT, shared decision-making 

7–8 

11 

Final Go & Inform Decision 

Short-term Monitoring 

• Track changes in QoL and 

need for care 

• Support patients in case of 

questions or concerns 

• Monitor the patient, manage 

bleeds or ALT elevations in the first 

months after GT administration 

9 

12 

Pre-infusion 

• Reassures patient that they 

made the right decision in 

case of doubts 

• Backs up or refers to gene 

therapy centre in case of questions 

Long-term Follow-up 

• Track changes in QoL and 

need for care 

• Support patients in case of 

questions or concerns 

• Monitor the patient, manage 

bleeds 

10 

Gene Therapy Infusion Day 

• First point of contact in case 

of questions or concerns 

during infusion day 

• Supports medical procedures 

and monitors patient closely for 

4 hours after GT 

Haemophilia 

nurse 

or 

Gene therapy 

nurse 

LeQuellec et al [PO305] 

12 13


Woollacott et al. examined treatment 

preferences of people with haemophilia, 

showcasing the results from a discrete 

choice experiment in the UK. This study 

aimed to quantify patient preferences 

regarding treatment attributes when 

considering GT. 125 participants completed 

an online survey to collect demographic, 

clinical, and QoL information, before 

watching an educational video on GT 

principles. A discrete choice experiment was 

administered to elicit treatment preferences 

using five key attributes identified through 

prior qualitative research. Participants 

completed 14 hypothetical treatment 

scenarios (choice tasks) and relative weights 

were calculated. ‘Safety concerns’ for 

treatments were the most important attribute 

(33% importance), followed by ‘therapeutic 

option’ (how often treatment is provided; 

31%) and ‘role limitations’ (how haemophilia 

affects daily life; 24%). The least important 

attributes were ‘treatment effectiveness’ and 

‘hospital attendances and self-management’ 

(9% and 3%, respectively). This study showed 

that people with haemophilia in the UK 

consider the safety of novel treatments 

including GT as highly important in 

decision-making. Furthermore, therapeutic 

option and impact on role limitations are 

valued more importantly than effectiveness. 

The poster conclusions highlight that 

this relationship should help inform 

health technology assessment decisions 

regarding the value patients place on 

specific attributes of GT. [PO338] 

In a session showcasing EAHAD research 

grant reports and awards, Ilaria Cutica 

from the University of Milan, Italy, gave 

an oral presentation on KAHaGeT – 

examining the knowledge and attitudes of 

people with haemophilia toward GT. Previous 

studies in the UK and the Netherlands have 

found a general lack of knowledge and 

education, but Professor Cutica believes 

this is the first study to investigate patient 

attitudes toward GT, their information 

needs, priorities and concerns, and how 

these factors might impact willingness to 

accept GT. In total 80 haemophilia patients 

at one HTC in Italy completed an online 

questionnaire to assess clinical data, 

GT knowledge, willingness to accept GT, 

and information needed for decision-making 

as well as priorities for safety, effectiveness, 

and QoL improvement, main concerns, 

and psychological characteristics such 

as risk-taking attitude. Overall, 87% of 

participants had haemophilia A, 80% were 

classed as severe, and a history of inhibitors 

was reported in 15%. The vast majority (93%) 

were satisfied with their current treatment. 

Professor Cutica showed that patients 

typically had poor knowledge of GT – with a 

few exceptions such as around general aims 

and functioning, and main positive effects. 

Two-thirds of people were able to answer 

fewer than half the questions correctly, and 

knowledge of detailed functioning, eligibility 

criteria, and the possible long- and 

short-term consequences was poor. 

Professor Cutica went on to demonstrate 

that the most appealing benefit of GT is 

not needing to perform infusions, followed 

by a reduction in bleeding, and having 

fewer restrictions in sports or travelling. 

Conversely, the most frequent concern that 

patients have is about potential long-term 

treatment consequences such as cancer, 

followed by short-term side-effects such as 

liver inflammation, and the possibility that GT 

will not be effective. In regard to willingness 

to undergo GT, 51% of participants would not 

accept it even when suggested by doctors; 

one of the factors that most influenced this 

preference was the possibility of losing 

effectiveness over time. Among the factors 

that most influenced the willingness to 

undergo GT were the possibility of fewer 

restrictions in sports and travelling and feeling 

safer in high-risk situations, and the prospect 

GT: Wider Considerations 

of reduction in bleeding and chronic joint 

pain. Importantly, having higher knowledge 

of GT increased the rate of acceptance. 

When asked for a minimum desired level of 

Factor that would make GT attractive, most 

patients said 25% for at least 15 years. These 

findings highlight how important effective 

educational plans are to enable people with 

haemophilia to fully understand GT and 

make an informed choice, but also show 

how durability and safety are key concepts 

that drive decision-making. [SP043] 

As part of the big picture for GT, it is important to look at considerations, 

including treatment expectations, specialties included in the HTC, and 

managing steroids. 

Brian O’Mahony – a patient working with 

the Irish Haemophilia Society – gave an oral 

presentation looking at what patients and 

payers should expect from GT. He began by 

noting that a key aspect for patients is setting 

and managing expectations, which should be 

based on realistic conversations with HCPs. 

This includes a person’s experience of living 

with haemophilia, their joint status, ABR, QoL, 

and activities and goals. Each patient should 

be given a clear understanding of knowns 

and unknowns, and be aware of long-term 

monitoring and follow-up requirements, 

including lifestyle implications in terms of 

alcohol and exercise. There should be solid 

arrangements to manage the journey, 

with clear coordination and roles in the 

hub-and-spoke, plus logistical arrangements 

to ensure the patient can comply with all 

monitoring requirements. Brian O’Mahony 

referred to a recent Canadian survey on 

haemophilia GT, which showed that 41% of 

respondents wanted to be sure of the Factor 

level they would achieve; this could represent 

a significant barrier to uptake when expression 

varies significantly. To address this, information 

and education is needed for individual 

comprehension levels across a multitude of 

platforms. The patient must be fully informed 

in a shared and objective decision-making 

process, and make an individual choice based 

on their personal needs and circumstances. 

Moving on to consider payers, Brian O’Mahony 

pointed out that important questions revolve 

around whether GT would pass a classic health 

technology assessment and cost-effectiveness 

threshold, and whether it is possible to 

extrapolate the potential durability of response. 

14 15


Potential outcomes for payers 

Meaningful 

Accessible 

Timely 

Measurable 

Robust 

Predictable 

Clotting 

factor 

consumption 

Factor 

expression 

Annual 

bleeding 

rate 

(ABR) 

Currently, price indications suggest that 

one-time GT dosing is equivalent in cost to 

4–5 years’ prophylaxis with an EHL Factor 

product. The outcome of an ICER evaluation 

in the US suggested that value should not 

be determined exclusively by long-term cost 

offsets, since the current standard of care is 

priced excessively highly. There is a budget 

impact for a high one-off cost, but ultimately 

payers want GT to be affordable, with a cost 

no greater than current therapies. There 

remains concern about paying for uncertain 

outcomes, with questions around durability 

and expression, and the need for residual 

CFC which may be required. A solution to 

some of the challenges posed is alternate 

funding models, such as an annuity-based 

staged payment, coverage with evidence 

development, or outcomes-based rebates. 

Potential outcomes could be a decrease in 

use of Factor or emicizumab, with a resultant 

cost offset. Another possible outcome measure 

could be Factor expression level, with a defined 

threshold above which full payment will be 

made, and one for partial or no payment. 

These outcomes are easy to measure, will 

Annual joint 

bleeding 

rate 

(AJBR) 

Joint 

health 

(e.g. HJHS) 

/ ultrasound 

Generic 

QoL tools 

(e.g. EQ-5D, 

SF36) 

Disease 

specifc 

QoL tools 

(e.g. PROBE, 

Haemo-QoL) 

Brian O’Mahony 

be routinely monitored, and can be easily 

adjudicated in the event of a dispute. Other 

potential outcomes for a payment model such 

as ABR, HJHS, or HRQoL are more subjective, 

and difficult or intrusive to measure and 

monitor. Brian O’Mahony concluded that, 

ultimately, innovation in payment schemes and 

risk-sharing agreements will allow payers to 

manage budget whilst improving long-term 

outcomes and future-proofing advancements 

in care for people with haemophilia. 

Mark Gurnell from the University of 

Cambridge, UK, gave a presentation 

focused on dealing with steroid side effects 

and withdrawal. He outlined that there are 

consequences of excess glucocorticoid 

exposure, with multiple possible 

manifestations and complications, even 

with short-term use. This includes bone 

and ophthalmic AEs, and cardiometabolic 

complications such as dyslipidaemia, heart 

failure, or type 2 diabetes. The chance of 

these is significantly increased above a 

cumulative dose of 500 mg – a threshold 

that is quickly reached and exceeded at 

high daily dosages. This means regular 

monitoring is needed during steroid therapy, 

including the tapering and withdrawal period. 

Dr Gurnell pointed out that one key issue 

with prolonged steroid use is suppression 

of the hypothalamic-pituitary-adrenal axis, 

causing cortisol deficiency; this secondary 

deficiency can be hard to identify, and has 

many non-specific symptoms such as fatigue 

or generalised aches and pains. The amount 

of steroid that can be taken before this axis 

is permanently affected is very variable. With 

this is mind, there is clearly a need to safely 

withdraw oral corticosteroids, and be able to 

assess and manage adrenal insufficiency. 

Just 1 week of steroids at a dose of >40 mg/day 

is enough to switch the axis off, and requires 

tapering. Gradual withdrawal should also be 

considered in patients who have been given 

repeated doses in the evening, those who 

Monitoring in patients receiving oral corticosteroid 

Monitoring requirements 

Blood pressure* 

Bodyweight* † 

Body mass index* 

have been treated for more than 3 weeks 

or recently received repeated courses, as 

well people who have taken a short course 

within 1 year of stopping long-term therapy. 

Assessment of axis function commonly 

requires a cortisol test; this should be done 

first thing in the morning to account for 

diurnal variation, and with exogenous steroid 

withheld on the day of the test. If a patient has 

adrenal insufficiency they should be referred 

to endocrinology. In conclusion, Dr Gurnell 

noted that oral corticosteroid therapy may 

be associated with significant AEs, especially 

when used at high dosages, or for long-term 

therapy or repeated courses. As a general 

rule, aim for the lowest dose for the shortest 

possible period, and perform formal testing 

for adrenal insufficiency once steroids have 

been weaned to a physiologic dose equivalent 

and complete discontinuation is anticipated. 

Frequency 

Every appointment 

Regularly 

Regurarly 

Optometrist assessment for glaucoma and cataracts* Every 6–12 months § 

HbA1c or fasting glucose level* ‡ 

Triglycerides and potassium* 

Adrenal suppression 

Osteoporosis risk 

Falls risk assessment 

Adverse effects 

(cardiovascular, endocrine/metabolic, GI, MSK, 

immunological, neurological, psychiatric, ophthalmic) 

Drug interactions 

Adapted from: NICE CKS Corticosteroids – Oral 

After 1 month then every 3 months 

After 1 month then every 6–12 months 

As indicated (especially during tapering to lower dosages) 

Periodically (and consider bone prophylaxis) 

Where appropriate 

Every appointment 

Every appointment and when medications changed 

*Ensure baseline measurements are taken before treatment; † Include height measurements for children 

and adolescents every 6 months and plot on growth chart; ‡ Monitor patients with diabetes more closely; 

§ 

Arrange earlier in patients with cataracts. 

Professor Mark Gurnell 

16 17


In an oral presentation, Vincenzo La Mura 

from the University of Milan, Italy, looked at 

why HTCs need a hepatologist. He noted that 

chronic hepatitis can be a multi-stage liver 

stage, and any hepatitis may evolve towards 

cirrhosis, with risks for portal hypertension, 

HCC, and organ failure. Critically, there 

is a high prevalence of viral hepatitis in 

people with haemophilia. In addition, HIV 

co-infection accelerates liver disease. This 

results in 20–30% of people with haemophilia 

developing end-stage liver disease, 

which can be difficult to transplant due to 

comorbidities. Dr La Mura emphasised that 

liver disease is the most common cause of 

death in people with haemophilia, but pointed 

out that there are successful vaccinations 

and anti-viral treatments, which makes 

collaboration between hepatologists and 

haematologists important. He suggested 

that this collaboration can be achieved either 

via a referral-based model or a screening 

programme with in-house follow-up – 

essentially where the hepatologist is on 

call versus included in the HTC as a staff 

member. Hepatological screening data from 

haemophilia patients at one centre in Milan 

show at least one potential risk factor in 

82% of people. The study also revealed signs 

suggestive of advanced fibrosis or cirrhosis 

in 16% of the HCV-exposed population, and 

several HCC cases. Dr La Mura argued 

that these findings support the need for 

hepatologists in HTCs: risk factors are 

frequent in people with haemophilia, 

and detecting and treating liver disease 

needs a specialist. 

Rasko et al. shared a poster examining 

the seroprevalence of NAb against AAV 

serotypes of relevance to GT in Europeans. 

The authors acknowledged that there are 

concerns that pre-existing NAb against AAV 

serotypes may interfere with GT. This subset 

analysis of a noninterventional, observational, 

retrospective, cross-sectional study focused 

on NAb prevalence against six AAV serotypes 

in 252 people from France, Germany, Italy, 

Spain, and the UK. Serum samples from 

the Pfizer Biobank were analysed from 

participants in previous non-GT clinical 

studies. NAb seroprevalence for the six 

AAV serotypes was estimated at a range of 

dilutions (from 1:1 to 1:50,000). At 1:1 dilution, 

NAb prevalence across countries ranged 

from 68.1–81.0% for AAV1; 53.2–71.4% for 

AAV5; 61.7–76.2% for AAV6; 57.4–69.0% for 

AAV8; 57.4–69.0% for AAV9; and 55.3–69.0% 

for AAVRh74var. Trends in NAb prevalence 

were similar in France, Germany, Italy, and 

the UK, but generally higher in Spain. At 1:4 

dilution, NAb prevalence was lowest for AAV5 

(Italy 19.1%, France 32.8%) and highest for 

AAV1 (Germany 52.0%, Spain 61.9%). Mean 

NAb titres (1/dilution) varied by country and 

were generally higher for AAV1 (Spain 110.2, 

France 212.6) and lower for AAV5 (Italy 5.3, 

France, 13.2). This analysis provides insight 

into the seroprevalence of NAbs against six 

different and clinically relevant AAV serotypes 

in adults across five European countries. The 

results shared in this poster suggest there is 

variation in seroprevalence geographically for 

a given AAV, as well as across different AAVs 

within a given country, which warrants further 

investigation on aetiology. [PO164] 

Non-Factor Product Updates 

Agents such as emicizumab and fitusiran have novel mechanisms of action, and 

may play an important role in restoring haemostasis in people with haemophilia. 

Pipe et al. investigated emicizumab prophylaxis 

for the treatment of infants with severe 

haemophilia A without FVIII inhibitors, 

based on an interim analysis of HAVEN 7 – 

a Phase 3b, open-label study in infants aged 

12 months or younger without FVIII inhibitors. 

Infants received emicizumab 3 mg/kg weekly 

for 4 weeks, then 3 mg/kg every 2 weeks 

for 52 weeks. Infants could stay on this dose 

or switch to 1.5 mg/kg weekly or 6 mg/kg 

every 4 weeks for the 7-year follow-up. 

At the data cut-off 54 infants received at least 

1 dose, with median treatment duration of 

42.1 weeks. Overall, 77 bleeds had occurred 

in 31 infants; of these 88.3% were traumatic, 

5.2% procedural, and 6.5% spontaneous. 

Overall, 14 treated bleeds – all traumatic – 

were reported in 12 infants, and none 

had more than 2 treated bleeds. Mean 

model-based ABRs for treated bleeds, all 

bleeds and treated joint bleeds were 0.4, 1.9, 

and 0.1, respectively. In total, 77.8% of infants 

had zero treated bleeds, while 42.6% had no 

bleeds at all. With regards safety, the poster 

showed that 92.6% of infants had at least 1 AE; 

16.7% of these were injection-site reactions. 

No AEs led to changes in or withdrawal 

from emicizumab. In total 12 serious AEs 

were reported in 8 infants, but none were 

considered to be related to emicizumab. 

No deaths, thrombotic events, or thrombotic 

microangiopathies have been reported. None 

of the 48 infants evaluable for immunogenicity 

tested positive for ADAs. Evaluable PK data in 

52 infants showed mean emicizumab trough 

concentrations increased during loading and 

were maintained, slightly above 60 μg/mL. 

The authors conclude that this interim analysis 

suggests that emicizumab is efficacious and 

well tolerated in infants with haemophilia A 

without FVIII inhibitors. [LCTR01] 

Kenet et al. shared results from a subgroup 

analysis of fitusiran efficacy and safety in 

adolescents with haemophilia, with or 

without inhibitors, from three Phase 3 trials – 

ATLAS-INH, ATLAS-A/B and ATLAS-PPX. 

As background they described how in 

ATLAS-INH and ATLAS-A/B, subjects with 

or without inhibitors, respectively, were 

randomised 2:1 to once-monthly 80 mg 

fitusiran prophylaxis or on-demand BPA 

(ATLAS-INH), or CFC (ATLASA/B) for 9 months. 

In ATLAS-PPX, subjects with or without 

inhibitors continued their prior CFC/BPA 

prophylaxis for 6 months before switching 

to monthly fitusiran prophylaxis for 7 months. 

Overall, 43 adolescents were analysed across 

the three studies. The results showed that 

median ABR was 1.7 (ATLAS-INH) and 

3.4 (ATLAS-A/B) in the fitusiran arm versus 

18.4 and 16.8 in the on-demand BPA and 

CFC arms, respectively. In ATLAS-PPX, 

median ABR was 0.0 in the fitusiran 

prophylaxis period versus 2.2 in the CFC/BPA 

prophylaxis period. Fitusiran improved HRQoL 

with a mean change in transformed total score 

from baseline to Month 9 of -18.2 and -10.8 

18 19


versus -2.1 and 4.3 in the on-demand BPA 

and CFC arms of ATLAS-INH and ATLAS-A/B, 

respectively. In ATLAS-PPX, the mean change 

in transformed total score was -4.3 in the 

CFC/BPA prophylaxis period versus -6.3 in 

the full trial period. The poster stated that the 

safety profile of fitusiran in adolescents was 

consistent with that in adults, and showed 

that the most common treatment-emergent 

AEs in the fitusiran group in ATLAS-INH 

were URTI (36.5%), increased ALT (27.3%), 

increased blood alkaline phosphatase 

(27.3%); in ATLAS-A/B the most common 

were arthralgia (22.2%) and increased blood 

bilirubin (22.2%). There were no thrombotic 

events in ATLAS-A/B or -PPT; however, 

3 events were reported in 1 fitusiran participant 

in ATLAS-INH, but these were assessed as 

unlikely related to the study drug. The poster 

conclusions state that in adolescents with 

haemophilia A or B, with or without inhibitors, 

fitusiran prophylaxis demonstrated an 

improvement in bleeding phenotype across 

the three trials examined. By covering 

10 domains and having shown decreases 

in transformed total score, the Haemo-QoL 

supports broad improvements in HRQoL with 

fitusiran prophylaxis. In addition, the benefit– 

risk assessment was favourable, and supports 

further investigation into efficacy and safety in 

adolescents with haemophilia. [PO119] 

In a session on the latest clinical trial results, 

Robert Klamroth from the Vivantes Klinikum 

im Friedrichshain in Berlin, Germany, 

presented findings from an exploratory 

analysis to assess FVIII haemostatic 

equivalency of the revised fitusiran dose and 

regimen. As background, he drew attention to 

data from ATLAS-INH and ATLAS-A/B, which 

showed that fitusiran prophylaxis resulted 

in a sustained reduction in antithrombin, 

with constant lowering of around 90% from 

1 month onwards – but this did not reach the 

lower level of peak thrombin generation seen 

in healthy volunteers. A simulation based on 

PK/PD modelling identified a revised dose 

and regimen which targeted an antithrombin 

range of 15–35%. To better understand the 

haemostatic Factor equivalency of fitusiran 

prophylaxis, a QSP model was developed to 

investigate thrombin generation in people 

with haemophilia. This model was validated 

by comparing predicted simulated TGA traces 

with experimental spike-in data, based on the 

15–35% range. Professor Klamroth explained 

how peak thrombin levels observed at different 

steady-state antithrombin ranges in pooled 

Phase 1/2 fitusiran clinical studies were 

plotted. A population of 1,000 virtual people 

with severe haemophilia A was generated 

based on calibration of the QSP model to 

individual patient data from completed 

fitusiran clinical studies, which showed that 

peak thrombin at therapeutic antithrombin 

levels of 15–35% with fitusiran was similar 

to peak thrombin associated with 20–40% 

of FVIII in people with haemophilia A. 

Professor Klamroth concluded that fitusiran 

prophylaxis results in sustained lowering 

of antithrombin and increased thrombin 

generation in people with haemophilia with 

and without inhibitors, suggesting that fitusiran 

has the potential to rebalance haemostasis 

and provide continuous and sustained 

steady-state bleed protection. A revised 

fitusiran dose regimen targeting antithrombin 

levels at 15–35% is being evaluated in ongoing 

Phase 3 trials, with the aim of enhancing 

the benefit–risk profile of fitusiran. 

Assays 

Interpretation of FVIII activity levels when measuring GT-derived 

BDD-FVIII protein is complicated by the systematic discrepancies reported 

by the two common assays used to measure FVIII activity: OSA and CSA. 

Rojas et al. shared a poster on increased 

thrombin generation of GT-derived FVIII 

in patients administered SPK-8011 

(dirloctocogene samoparvovec). Previous 

results demonstrated that patients 

administered SPK-8011 have FVIII activity 

levels approximately 1.5-fold higher via OSA 

compared to CSA; however, it is yet to be 

determined if one assay is more reflective of the 

clinical benefit of GT-derived FVIII. To inform 

this issue, an investigation was undertaken to 

look at whether GT-derived FVIII demonstrated 

altered activity in TGA. As presented in the 

poster, analysis in patient plasma showed that 

SPK-8011-produced FVIII increased peak and 

total thrombin generation relative to FVIII in 

pooled normal plasma at comparable protein 

levels. The authors hypothesise that assays 

may show discrepant sensitivity to differences 

in FVIII specific activity, with those assessing 

global coagulation (OSA and TGA) more 

accurately capturing a potential enhancement 

in the downstream function of FVIII. Additional 

research to address this hypothesis is 

critical to inform the selection of assays 

for measuring GT-derived FVIII. [PO032] 

Obregón et al. shared a poster on the 

relationship between OSA and CSA 

discrepancies, and genetic analysis of 

the F8 gene in patients with non-severe 

haemophilia A. They noted that 30% of 

patients with mild haemophilia A show 

discrepancy in FVIII between OSA (FVIII:C1) and 

two-stage CSA (FVIII:CR). This observational, 

ambispective, and multicentre study 

determined FVIII:C1 and FVIII:CR in 52 patients 

from 9 Spanish hospitals. TGT was evaluated 

in platelet poor plasma, and mutation analysis 

performed by direct sequencing on individuals 

with discrepancy between the two assays. 

Results showed median FVIII:CR of 20.3% 

was higher than FVIII:C1 of 17.5% (p


LIST OF ABBREVIATIONS 

AAV – adeno-associated virus 

ABR – annualised bleeding rate 

ADA – anti-drug antibody 

AE – adverse event 

AIR – annualised infusion rate 

ALT – alanine aminotransferase 

BDD – B-domain deleted 

BPA – bypassing agent 

CFC – clotting factor concentrate 

CI – confidence interval 

CSA – chromogenic assay 

EAHAD – European Association for Haemophilia 

and Allied Disorders 

EHL – extended half life 

EQ-5D-5L – EuroQol 5 dimensions health 

questionnaire 

FIX – Factor IX 

FVIII – Factor VIII 

gc – genome copies 

GT – gene therapy 

GTR – Gene Therapy Registry 

HAART – highly active antiretroviral therapy 

Haemo-QoL – haemophilia-specific quality of 

life questionnaire 

HbA1C – haemoglobin A1C 

Hem-A-QoL – Haemophilia Quality of Life 

Questionnaire for Adults 

HCC – hepatocellular carcinoma 

HCV – hepatitis C virus 

HCP – healthcare professional 

HJHS – haemophilia joint health score 

HRQoL – health-related quality of life 

HTC – haemophilia treatment centre 

IFN – interferon 

IL – interleukin 

ITT – intention to treat 

LNP – lipid nanoparticle 

LSEC – liver sinusoidal endothelial cell 

mTOR – mammalian target of rapamycin 

NAb – neutralising antibody 

OSA – one-stage clotting assay 

PD – pharmacodynamic 

PK – pharmacokinetic 

QoL – quality of life 

QSP – quantitative systems pharmacology 

SD – standard deviation 

TGA – thrombin generation assay 

TGT – thrombin generation test 

VAS – Visual Analog Scale 

vg – vector genomes 

VWF – von Willebrand factor 

WFH – World Federation of Hemophilia 

22

EAHAD 2023 Congress Review

Create successful ePaper yourself

Delete template?

Save as template?