PMID- 38020288
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 1939-4551 (Print)
IS  - 1939-4551 (Electronic)
IS  - 1939-4551 (Linking)
VI  - 16
IP  - 11
DP  - 2023 Nov
TI  - Assessment of HAE prophylaxis transition from androgen therapy to berotralstat: A 
      subset analysis of the APeX-S trial.
PG  - 100841
LID - 10.1016/j.waojou.2023.100841 [doi]
LID - 100841
AB  - BACKGROUND: Given the recent approval of oral berotralstat in several countries 
      for hereditary angioedema (HAE) prophylaxis, transition from long-term androgens 
      to berotralstat may occur in clinical practice. The open-label, Phase II APeX-S 
      trial provided an opportunity to assess the safety and effectiveness of 
      berotralstat in patients previously treated with differing durations of androgens 
      and shorter transition periods. Therefore, we examined the safety, effectiveness, 
      and impact on quality of life of berotralstat after prior androgen use in 
      patients from the APeX-S trial. Alanine aminotransferase (ALT) elevations were 
      also examined because of the association with androgen exposure and hepatic 
      function impairment. METHODS: We conducted an analysis of a subset of 39 patients 
      from the APeX-S trial aged >/=12 years with HAE due to C1 inhibitor deficiency 
      (HAE-C1-INH) with prior androgen use who discontinued androgen therapy within <60 
      days of receiving berotralstat. Patients received daily berotralstat (150 mg) and 
      were divided into subgroups for this analysis based on time between androgen 
      discontinuation and berotralstat commencement (<14 days versus 14 to <60 days). 
      RESULTS: Berotralstat was generally well tolerated, with nasopharyngitis (21%), 
      upper respiratory tract infection (15%), nausea (15%), diarrhea (15%), and 
      abdominal pain (10%) being the most common adverse events occurring in >/=10% of 
      the total subset. Only 7/145 (5%) of all APeX-S study patients with a prior 
      history of androgen therapy experienced ALT elevations, 6 of which were grade 3 
      or 4 toxicities. All 7 patients recovered without sequelae and belonged to the 
      subgroup of patients who transitioned <14 days after discontinuing androgens 
      (n = 18). A reduction in monthly attack rate versus Month 1 was observed over 12 
      months for all patients who transitioned from prior androgen therapy to 
      berotralstat prophylaxis in under 60 days, irrespective of duration of prior 
      androgen therapy or timing of transition (N = 39). Similarly, meaningful 
      patient-reported improvements from both Angioedema Quality of Life Questionnaire 
      and Treatment Satisfaction Questionnaire for Medication scores were achieved, 
      with a sustained benefit shown over the berotralstat treatment period. 
      CONCLUSIONS: Berotralstat treatment led to sustained HAE symptom control 
      irrespective of duration of prior androgen therapy or timing of transition. Most 
      patients safely transitioned from long-term androgens to berotralstat. Although 
      occurring in a small group of patients, liver-related adverse events following 
      berotralstat treatment may be associated with a shorter androgen washout period, 
      but further research is required to confirm this. CLINICAL TRIAL REGISTRATION: 
      NCT03472040. Retrospectively registered March 21, 2018.
CI  - (c) 2023 The Authors.
FAU - Peter, Jonny G
AU  - Peter JG
AD  - Division of Allergy and Clinical Immunology, Department of Medicine, University 
      of Cape Town, Cape Town, South Africa.
AD  - Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, 
      South Africa.
FAU - Desai, Bhavisha
AU  - Desai B
AD  - BioCryst Pharmaceuticals, Inc., Durham, NC, USA.
FAU - Tomita, Dianne
AU  - Tomita D
AD  - BioCryst Pharmaceuticals, Inc., Durham, NC, USA.
FAU - Collis, Phil
AU  - Collis P
AD  - BioCryst Pharmaceuticals, Inc., Durham, NC, USA.
FAU - Stobiecki, Marcin
AU  - Stobiecki M
AD  - Department of Clinical and Environmental Allergology, Jagiellonian University 
      Medical College, 10 Sniadeckich St, 31-531 Krakow, Poland.
LA  - eng
SI  - ClinicalTrials.gov/NCT03472040
PT  - Journal Article
DEP - 20231106
PL  - United States
TA  - World Allergy Organ J
JT  - The World Allergy Organization journal
JID - 101481283
PMC - PMC10665923
OTO - NOTNLM
OT  - Androgens
OT  - Angioedemas
OT  - Berotralstat
OT  - Hereditary
OT  - Treatment switching
COIS- Jonny G. Peter has received research funding from BioCryst Pharmaceuticals, Inc. 
      Dianne Tomita and Phil Collis are employees of, and own stocks in, BioCryst 
      Pharmaceuticals, Inc. Bhavisha Desai is a former employee of BioCryst 
      Pharmaceuticals, Inc. Marcin Stobiecki has received research funding from 
      BioCryst Pharmaceuticals, Inc.
EDAT- 2023/11/29 18:43
MHDA- 2023/11/29 18:44
PMCR- 2023/11/06
CRDT- 2023/11/29 14:41
PHST- 2022/12/02 00:00 [received]
PHST- 2023/10/18 00:00 [revised]
PHST- 2023/10/19 00:00 [accepted]
PHST- 2023/11/29 18:44 [medline]
PHST- 2023/11/29 18:43 [pubmed]
PHST- 2023/11/29 14:41 [entrez]
PHST- 2023/11/06 00:00 [pmc-release]
AID - S1939-4551(23)00101-1 [pii]
AID - 100841 [pii]
AID - 10.1016/j.waojou.2023.100841 [doi]
PST - epublish
SO  - World Allergy Organ J. 2023 Nov 6;16(11):100841. doi: 
      10.1016/j.waojou.2023.100841. eCollection 2023 Nov.