UEG Week Virtual 2021 Congress Review - 7

UEG Week Congress Review
Givosiran provides sustained and
continuous benefit in patients
with AHP
A 24-month analysis of the Phase 3 ENVISION study1
has
provided evidence that the aminolevulinate synthase 1-directed
small interfering RNA, givosiran, provides sustained and
continuous benefit over 2 years in patients with acute hepatic
porphyria (AHP). Patients who continued with givosiran
treatment in the open-label extension (OLE) of the ENVISION
study continued to benefit from the near-normal levels of
urinary disease markers, low acute attack rates and hemin use,
and improved quality of life achieved after 6 months of doubleblind
treatment.
The ENVISON study randomised 94 patients aged ≥12 years
with AHP who had an elevated level of urinary aminolevulinic
acid (ALA) or porphyobilinogen (PBG) (≥4 times the upper limit
of normal), and who had experienced at least two composite
porphyria attacks during the 6 months before baseline.1
Lactated Ringer's solution plus rectal
indomethacin prevents post-ERCP
pancreatitis
Patients
were randomised to receive monthly subcutaneous givosiran 2.5
mg/kg (n=48) or placebo (n=46) for 6 months, with the option to
continue givosiran 2.5 or 1.25 mg/kg in the OLE. Among the 89
patients with acute intermittent porphyria (the most common
form of AHP) who took part in the study, the median annualised
attack rate (AAR) (the primary endpoint) was 1.0 (IQR: 0.0-6.2)
in the givosiran group and 10.7% (IQR: 2.2-26.1) in the placebo
group - a relative difference of 90%.1 Attack rates remained low
during long-term treatment with givosiran. Among patients who
received continuous givosiran over 24 months (n=47), the median
AAR was 0.46 and the proportion of patients with zero attacks per
3-month intervals improved over the OLE period, with 82.6% of
patients attack-free at months >21-24 compared with 66.7% of
patients attack-free at months >3-6.
Continuous givosiran treatment led to a sustained lowering of
median urinary ALA levels to near normal and lowering of PGB
levels by >75% through month 24. The percentage of patients
with zero days of hemin use increased from 54.2% during
double-blind treatment to 68.1% during open-label treatment,
with median annualised days of hemin use of 0.0 and 0.2,
respectively. Patients experienced continued improvements in
quality of life and other patient-reported outcomes during open
label treatment.
The most common treatment-related adverse events (AEs)
reported with givosiran treatment were injection site reactions
(27/94 patients [29%]), nausea (19/94 patients [20%]), and
fatigue (12/94 patients [13%]). Serious AEs, which included
increased blood homocysteine, chronic kidney disease, device
breakage, pyrexia, and urinary tract infections, were reported
in 28 patients (30%).
" Givosiran is an exciting new treatment for patients with acute
hepatic porphyrias with [a] prior frequent history of attacks, "
concluded investigator and presenter, Herbert Bonkovsky,
from Wake Forest University and the North Carolina Baptist
Medical Center in Winston-Salem, USA.
Lactated Ringer's solution (LR) infusion in combination with
rectal indomethacin is more effective than either treatment
alone in preventing pancreatitis in patients who have
undergone ERCP, according to the results of a randomised,
double-blind study conducted in Algeria.
Researchers from the Central Hospital of the Army (HCA) in
Algiers randomised 210 patients at high risk of developing
post-ERCP pancreatitis to receive an LR infusion (1 litre prior
to the procedure and 3 mL/kg/hour during and for at least
4 hours after the procedure), rectal indomethacin, or both
treatments (n=70 per group). The primary endpoint of the study
was post-ERCP pancreatitis, defined using standardised criteria.
Baseline patient characteristics were well balanced between
treatment groups. All patients had at least one risk factor for
post-ERCP pancreatitis and 59% had more than one.
Post-ERCP pancreatitis occurred in four/70 patients (5.7%) in
the LR + indomethacin group compared with 12/70 patients
(17.1%) in the LR group (p=0.04) and seven/70 patients (10.0%)
in the indomethacin group (p=0.05). The differences between
the LR + indomethacin and indomethacin groups were not
statistically significant (p=0.06).
Readmission rates were significantly lower in the LR +
indomethacin group (two patients [2.8%]) compared with the
LR group (seven patients [10.0%]) (p=0.03). Five patients (7.1%)
in the indomethacin group were readmitted, but the betweengroup
differences were not statistically significant (p=0.07 for
indomethacin vs. LR and p=0.06 for indomethacin vs. LR +
indomethacin). No differences were found between the study
groups for the other secondary endpoints.
The investigators concluded that, in high-risk patients, the
" practical combination " of LR + indomethacin reduced the
incidence of post-ERCP pancreatitis and readmission rates
compared with LR or indomethacin alone.
1. Balwani M, et al. N Engl J Med 2020;382(24):2289-2301.
7

https://www.ueg.eu/library/efficacy-and-safety-of-givosiran-in-patients-with-acute-hepatic-porphyria-24-month-interim-analysis-of-the-phase-3-envision-randomized-clinical-trial/248008 https://www.ueg.eu/library/lactated-ringer-s-solution-in-combination-with-rectal-indomethacin-prevents-efficiently-post-ercp-pancreatitis-in-patients-at-high-risk-a-prospective-randomized-double-blinded-controlled-trial/248147

UEG Week Virtual 2021 Congress Review

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