Patient experience with acute hepatic porphyria before and after long-term givosiran treatment in a qualitative interview study
Publication Details
Molecular Genetics and Metabolism Reports
March 2025
Author(s)
Hetanshi Naik1, Michelle Brown2, Stephen Meninger3, Stephen Lombardelli4
Affiliations
1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2RTI Health Solutions, Research Triangle, NC, USA; 3Alnylam Pharmaceuticals, Cambridge, MA, USA; 4Alnylam Pharmaceuticals, Maidenhead, UK
Abstract
Background:
Acute hepatic porphyria (AHP) is characterized by debilitating and potentially life-threatening neurovisceral attacks, possible chronic symptoms, and long-term complications. In a phase 1/2 open-label extension (OLE) study and the phase 3 ENVISION study, givosiran led to sustained improvement in annualized attack rate and quality of life (QOL) measures. To capture the patient experience of symptoms and impacts of AHP, and any changes experienced during treatment with givosiran, qualitative interviews were conducted with study participants.
Methods:
Participants who continued givosiran treatment after completing the phase 1/2 OLE study and the phase 3 ENVISION study participated in semi-structured interviews (i.e., loosely structured interviews on a predetermined topic without strict adherence to wording or order of questions) in 2022 that were developed and executed by RTI Health Solutions. Transcripts were assessed using thematic analysis methods. Authors/investigators categorized symptoms as likely acute attack-related or chronic based on the participants' descriptions. Select clinical trial results(baseline characteristics and QOL scores from the phase 1/2 and ENVISION studies) from interview participants were compiled.
Results:
Duration of givosiran treatment in the 21 participants at the time of interview was approximately 4–5 years (mean [SD], 51.8 [7.9] months; median [range], 49.7 [41.4, 69.1] months). Participants reported experiencing AHP symptoms prior to the phase 1/2 OLE or phase 3 studies, including abdominal pain (n = 20/21 [95 %]) and fatigue (n = 20/21 [95 %]), with impacts including work/school (n = 21/21 [100 %]) and family and intimate relationships (n = 20/21 [95 %]). Post-treatment, participants reported improvements in symptoms including abdominal pain (n = 20/20 [100 %] participants), fatigue (n = 20/20 [100 %]), and nausea (n = 19/19 [100 %]), and in impacts, including family and intimate relationships (n = 20/20 [100 %]) and work/school (n = 19/21 [90 %]). Most participants (n = 19/21 [90 %]) used opioids prior to the trials, and many reported stopping opioids (n = 10/17 [59 %]) or using a lower dose (n = 4/17 [24 %]). Participants reported complete relief of certain symptoms, including vomiting (n = 8/11 [73 %]), nausea (n = 10/15 [67 %]), and abdominal pain (n = 8/19 [42 %]). Participants with complete relief of pain or cessation of opioid use tended to be younger and more recently diagnosed, with higher baseline EuroQOL visual analog scale scores during the clinical trials. Participants with prior hemin prophylaxis at entry into the clinical trialswere more likely to have experienced abdominal pain, neuropathic pain/paresthesia, and gastrointestinal symptoms before the study, and were generally more or as likely to have complete relief of these symptoms (e.g., n = 6/8 [75 %] participants with prior hemin prophylaxis reported complete relief of abdominal pain vs n = 2/11 [18 %] participants without prior hemin prophylaxis). All participants reported being “very satisfied” with givosiran.
Conclusions:
Participants reported meaningful improvements in AHP symptoms, increased QOL, and reduced opioid use with long-term monthly givosiran treatment.
PMID
39811158
DOI
10.1016/j.ymgmr.2024.101174
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