Reduction in Pain During and Between Attacks in Patients with Acute Hepatic Porphyria Treated with Givosiran: A Post-Hoc Analysis of the Phase 3 ENVISION Study
Susana Monroy1, Raili Kauppinen2, Hung-Chou Kuo3, Jeeyoung Oh4, Ole Hother-Nielson5, Mary-Jean Fanelli6, Zhaowei Hua6, Qiuling He6, John J. Ko6, Amy Simon6, David Rees7
1Instituto Nacional de Pediatría, 2Helsinki University Central Hospital, 3Chang Gung Medical Foundation – Linkou Chang Gung Memorial Hospital, 4Konkuk University Hospital, 5Odense University Hospital, 6Alnylam Pharmaceuticals, 7King’s College Hospital
Objective:
A post-hoc analysis to assess reduction in pain and analgesic use during and between porphyria attacks.
Background:
Acute hepatic porphyria (AHP) is a family of rare genetic diseases resulting from enzyme deficiencies in heme biosynthesis. Clinical manifestations include potentially life-threatening neurovisceral attacks and chronic symptoms, with neuropathic pain being the cardinal symptom during and between attacks. In the ENVISION Phase 3 study, givosiran, an RNA interference therapeutic, reduced annualized attack rate (P<0.001), improved daily worse pain (secondary), decreased proportion of days with analgesics use (exploratory) and demonstrated a favorable benefit:risk profile. 
Design/Methods:
ENVISION (NCT03338816), a randomized, double-blind placebo-controlled trial evaluated the efficacy and safety of subcutaneous givosiran in AHP patients (N=94). Daily worst pain, analgesic use (opioid and non-opioid), and the SF-12 health survey were obtained. Analyses are descriptive. 
Results:
In patients with at least 1 attack, a lower proportion on givosiran (41.7%) compared to placebo (63.2%) had severe pain (median pain score ≥7). During attack-free periods, givosiran treatment resulted in reduced daily worst pain scores compared to placebo.  This pain reduction was also accompanied by lower analgesic use. The SF-12 Bodily Pain domain demonstrated a greater improvement for givosiran (7.3) versus placebo (2.2) at Month 6, suggesting that the reduced pain had a functional impact in patients.
Conclusions:
AHP patients on givosiran showed reductions in pain during and between attacks compared to placebo along with decreased analgesic use supporting the potential benefit of givosiran as a disease modifying drug.