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
A post-hoc analysis to assess reduction in pain and analgesic use during and between porphyria attacks.
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. 
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. 
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.
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.