Abstract Details

Title 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

Topic Pain

Presentation(s) S24 - Pain and Palliative Care: Targeted Therapy in Chronic Pain Disorders (4:24 PM-4:32 PM)

Poster/Presentation
Number 003

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.

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

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.

Authors/Disclosures
Susana Monroy (Instituto Nacional de Pediatria) PRESENTER	Susana Monroy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Susana Monroy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Recordati. Susana Monroy has received personal compensation in the range of $0-$499 for serving as an Expert Witness for Recordati.
	No disclosure on file
	No disclosure on file
Jeeyoung Oh, MD, PhD	Dr. Oh has nothing to disclose.
	No disclosure on file
Mary-Jean Fanelli, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
John Ko, PharmD, MS (Alnylam)	Dr. Ko has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Dr. Ko has received personal compensation for serving as an employee of Novartis. Dr. Ko has received stock or an ownership interest from Alnylam Pharmaceuticals. Dr. Ko has received stock or an ownership interest from Novartis.
	No disclosure on file
	No disclosure on file