Abstract Details

Title EXPLORE: A prospective, multinational natural history study of acute hepatic porphyria patients with recurrent attacks

Topic General Neurology

Presentation(s) S27 - General Neurology: Improving Neurologic Care and the Impact of Therapeutics (1:22 PM-1:33 PM)

Poster/Presentation
Number 003

Background AHPs are rare, often misdiagnosed genetic diseases caused by a mutation in one of the enzymes of heme biosynthesis. This results in the accumulation of neurotoxic heme intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG), that can cause severe neurovisceral pain, life-threatening attacks and chronic debilitating symptoms (pain, nausea, fatigue). We report data updated ≥12 months.

Objective EXPLORE sought to characterize the disease activity and clinical management of patients with Acute Hepatic Porphyrias (AHPs) in the US and Europe.

Design/Methods EXPLORE (ClinicalTrials.gov Identifier: NCT02240784) is a prospective, international, observational natural history study and clinical management of patients with hepatic porphyrias with recurrent attacks (≥3 attacks/year) or who receive prophylactic treatment to prevent attacks. Patient medical history, physical examination and porphyrin biomarkers, and questionnaires on porphyria activity were collected.

Results

112 patients enrolled from 13 countries and were followed for 12 months. Mean age: 39 years, 89% female, 93% with acute intermittent porphyria, 4% variegate porphyria, and 3% hereditary coproporphyria. Patients reported a mean of 9.3 attacks in the 12 months prior to study, pain being the most common symptom, occurring in 99% of attacks. Mean attack duration was 7 days. Chronic symptoms were reported by 65% of patients, pain being the most frequent symptom. On-study attack rate was 3.7 attacks/person/year, of which 69% required treatment with hemin or a healthcare visit. For those patients on hemin prophylaxis, mean attack rate was 3.5 attacks/person/year. Mean ALA and PBG levels at screening (during non-attack) were markedly increased to 9 and 23 times the upper limit of normal, respectively.

Conclusions EXPLORE, the first international natural history study in patients with hepatic porphyria and recurrent attacks, demonstrates that patients suffer from attacks and chronic symptoms. Given morbidity and mortality, there remains an unmet need for novel therapies to prevent attacks and treat chronic symptoms.

Authors/Disclosures
PRESENTER	No disclosure on file
Robert Desnick, MD, PhD (Mount Sinai School of Medicine)	No disclosure on file
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Manisha Balwani	No disclosure on file
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John P. Phillips, MD (Mind Research Network)	Dr. Phillips has nothing to disclose.
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Amy Chan, MD (Dartmouth-Hitchcock Medical Center)	Dr. Chan has nothing to disclose.
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