P1807 - EXPLORE Part B: A Prospective, International, Long-Term Natural History Study of Patients With Acute Hepatic Porphyria With Recurrent Symptoms

David M. Cassiman, MD, PhD¹, Raili M. Kauppinen, MD, PhD², Susana Monroy, MD³, Ming-Jen Lee, MD⁴, Herbert L. Bonkovsky, MD, FACG⁵, Manish Thapar, MD⁶, Encarna Guillén-Navarro, MD, PhD⁷, Zhaowei Hua, PhD⁸, Marianne T. Sweetser, MD, PhD⁸, Aneta V. Ivanova, MD, PhD^9
1University Hospital Leuven, Leuven, Vlaams-Brabant, Belgium; ²University Hospital of Helsinki, Helsinki, Uusimaa, Finland; ³Instituto Nacional de Pediatría de Mexico, Mexico City, Distrito Federal, Mexico; ⁴National Taiwan University Hospital, Taipei, Taipei, Taiwan; ⁵Wake Forest Baptist Health, Winston-Salem, NC; ⁶Thomas Jefferson University, Philadelphia, PA; ⁷University Hospital Virgen de la Arrixaca, IMIB, CIBERER-ISCIII, University of Murcia (UMU), Murcia, Murcia, Spain; ⁸Alnylam Pharmaceuticals, Cambridge, MA; ⁹St. Ivan Rilski University Hospital, Sofia, Sofiya, Bulgaria

Introduction: Acute hepatic porphyria (AHP) is caused by genetic defects in heme biosynthesis. Intravenous hemin is recommended for acute attacks and can be used prophylactically but has side effects. Gonadotropin-releasing hormone (GnRH) has been used prophylactically for women with recurrent premenstrual attacks, with variable efficacy. EXPLORE (NCT02240784) is a prospective, natural history study of patients with AHP with recurrent attacks. Part A followed patients for up to 12 months. Part B included optional long-term evaluation of pain intensity and changes in disease activity in eligible patients from Part A, and newly enrolled patients, for up to 3 additional years.

Methods: Patients with AHP with ≥1 attack in the prior 12 months or receiving hemin/GnRH prophylaxis were eligible for Part B. Pain intensity and impact were measured by Brief Pain Inventory (BPI) form (scale 0–10). Changes in disease activity were captured via questionnaires. Quality of life (QOL) was assessed by the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and the EuroQOL visual analog scale (EQ-VAS) (scale 0–100 for total scores of both questionnaires). Assessments were conducted by mail and confirmed by telephone every 3–6 months over 3 years.

Results: Overall, 136 patients (43 from Part A) were enrolled from 18 countries (mean age, 41 years; 90% female) and 90% had acute intermittent porphyria. In the 12 months prior to enrollment, all patients reported a median (range) of 3 (0–52) acute attacks, with 46% on hemin and/or GnRH prophylaxis. A subgroup with < 3 attacks a year (N=27) without prophylaxis had a median (range) of 1 (0–2) acute attack in the past 12 months. Most patients required hemin (70%) and pain medication (96%), including opioids (59%), during attacks, and most (85%) also had chronic symptoms. At baseline, mean worst pain and average pain scores (BPI form) were 3.6 and 3.3, respectively. Patients taking pain medications regularly (N=19) reported that, on average, only 42% of their pain had been relieved in the last 24 hours. Mean EQ-VAS score was 71 in the subgroup with < 3 attacks versus 63 in the subgroup with ≥3 attacks; mean EORTC Overall Health and QOL scores were 67 and 54, respectively.

Discussion: These data demonstrate that AHP patients with recurrent attacks, even those having fewer attacks, suffer from a high burden of disease, shown by chronic symptoms between attacks and impaired QOL.


Disclosures:
David Cassiman: Alnylam Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speaker's Bureau.
Raili Kauppinen: Orion Pharmaceuticals – Stockholder/Ownership Interest (excluding diversified mutual funds).
Susana Monroy: Alnylam Pharmaceuticals – Advisory Committee/Board Member. Recordati Rare Diseases – Consultant. Ultragenyx Pharmaceuticals – Speaker's Bureau.
Ming-Jen Lee indicated no relevant financial relationships.
Herbert Bonkovsky: Alnylam Pharmaceuticals – Grant/Research Support. Recordati Rare Chemicals – Consultant.
Manish Thapar: Alnylam Pharmaceuticals – Consultant, Speaker's Bureau.
Encarna Guillén-Navarro: Alnylam Pharmaceuticals – Advisory Committee/Board Member, Grant/Research Support. Biomarin – Advisory Committee/Board Member. UCB – Advisory Committee/Board Member.
Zhaowei Hua: Alnylam Pharmaceuticals – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Marianne Sweetser: Alnylam Pharmaceuticals – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Aneta Ivanova: Alnylam Pharmaceuticals – Advisory Committee/Board Member, Consultant. Recordati Rare Diseases – Advisory Committee/Board Member.


David M. Cassiman, MD, PhD¹, Raili M. Kauppinen, MD, PhD², Susana Monroy, MD³, Ming-Jen Lee, MD⁴, Herbert L. Bonkovsky, MD, FACG⁵, Manish Thapar, MD⁶, Encarna Guillén-Navarro, MD, PhD⁷, Zhaowei Hua, PhD⁸, Marianne T. Sweetser, MD, PhD⁸, Aneta V. Ivanova, MD, PhD⁹. P1807 - EXPLORE Part B: A Prospective, International, Long-Term Natural History Study of Patients With Acute Hepatic Porphyria With Recurrent Symptoms, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.