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Study Finds Unmet Need for Therapies for Recurrent Attacks of Acute Hepatic Porphyria


Data from EXPLORE, a prospective, multinational, natural history study, is used to characterize disease activity and clinical management of patients with acute hepatic porphyria (AHP) who experience recurrent attacks. The findings highlight the high unmet need for effective treatments.

Patients with acute hepatic porphyria (AHP) can experience neurovisceral attacks and other chronic symptoms that adversely impact day-to-day functioning. A new study published in Hepatology, the journal of the America Association for the Study of Liver Diseases, used data from EXPLORE, a prospective, multinational, natural history study, to characterize disease activity and clinical management of patients with AHP who experience recurrent attacks.

AHP is a group of rare, metabolic diseases caused by a mutation in the genes involved in heme biosynthesis.

In addition to experiencing acute neurovisceral attacks, patients with AHP experience debilitating chronic symptoms and long-term complications, such as liver disease, chronic kidney disease, and systemic arterial hypertension. Most patients have only a few neurovisceral attacks in their life, but some patients with the autosomal dominant acute intermittent porphyria type of AHP experience recurrent attacks.

“During attacks, patients typically present with multiple signs and symptoms due to dysfunction across the autonomic, central, and peripheral nervous systems,” the authors explained. “They often require hospitalization and pain relief with opioids.”

Hemin (lyophilized hematin in the United States and heme arginate in Europe) is the only approved treatment for acute attacks, and it is delivered intravenously. There are no pharmacotherapies that have been approved to prevent attacks, the authors noted. Instead, patients practice strategies such as trigger avoidance, early ingestion of carbohydrates, suppression of ovulation, and the off-label use of intravenous hemin prophylaxis.

However, use of prophylactic hemin has potential side effects and could result in potential complications after chronic use. As a result, there is a high unmet need for effective treatments.

The EXPLORE study included 112 patients with confirmed AHP who either had experienced 3 or more attacks in the previous 12 months or were receiving prophylactic treatment. The patients were followed for at least 6 months. Patients completed questionnaires during clinic visits that took place at baseline, month 6, and an optional month 12. They detailed their symptoms and treatment, their quality of life (QOL; using the EuroQoL 5-Dimensions questionnaire-5 levels), and health status. They were also subjected to physical examinations and laboratory assessments.

At baseline, the patients reported that in the 12 months previous, they had a median of 6 (range, 0-52) attacks. There were a broad array of symptoms and signs associated with the attacks, including pain, reported by 99% of patients, nausea (85%), and change in urine color (81%).

The majority of patients (84%) had received hemin treatment for attacks, and more than half (59%) of those patients reported side effects. More than half (55%) of all patients reported taking medications prophylactically at baseline. Of those patients, nearly half (46%) received hemin.

During the study, 6% experienced at least 1 adverse event, all mild or moderate in severity. Overall 86% of patients experienced at least 1 change in health status, such as headache, nasopharyngitis, influenza and systemic arterial hypertension, and fatigue, pyrexia, and extremity pain. Patients with recurrent attacks had low QOL at both baseline and throughout the study. At 12 months into the study, patients reported a mean of 3.6 emergency department visits and 5.1 overnight hospital stays.

“These results underscore the need for novel therapies that can reduce attacks, disease manifestations in between attacks, and improve patients’ ability to function on a daily basis,” the authors concluded.


Gouya L, Ventura P, Balwani M, et al. EXPLORE: a prospective, multinational, natural history study of patients with acute hepatic porphyria with recurrent attacks [published online September 12, 2019]. Hepatology. doi: 10.1002/hep.30936.

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