Preventive treatment cut attack risk in small acute porphyria trial

Preventive treatment with intravenous hemin — a therapy commonly used to treat acute porphyria attacks — reduced attack risk over the following week in people with acute hepatic porphyria who received their scheduled preventive dose rather than placebo, according to results from a small clinical trial.

“This randomized, double-blinded, placebo-controlled pilot study is the first, to our knowledge, to demonstrate efficacy of intravenous hemin for prevention of acute attacks of AHP [acute hepatic porphyria],” the researchers wrote.

The study, “Intravenous hemin for prevention of frequent attacks of acute hepatic porphyria – a double-blind placebo controlled pilot study,” was published in Molecular Genetics and Metabolism.

Hemin may help prevent acute porphyria attacks

Porphyrias are a group of genetic disorders caused by problems in the body’s production of heme. These problems can cause porphyrins and their precursors — molecules used to make heme — to build up to toxic levels. Acute hepatic forms of porphyria are characterized by sudden, potentially severe attacks of symptoms associated with the buildup of porphyrins and their precursors.

Intravenous hemin replenishes heme in liver cells, which helps suppress the first step in heme production and rapidly lowers elevated levels of porphyrins and their precursors. Formulations of intravenous hemin are available in the U.S. as Panhematin and in Europe as Normosang; both formulations are sold by Recordati Rare Diseases.

Intravenous hemin is a mainstay of care for treating acute attacks in people with acute hepatic porphyrias. Doctors also sometimes give it regularly to help prevent attacks, but controlled evidence supporting this preventive use has been limited.

The researchers noted that randomized, placebo-controlled trials of hemin for treating ongoing acute attacks have been difficult to conduct. They pointed to one earlier blinded, placebo-controlled trial of heme arginate that was underpowered and did not show statistically significant benefits.

The researchers said that acute attacks can be severe and potentially life-threatening, and that blinded treatment can delay effective rescue therapy and increase patients’ risk. Testing hemin for prevention can reduce some of those challenges because patients can receive their scheduled study treatment when they are not having an attack, with rescue hemin available promptly if an attack occurs. That was the approach used in this study.

“We considered that a study of attack prevention by a single dose of hemin or placebo in patients already on heme prophylaxis and without current symptoms would have fewer such design complexities and also provide for administration of prompt rescue treatment with open-label hemin should an attack occur,” the scientists wrote.

Trial tested one scheduled hemin dose against placebo

This trial enrolled 13 people with acute hepatic porphyria — eight with acute intermittent porphyria (AIP) and five with variegate porphyria (VP). All were already receiving preventive intravenous hemin because they had a history of frequent attacks.

The trial (NCT02922413) had planned to enroll 20 participants, but enrollment was closed after 13 because eligible patients became increasingly difficult to recruit, the researchers said.

For the trial, participants received either their next scheduled preventive hemin dose or placebo instead of that dose. Seven received hemin and six received placebo. Participants and most study staff did not know which treatment was given. Arrangements were made in advance for prompt rescue treatment with hemin if an attack occurred.

Over the next week, one of the seven patients given hemin had an attack, compared with five of the six given placebo. The six attacks were treated promptly and resolved within several days. No other adverse events were reported.

The researchers said patients already receiving preventive hemin were significantly more likely to have an attack when placebo was substituted for a scheduled hemin dose.

The team noted that the results support previous open-label observations suggesting hemin prophylaxis can help prevent frequent attacks in some people with acute hepatic porphyria. The researchers said the new trial provides controlled evidence of benefit in patients already receiving preventive hemin.