Phase 2 Study to Test Bitopertin for 2 Types of Cutaneous Porphyrias

Preliminary data from Australian BEACON trial are expected by mid-2023

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Disc Medicine has launched a Phase 2 trial of bitopertin, an investigational oral treatment for erythropoietic porphyrias.

Dubbed BEACON, the open-label trial will investigate the safety, tolerability, and efficacy of  multiple doses of bitopertin in about 20 patients with erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) at sites in Australia. Preliminary trial data are expected in the first half of 2023.

“The initiation of the BEACON phase 2 study is an important milestone as it marks the first time bitopertin will be evaluated as a potential, disease-modifying therapy in patients with porphyria,” John Quisel, PhD, CEO at Disc Medicine, said in a press release.

“I want to thank our entire team for the tremendous effort that has brought us to this point and for their tireless dedication to patients,” Quisel added.

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As with other porphyria types, EPP and XLP are caused by mutations in genes involved in the production of heme, a molecule that helps transport oxygen through the body. As a result, intermediate byproducts, called porphyrins, accumulate in cells. For EPP patients, these disruptions result from mutations in the FECH gene, while in XLP, they are caused by ALAS2 mutations.

In both types, protoporphyrins are activated in response to light, resulting in symptoms such as extreme light hypersensitivity, pain, and tissue damage. Patients are also at an increased risk of developing hepatobiliary disease, which encompasses disorders involving the liver, bile ducts, and gallbladder.

“EPP and XLP are severe, debilitating and rare diseases that impact multiple dimensions of patients’ lives, spanning severe and painful phototoxic reactions [light sensitivity], complications of hepatobiliary disease, and a major toll on psychosocial development and quality of life,” said Robert Desnick, MD, PhD, inaugural chair emeritus of the department of genetics and genomics at the Icahn School of Medicine at Mount Sinai in New York City.

“There is an immense need for novel therapies, particularly ones that address the underlying pathophysiology [disease mechanisms],” added Desnick.

What is bitopertin?

Bitopertin is an oral selective inhibitor of a protein called glycine transporter 1 (GlyT1) that is designed to modulate heme production. GlyT1 resides on red blood cells, where it works as a transporter to supply cells with a molecule called glycine, which is essential for heme production.

By limiting the amount of glycine available to red blood cells, bitopertin is thought to regulate heme production and, consequently, the buildup of porphyrins that underlie EPP and XLP.

The investigational treatment was originally developed by Roche for schizophrenia. Disc entered a licensing agreement with Roche in 2021 to develop and commercialize bitopertin for porphyria.

Data from preclinical studies showed that bitopertin could reduce the accumulation of protoporphyrin IX (PPIX), a porphyrin that drives EPP and XLP symptoms, according to Disc. Bitopertin has been deemed safe in clinical trials involving more than 4,000 healthy volunteers and patients with psychiatric and blood disorders, the company stated.

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BEACON participants will receive 20 or 60 mg of oral bitopertin once daily for 24 weeks, or about six months. Participants will then be able to continue treatment with bitopertin for another 24 weeks.

In addition to evaluating safety, tolerability, and pharmacokinetics — the treatment’s movement into, through, and out of the body — BEACON will assess changes in PPIX levels with bitopertin.

Other tests will be conducted to evaluate the treatment’s effects on light sensitivity, daylight tolerance, and pain. Biomarkers of hepatobiliary disease will be measured in an exploratory manner.

“We are excited by the initiation of this clinical trial of bitopertin and its potential effects on PPIX, the molecular driver of these porphyrias and a major determinant of disease severity,” Desnick said.