Disc maps out US filing for porphyria drug bitopertin

Disc Medicine has charted a route to market for bitopertin, its drug candidate for rare disease erythropoietic protoporphyria (EPP), after meeting with the FDA.

Shares in the company gained almost 24% after it announced that the end of phase 2 meeting with the US regulator had firmed up plans for a phase 3 trial of bitopertin in EPP, as well as the potential for accelerated approval.

EPP is an inherited condition that leads to a deficiency of the enzyme ferrochelatase (FECH) used in haemoglobin synthesis. It results in the accumulation of protoporphyrins in red blood cells, particularly protoporphyrin IX (PPIX), which results in severe pain and swelling on exposure to the sun and some forms of artificial light like fluorescent lamps. In some cases, it can also cause liver and gall bladder disease.

Bitopertin is an orally administered GlyT1 inhibitor that is designed to modulate the biosynthesis of haem, a constituent of haemoglobin, and has been shown in studies to reduce PPIX levels in red blood cells.

Watertown, Massachusetts-based Disc has agreed with the FDA that it will use average monthly time in sunlight during the last month of a six-month treatment period as the primary endpoint in its planned phase 3 trial – to be called APOLLO – which it hopes to start in the middle of next year.

The trial will enrol subjects aged 12 and over with EPP, as well as a related condition called X-linked protoporphyria (XLP), and test a 60mg daily dose of bitopertin on the primary endpoint, as well as secondary measures including the rate of phototoxic reactions, cumulative total pain-free time in sunlight, and the patient global impression of change (PGIC) scale.

The FDA has also agreed that PPIX levels can serve as a surrogate marker to gauge the efficacy of the drug.

In its phase 2 AURORA trial involving 75 subjects with EPP and XLP, Disc showed that a once daily dose of 60mg bitopertin achieved a significant reduction in whole blood PPIX levels and improved measures of light tolerance compared to placebo.

Disc is also running a 26-subject open-label phase 2 study of bitopertin in patients with EPP and XLP, called BEACON, which was reported at last year's American Society of Haematology (ASH) annual congress.

Bitopertin has been awarded rare paediatric disease designation (RPD) by the FDA in May for the treatment of EPP. According to the American Porphyria Foundation (APF), EPP and XLP combined are the third most common porphyria, with an incidence of possibly two to five per million people, and are the most common porphyria in children.

At the moment, there is one approved treatment for EPP – Clinuvel Pharmaceuticals' Scenesse (afamelanotide) – but this works via a different mechanism, encouraging the production of melanin in the skin to protect it from phototoxic damage.

Scenesse was approved by the FDA in 2019 and in Europe in 2014, but has faced payer resistance, including in the UK. The drug accounts for the bulk of the Australian company's revenues, which reached A$95 million ($63 million) in fiscal 2024.