Bitopertin

Table of contents

• What is bitopertin?
• How does bitopertin work?
• Which conditions is bitopertin studied for?
• How is bitopertin given?
• What do the clinical trials show?
• What side effects are known?

What is bitopertin?

Bitopertin is an investigational small-molecule medicine developed by Roche and later by Disc Medicine. It belongs to the class of glycine transporter 1 inhibitors and is described in drug reference sources as an antianaemic and skin disorder therapy.^[3] The substance is also known by several development codes and alternative names, including DISC-1459, R-1678, RG 6718, RG-6178, RG1678, and RO-4917838.^[3] Bitopertin has received orphan drug designation, meaning it is intended for a rare disease.^[3] It is not yet authorised as a medicine; the trials registered in the EU Clinical Trials Information System and on ClinicalTrials.gov are investigating its effects.

How does bitopertin work?

Bitopertin works by inhibiting glycine transporter 1, a protein involved in the production of protoporphyrin IX (PPIX).^[3] In erythropoietic protoporphyria and X-linked protoporphyria, PPIX builds up in the body. When skin is exposed to light, this excess PPIX triggers a painful reaction known as phototoxicity. By reducing PPIX production, bitopertin is intended to make the skin less sensitive to sunlight. The clinical trials measure PPIX levels in whole blood to see whether the medicine has this effect.^[2]

Which conditions is bitopertin studied for?

• Erythropoietic protoporphyria (EPP) — a rare inherited condition in which a substance called protoporphyrin IX builds up in red blood cells, causing severe pain and burning of the skin within minutes of sun exposure.^[2][1]
• X-linked protoporphyria (XLP) — a related rare condition with the same type of painful light sensitivity, caused by a different genetic change but also leading to excess protoporphyrin IX.^[2][1]

How is bitopertin given?

In the registered trials, bitopertin is given as a 60 mg dose taken by mouth (oral use).^[2][1] The APOLLO trial compared this oral dose with a matching placebo, meaning some participants received an inactive tablet that looked the same.^[2]

What do the clinical trials show?

Two Phase 3 trials of bitopertin in EPP and XLP are registered. The APOLLO trial (NCT06910358) was a randomised, double-blind, placebo-controlled study that enrolled 150 participants and has been completed.^[2] Its main measures were the average monthly total time in sunlight without pain between 10:00 and 18:00 after 24 weeks of treatment, the percent change from baseline in whole-blood metal-free PPIX levels, and safety and tolerability assessed through adverse events and laboratory results.^[2] The HELIOS trial (NCT05883748) is a long-term study authorised to enrol 265 participants with EPP or XLP, including any FECH and ALAS2 genotypes.^[1] Its primary measure is the safety and tolerability of bitopertin over the long term, assessed by treatment-emergent adverse events, vital signs, physical examinations, and clinical laboratory parameters.^[1] Both trials included participants with either EPP or XLP, and both used the same 60 mg oral dose of bitopertin.^[2][1]

What side effects are known?

The available trial records list safety and tolerability as outcomes, but they do not report specific side effects in the data provided here. The APOLLO trial assessed adverse events and laboratory results over 6 months, and the HELIOS trial is designed to collect long-term safety information.^[2][1] Detailed side effect information would come from the published results of these studies.