FDA grants priority voucher for investigational EPP drug bitopertin
Review period for Disc Medicine's therapy could be significantly reduced
Disc Medicine has received a Commissioner’s National Priority Voucher from the U.S. Food and Drug Administration (FDA) following its submission of a new drug application seeking accelerated approval of bitopertin, an investigational oral small molecule being developed for the treatment of erythropoietic protoporphyria (EPP) in patients ages 12 and older.
This voucher grants the company enhanced communication with the FDA and the possibility of a shortened review period — from the typical 10 to 12 months to under two months.
“We are honored to have received this voucher, which underscores the potential impact of bitopertin and reinforces the immense need EPP patients have for a new therapy that may address the underlying cause of their disease,” John Quisel, PhD, Disc’s president and CEO, said in a company press release. “We are grateful to the FDA for implementing this innovative new voucher program and we look forward to working closely with the agency to bring bitopertin to patients as soon as possible. All of this would not be possible without collaboration from the EPP patient and caregiver community, and we thank them for their contributions.”
Bitopertin is designed to inhibit key protein
EPP is caused by mutations in the FECH gene, which provides instructions for an enzyme that speeds up the chemical reaction whereby iron is added to protoporphyrin IX (PPIX) to produce heme, a component of hemoglobin and other iron-containing proteins.
These mutations limit the amount of heme that can be produced. As a result, PPIX builds up to toxic levels in red blood cells, leaks into the bloodstream, and spreads to the skin and other tissues in the body, causing oversensitivity to sunlight and damage to the liver and the gallbladder.
Since no approved treatment addresses the cause of EPP, patients must take extreme measures to avoid sunlight, such as wearing protective clothing, covering windows, or going outside only at night. Children and adolescents, in particular, may feel isolated because they cannot participate in normal outdoor activities.
Bitopertin is designed to inhibit a protein called glycine transporter 1 (GlyT1). This protein helps move glycine, an amino acid, into developing red blood cells, where it is used to produce heme. By inhibiting GlyT1, bitopertin is expected to reduce the buildup of PPIX, easing symptoms of EPP. Amino acids are the building block of proteins.
Phase 3 trial currently recruiting patients
Earlier Phase 2 clinical data from BEACON (ACTRN12622000799752), AURORA (NCT05308472), and an ongoing Phase 2/3 open-label extension study called HELIOS (NCT05883748) showed that a daily dose of 20 mg or 60 mg of bitopertin reduced the levels of PPIX in adults and adolescents with EPP. It also increased the time patients could spend in the sun without pain.
This reduction was sustained during long-term treatment, especially in patients receiving 60 mg of bitopertin continuously. There were also reductions in markers of damage to the liver, as well as improvements in quality of life. Bitopertin was found to be safe and well tolerated for more than two years of use, with similar results in both adults and adolescents.
An ongoing, confirmatory Phase 3 clinical trial called APOLLO (NCT06910358) is still recruiting up to 150 patients, ages 12 and older, who have been diagnosed with EPP or X-linked protoporphyria, another type of porphyria, in more than a dozen locations in the U.S., Australia, and Canada.
Patients will be randomly assigned to receive either bitopertin or a placebo once daily for 24 weeks, or about six months. The goal is based on changes in the total time spent in the sunlight on days without pain. Researchers will also measure the levels of PPIX in the blood and monitor side effects over the 24 weeks.
Bitopertin has received orphan drug and rare pediatric disease designations in the U.S. These designations support the development of treatments for rare diseases by providing benefits such as fee reductions and longer market exclusivity, should treatments be approved.
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