BEACON, AURORA trials of bitopertin complete enrollment
Updated interim data will be presented during a December conference
The BEACON and AURORA Phase 2 clinical trials testing the investigational oral therapy bitopertin in people with erythropoietic porphyrias have completed enrollment, according to an update from therapy developer Disc Medicine.
BEACON (ACTRN12622000799752), which began enrolling adults with erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) at sites in Australia last year, has been expanded to include adolescent patients ages 12-18. All participants are receiving the therapy candidate.
Updated interim data from all patients will be presented at the 65th American Society of Hematology Annual Meeting and Exposition, being held Dec. 9-12 in San Diego and online.
Top-line data from the placebo-controlled AURORA trial (NCT05308472), involving adults with EPP, are expected to be presented in early 2024.
“We made tremendous progress this quarter … including a major milestone of completing enrollment of both BEACON and AURORA studies within a year,” John Quisel, PhD, president and CEO at Disc, said in a company press release. “We’re looking forward to the ASH 2023 meeting in December.”
As with all forms of porphyria, EPP and XLP are caused by mutations in genes needed to produce heme — a molecule important for oxygen transport in the body — leading to the toxic buildup of heme precursors. One called protoporphyrin IX (PPIX) accumulates in EPP and XLP.
Patients experience symptoms of extreme sunlight sensitivity with painful skin reactions upon exposure, as well as susceptibility to certain liver diseases.
Bitopertin works by blocking glycine transporter 1 (GlyT1), a protein that provides glycine, a molecule needed for heme production, to red blood cells. The company expects that by limiting glycine availability, bitopertin will help to regulate heme production and minimize PPIX accumulation in EPP and XLP.
Originally developed by Roche for schizophrenia, the oral therapy was acquired by Disc in 2021.
With BEACON study, patients take 20 mg or 60 mg of bitopertin
In BEACON, participants are randomly assigned to receive 20 mg or 60 mg of bitopertin, taken once per day for 24 weeks, or about six months. All could then opt to continue treatment at the 60 mg dose for an additional 24 weeks.
Interim trial analyses from 15 adult participants indicated that up to six months of bitopertin treatment was well tolerated, reduced PPIX levels by more than 40%, eased sunlight sensitivity, and improved life quality.
Updated data to be presented at the upcoming conference will concern all enrolled participants and a longer follow-up time, according to Disc.
According to the accepted abstract, the reported therapy’s benefits in the earlier interim analysis have generally been maintained across 17 adult participants enrolled as of a cut-off date of July 5.
Specifically, blood PPIX levels decreased by a mean of 39% from the study’s start to day 43 among patients with evaluable data, with more pronounced decreases in the 60 mg group.
The proportion of sunlight exposures without early symptoms of a pain attack increased from 2% pretrial to 49% while on bitopertin. Likewise, the number of sun-exposed days without symptoms increased from 26% to 74%.
Patients’ time in sunlight increased
Increases in weekly total time in sunlight were consistently observed, with the greatest increases observed in participants who experienced at least a 30% reduction in PPIX levels.
For those patients, the total time spent in sunlight increased from a weekly average of 339 minutes (about 48 minutes per day) at study’s start to a maximum of 999 minutes (about 2.4 hours daily) after a mean of more than four months of treatment.
Patient-reported toxic reactions to sunlight overall decreased by 93% while on bitopertin.
By day 43, 15 of 16 patients reported their EPP was at least a little better and the same number reported their condition was mild or not at all severe. Based on available responses to the EPP Impact Questionnaire, a new patient-reported measure, most patients said their EPP had little or no impact on their life quality while on bitopertin.
As previously reported, the treatment was generally well tolerated, with no serious adverse events reported. The most common side effects, reported in more than one patient, were dizziness and headache.
At the conference, the presented data may be different from and more up to date than those in the abstract, which is published ahead of the meeting.
AURORA, with a planned enrollment of 75 adults with EPP, is being conducted at sites in the U.S. Participants are randomly assigned to receive daily either one of two doses of bitopertin or a placebo for 120 days, or about four months. This is followed by an optional open-label extension phase where all will receive bitopertin for up to eight more months.
The main goal is to evaluate changes in blood PPIX levels after 120 days, with secondary goals related to sunlight sensitivity and tolerability. The trial is expected to end by mid-2024.