Bitopertin reduces toxic metabolite PPIX in Phase 2 AURORA trial

PPIX levels drop in EPP patients on bitopertin vs increase seen in placebo group

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
Hands and a stethoscope frame a line graph labelled clinical trial.

The Phase 2 AURORA clinical trial has met its main goal, demonstrating that treatment with the experimental oral medication bitopertin reduced the levels of protoporphyrin IX in people with erythropoietic protoporphyria (EPP).

In EPP, disease symptoms are driven by the toxic buildup of protoporphyrin IX (abbreviated PPIX). Consistent with the reduction in PPIX levels, data from AURORA also indicate that treatment with bitopertin seems to reduce pain from sun exposure and improved patients’ overall sense of disease severity.

Top-line results from the Phase 2 study were announced by bitopertin’s developer, Disc Medicine.

“This study has confirmed that bitopertin significantly reduces the toxic metabolite, PPIX, in patients with EPP, and we have shown that bitopertin-treated patients experience improvements in the clinically meaningful outcomes,” John Quisel, PhD, Disc’s president and CEO, said in a company press release.

Recommended Reading
The words

Bitopertin seen to boost sunlight tolerance, life quality in patients

AURORA trial enrolled 75 adults with EPP

The AURORA trial (NCT05308472) enrolled 75 adults with EPP. Roughly half of the participants were female, and the average age was in the mid-40s.

Participants were given bitopertin at one of two doses (20 or 60 mg), or a placebo, daily for about four months (17 weeks).

The trial’s main goal was to assess the effect of bitopertin on PPIX levels. Like other types of porphyria, EPP is marked by deficiencies in the production of heme, leading to the toxic buildup of intermediates such as PPIX. Bitopertin is thought to regulate heme production by limiting the amount of glycine, a molecule needed to make heme, that can get into blood cells.

Results from AURORA showed PPIX levels decreased by 21.6% on average in patients given the lower dose of bitopertin, and by 40.7% in patients given the higher dose of the therapy. By comparison, in patients given the placebo, average PPIX levels increased by 8% over the course of the study.

BEACON trial: Bitopertin increased time that patients could spend in the sun

These AURORA results come a few months after Disc announced findings from another study called BEACON (ACTRN12622000799752). Data from BEACON indicated treatment with bitopertin increased the time adults with EPP could spend in the sun, though notably the study did not include a placebo group.

Over the course of AURORA, the average amount of time spent in sunlight on days without pain was 175.1 hours in the low-dose bitopertin group and 153.1 hours in the high-dose therapy group. These findings are in line with the benefits of treatment reported in BEACON, according to Disc.

However, patients given the placebo in AURORA also spent a significant amount of time in the sun over the course of the study — 133.9 hours, on average — and the difference between patients given the experimental therapy or the placebo was not statistically significant, meaning it’s mathematically plausible the difference could be due to random chance.

The average time to prodrome, or the time patients could spend in sunlight before beginning to experience symptoms, was also not significantly different between patients given bitopertin or the placebo. However, rates of painful reactions to light were significantly lower with the experimental therapy than the placebo, with a 60.3% reduction at the lower dose and 75.3% at the higher dose.

Recommended Reading
Main banner for

The benefits of finding experts in the field of the porphyrias

Fewer patients on bitopertin report painful reactions to sunlight

The total number of patients who experienced painful reactions to sunlight was also notably lower with bitopertin (19% at the low dose and 12% at the high dose) than in the placebo group (46%).

At the end of the trial, participants were asked to rate how their EPP severity had changed overall over the course of the study. About half of the patients given the placebo said their EPP was “much better.” In patients given bitopertin at either dose, more than three-quarters reported their disease was “much better.” A statistically significant difference was observed between the placebo and the higher dose group.

Safety data showed bitopertin was generally well tolerated, and the most common side effect of the therapy was dizziness. No serious side effects were reported in patients given the therapy, though two patients given the higher dose elected to quit the trial early due to side effects (dizziness in one patient and skin rash in the other).

Overall, the findings are promising, though due to the placebo group’s high response seen in measures of sunlight tolerance, the company is giving careful consideration on how to design future studies of bitopertin in EPP.

“We will need to conduct an analysis of our final data set and work with investigators, regulators, and patient advocacy groups to define the optimal registrational endpoints moving forward,” Quisel said.