Disc Medicine’s bitopertin—rejected by the FDA in February—significantly reduced levels of a key disease biomarker and significantly increased the time patients with erythropoietic protoporphyria were able to spend in the sun and artificial light.
Disc Medicine’s bitopertin helped patients with a rare blood disorder that causes painful sensitivity to the sun spend more time in the light during a pivotal trial, setting the drug up for another attempt at an FDA approval after an accelerated application was rejected last year.
When the results were unblinded “a few days ago,” Disc CEO John Quisel was “overjoyed, as was our whole team,” he told BioSpace in an interview. “Just thrilled to be able to deliver a set of clean results in a set of endpoints that can be tricky.” The results, announced on Monday, revealed that the Phase 3 APOLLO trial hit all primary and secondary endpoints.
Prior to the results, analysts from BMO Capital Markets were optimistic that the readout could clear the way for a regulatory approval in erythropoietic protoporphyria (EPP). Senior Biopharma Analyst Evan Seigerman told BioSpace that the firm believed there was a high probability that APOLLO would deliver.
Seigerman said bitopertin’s established ability to lower PPIX and the APOLLO trial’s sunlight-exposure endpoint could give Disc a clear path back to regulators. Pivotal rare disease trials are designed to show clear clinical benefit, Seigerman explained. “If that trial hits, then there’s a real path forward for approval.”
The regulatory road for bitopertin to this point has been tricky. In its complete response letter (CRL), revealed in a February 13 SEC filing by Disc, the FDA questioned the biotech’s use of a surrogate endpoint—percent change in whole-blood metal-free protoporphyrin IX (PPIX), the toxic metabolite that drives the disease—as a reasonable predictor of clinical benefit in EPP.
“The percent change in PPIX was relatively modest,” the agency wrote in the CRL, noting that it is unknown whether such magnitude of biomarker effect “is reasonably likely to predict clinical benefit.”
Bitopertin was one of the first recipients of the Commissioner’s National Priority Voucher in October 2025, granted to products that align with certain national priorities, such as meeting a large unmet medical need or boosting domestic manufacturing. A CNPV entitles the product to a drastically shortened review period of one to two months, down from the typical 10–12 months—but it does not guarantee approval.
In June, Disc announced it had reached an agreement with the FDA whereby the regulator would allow the use of the ongoing APOLLO trial, if successful, to support another regulatory filing for bitopertin. With the new data in hand, Disc plans to resubmit its application—this time for traditional approval of bitopertin—to the FDA by end of the year.
Bitopertin soars in Phase 3
The APOLLO trial, which enrolled 183 adults and adolescents with EPP, showed that bitopertin reduced PPIX by 41.4% compared to placebo (p-value < 0.0001) and increased time patients were able to spend in the light by 12.2 hours during month six (p-value = 0.0010), meeting the study’s two co-primary endpoints with what Quisel called a “high” degree of statistical significance.
All secondary endpoints were also positive, Disc said, including a statistically significant reduction in phototoxic reactions—which Quisel described as “horrifically painful” attacks where the skin is damaged—and increased light tolerance. Exploratory measures of quality-of-life improvement were also statistically significant.
As to the pain attacks, Quisel elaborated on the experience patients have relayed to Disc. “What patients tell us is it feels like they’re being burned or cooked from the inside, because this chemical, PPIX, is floating around in their blood, and when it’s activated by the light, it literally is burning them from the inside.” Many patients receive opioids, even though they don’t address the pain effectively, he added.
Bitopertin was generally well-tolerated with no new safety signals observed in APOLLO, according to Disc’s press release. Dizziness was the most common treatment-emergent adverse event, with 50% of patients in the treatment group experiencing this side effect, but the cases were mild to moderate and generally transient, the company said.
In addition, there were no study discontinuations in the bitopertin arm of the study, “which is remarkable for a six-month study,” Quisel said.
Collectively, the results will support a fresh new drug application for bitopertin. When that filing reaches the FDA, it will face a regulator that looks quite different than it did in February. Former Commissioner Marty Makary, Center for Biologics Evaluation and Research (CBER) director Vinay Prasad and Center for Drug Evaluation and Research (CDER) Acting Director Tracy Beth Høeg have all departed the agency. Prasad reportedly intervened in the initial review of bitopertin, expressing his skepticism about the drug’s efficacy.
If Disc’s drug is cleared for the market, it will join Clinuvel Pharmaceuticals’ Scenesse, a subcutaneous implant that is the only treatment approved for EPP and to prevent phototoxic reactions.
Disc began development of bitopertin in 2021 when the company gained global rights to the asset from Roche. At the time, Disc paid an undisclosed upfront fee for the candidate and offered Roche more than $200 million in potential milestone payments.
Still to come
Beyond bitopertin, BMO is bullish on Disc because of the company’s two other clinical assets.
One of those is a monoclonal antibody called DISC-3405, designed to increase the production of hepcidin—a key regulator of iron entry into circulation—to therapeutically reduce iron levels. The drug, licensed from Mabwell Therapeutics in 2023, is being studied in a Phase 2 trial for polycythemia vera (PV) and a Phase 1b study for sickle cell disease.
In early September, Disc said that DISC-3405 increased hepcidin and lowered serum iron in patients with PV, translating to reduced blood draws and symptom burden, according to a poster presentation at the 2026 Society of Hematologic Oncology meeting.
Disc’s other asset is a monoclonal antibody called DISC-0974 picked up from AbbVie upon the biotech’s launch in 2019. Earlier this year, Disc shared that the asset reduced hepcidin and increased iron levels for patients with myelofibrosis (MF) and anemia in a Phase 2 trial called RALLY-MF.
Additional data from RALLY-MF are slated to read out sometime this quarter and are expected to “further clarify the asset’s differentiated profile in myelofibrosis anemia, with end of Phase 2 discussions with FDA providing more details on future Ph 3 trial design,” according to a September report from BMO.
As for bitopertin, Disc said in its press release that an FDA decision is expected by mid-2027. Asked if, given the previous allocation of a CNPV, the agency might move faster than the six months typical for a resubmission, Quisel said it’s possible. “They have a lot of priorities, so we will certainly ask, and we’ll see what we get.”
