Priority Review Requested for Rare Disease Therapy Bitopertin

Disc Medicine has submitted a New Drug Application (NDA) to the US FDA for bitopertin, an investigational oral therapy for erythropoietic protoporphyria (EPP), including X-linked protoporphyria (XLP). The filing seeks approval for patients aged 12 years and older under the FDA’s accelerated approval pathway.¹

The application is supported by phase 2 clinical data and includes a request for Priority Review. If granted, this designation would shorten the FDA’s review goal from 10 months to 6 months after the 60-day filing period. Bitopertin has already received both Orphan Drug and Rare Pediatric Disease designations, reflecting the significant unmet need in this patient population.

"This NDA submission is an exciting opportunity for the rare dermatologic disease space to see an impactful oral therapy, bitopertin, advance through the regulatory process to serve the EPP/porphyria patient community," Christopher Bunick, MD, PhD, associate professor of dermatology at the Yale School of Medicine and editor in chief of Dermatology Times said.

Supporting Data

The NDA is anchored by results from 2 key phase 2 studies, BEACON (ACTRN12622000799752) and AURORA (NCT05883748), as well as safety data collected in earlier studies conducted by Roche, which encompass more than 4,000 participants. In both trials, patients treated with bitopertin demonstrated significant reductions in protoporphyrin IX (PPIX) levels, a toxic, photoactive metabolite that underlies the pathology of EPP.

Lowering PPIX was associated with clinical improvements in light tolerance, reduction in phototoxic reactions, and overall quality of life benefits. Patients reported increased ability to perform outdoor activities without experiencing the excruciating pain and skin damage typically associated with sunlight exposure.

In addition to BEACON and AURORA, Disc is conducting the HELIOS open-label extension study to evaluate long-term safety and durability of response. In April 2025, the company also initiated the confirmatory phase 3 APOLLO trial, a double-blind, placebo-controlled study designed to further validate bitopertin’s clinical benefit.

Mechanism of Action

Bitopertin is an orally administered inhibitor of glycine transporter 1 (GlyT1). GlyT1 provides developing red blood cells with glycine, an essential substrate in heme biosynthesis. By modulating glycine uptake, bitopertin alters heme synthesis in a way that reduces accumulation of PPIX.

This mechanism represents a potentially disease-modifying approach for EPP, distinguishing bitopertin from the only currently approved treatment, afamelanotide (Scenesse; Clinuvel). Afamelanotide is a surgically implanted synthetic analog of alpha-melanocyte stimulating hormone that increases melanin production to provide partial photoprotection, but it does not directly address PPIX accumulation.

Disease Burden and Unmet Need

Erythropoietic protoporphyria (EPP) and its X-linked variant are rare, inherited metabolic disorders caused by mutations in heme biosynthetic enzymes. The resulting accumulation of PPIX in erythrocytes, plasma, and hepatocytes renders patients highly sensitive to visible light. Even brief sun exposure can trigger severe burning pain, edema, and, in some cases, blistering and scarring.²

Beyond cutaneous manifestations, PPIX accumulation can lead to hepatobiliary complications including gallstones, cholestasis, and progressive liver injury, with 20–30% of patients developing clinically significant hepatic disease and rare progression to liver failure.

Because of extreme photosensitivity, many patients adopt stringent protective behaviors, including daytime indoor confinement, use of UV-opaque clothing and shields, and avoidance of most outdoor activities. This restriction significantly impairs psychosocial development, school attendance, employment, and overall quality of life, particularly for children and young adults.

Current management strategies are limited. Aside from afamelanotide, supportive care remains the standard, focusing on light avoidance and symptomatic pain control. No therapies currently approved in the United States modify the underlying metabolic defect.

Regulatory Outlook

With its NDA submission, Disc Medicine seeks accelerated approval of bitopertin using PPIX reduction as a surrogate endpoint reasonably likely to predict clinical benefit. Should the FDA accept the filing and grant Priority Review, a regulatory decision could be expected within approximately 8 months.

While regulatory success is not assured, bitopertin’s clinical profile offers the potential to become the first oral, disease-modifying therapy for EPP. Its ability to reduce PPIX and improve light tolerance may represent a meaningful advance over current therapeutic approaches.

Clinical Implications

For dermatologists and hematologists managing patients with EPP, the availability of an oral therapy targeting the biochemical basis of the disease would represent a significant paradigm shift. By addressing the accumulation of PPIX, bitopertin may expand treatment options, improve patient autonomy, and reduce the psychosocial burden of strict photoprotection. Further results from the APOLLO confirmatory trial and long-term HELIOS study will be essential in defining the safety, durability, and real-world applicability of this investigational agent.

References

1. Disc Medicine announces submission of New Drug Application (NDA) to US FDA for accelerated approval of bitopertin for patients with erythropoietic protoporphyria (EPP). News release. Disc Medicine. Published September 30, 2025. Accessed October 2, 2025. https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-announces-submission-new-drug-application-nda-us
2. Minder AE, Kluijver LG, Barman-Aksözen J, Minder EI, Langendonk JG. Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management. Liver Int. 2025;45(1):e16027. doi:10.1111/liv.16027