Disc Medicine Gains FDA Alignment on Bitopertin Trial Design for Erythropoietic Protoporphyria
核心洞察
Disc Medicine's Type C meeting with the FDA resulted in alignment on the design of the APOLLO post-marketing confirmatory trial for bitopertin in EPP.
The APOLLO trial will assess bitopertin's efficacy using co-primary endpoints focusing on sunlight tolerance and PPIX reduction over a 6-month treatment period.
The FDA agreed to the potential for accelerated approval based on existing data and utilizing reduction of PPIX as a surrogate endpoint.
Disc Medicine (NASDAQ:IRON) has announced positive feedback from a Type C meeting with the U.S. Food and Drug Administration (FDA) regarding the APOLLO post-marketing confirmatory trial for bitopertin in patients with Erythropoietic Protoporphyria (搜索) (EPP), including X-linked protoporphyria (搜索) (XLP). The agreement with the FDA paves the way for a potential accelerated approval pathway for bitopertin, marking a significant step forward in addressing the unmet needs of EPP patients.
APOLLO Trial Design
The APOLLO trial, a randomized, double-blind, placebo-controlled study, is set to enroll approximately 150 patients aged 12 and older with EPP, including those with XLP. Participants will be randomized 1:1 to receive either a 60 mg dose of bitopertin or a placebo over a 6-month treatment duration. The trial design incorporates several key features agreed upon with the FDA:
- Co-primary endpoints: The trial will evaluate the average monthly total time in sunlight without pain between 10:00 and 18:00 during the last month of the 6-month treatment period, alongside the percent change from baseline in whole blood metal-free PPIX after 6 months of treatment.
- Secondary endpoints: Additional efficacy measures include the occurrence of phototoxic reactions, cumulative total pain-free time in sunlight, patient global impression of change, and time to prodrome.
Accelerated Approval Potential
Notably, the FDA has indicated the potential for accelerated approval of bitopertin based on existing data, with the reduction of protoporphyrin IX (PPIX) serving as a surrogate endpoint. This pathway could allow Disc Medicine to submit a New Drug Application (NDA) based on existing data, with the APOLLO trial acting as a confirmatory study. The company plans to meet with the FDA to finalize the details of the APOLLO trial and anticipates providing an update in Q1 2025 regarding the NDA filing timeline under the accelerated pathway.
Bitopertin: A Potential Disease-Modifying Therapy
Bitopertin is an investigational, orally administered inhibitor of glycine transporter 1 (GlyT1), designed to modulate heme biosynthesis. By inhibiting GlyT1, bitopertin aims to reduce the accumulation of PPIX, the toxic intermediate responsible for the debilitating photosensitivity experienced by EPP patients. Disc Medicine obtained global rights to bitopertin from Roche in May 2021 and is developing it as a potential first disease-modifying therapy for erythropoietic porphyrias.
Addressing Unmet Needs in EPP
Erythropoietic protoporphyria (搜索) (EPP) and X-linked Protoporphyria (搜索) (XLP) are rare genetic diseases characterized by mutations affecting heme biosynthesis, leading to the accumulation of PPIX. This accumulation results in severe, painful reactions upon exposure to sunlight, significantly impacting patients' quality of life. Current treatments primarily focus on managing symptoms and avoiding sunlight. The only FDA-approved therapy, Scenesse (afamelanotide), is a surgically implanted synthetic hormone designed to stimulate melanin production. Bitopertin represents a potential new approach by targeting the underlying cause of the disease.
Management Commentary
"We are thrilled with the outcome of our end-of-Phase 2 meeting with the FDA, which provides us with a clear development path forward for bitopertin," said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc Medicine. "Importantly, the FDA agreed with all attributes of our study design, including a primary endpoint we feel is statistically robust and would fully capture the potential benefit of bitopertin in EPP."