bitopertin (RG1678) / Roche, Disc Medicine - LARVOL DELTA

A Role for Glycine Transporter-2 Inhibitors in Regulating Accumbal Dopamine Levels and Voluntary Alcohol Intake in Rats. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Overall, this study indicates that synaptic GlyRs are involved in regulating nAc DA levels and alcohol intake in rats, but probably to a lesser extent than extrasynaptic GlyRs. Further studies that specifically target GlyT2 in, for example, the nAc and septal regions and that utilize refined techniques for measuring synaptic glycine levels are warranted to better characterize the role of glycinergic innervation in the reward circuitry and for regulating alcohol intake."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Additional Safety and Efficacy Results from HELIOS: A Phase 2, Open-Label, Long-Term Extension Study of Bitopertin in Erythropoietic Protoporphyria (EADV 2026) - No abstract available

Clinical • P2 data • Genetic Disorders • Metabolic Disorders

Study Design and Baseline Characteristics of APOLLO: A Randomized, Double-Blind, Placebo-Controlled Confirmatory Trial of Bitopertin in Adults and Adolescents with Erythropoietic Protoporphyria or X-Linked Protoporphyria (EADV 2026) - No abstract available

Clinical • Genetic Disorders • Metabolic Disorders

Glycine Transporter 1 Inhibitor, Bitopertin, Changes Excitatory and Inhibitory Network Connectivity in Mouse Medial Prefrontal Cortex. (PubMed, Neuropharmacology) - "Together, we found that bitopertin chiefly impacts the inhibitory network, while minimally affecting PNs. This insight could aid the development of more effective therapies for cognitive dysfunctions caused by E/I imbalance."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Results from the first clinical trial of bitopertin for steroid-relapsed/refractory Diamond-Blackfan anemia. (PubMed, Blood Red Cells Iron) - P1/2 | "Additionally, based on model systems, dosing may have escalated too rapidly, missing a potential lower effective dose. Future studies will test slower dose escalation of bitopertin as a steroid-sparing agent for steroid-responsive DBA patients."

Journal • Anemia • Genetic Disorders • Hematological Disorders

GlyT1 inhibition enhances working memory in the mouse TUNL task and normalizes NMDA antagonist-induced network activity. (PubMed, Psychopharmacology (Berl)) - "In summary, the TUNL task is sensitive to both impairments and enhancements of working memory in mice, even in the absence of pharmacological impairment. These findings identify GlyT1 inhibition as a pharmacological strategy capable of improving working memory performance and normalizing NMDA receptor antagonist-induced network activity."

Journal • Preclinical • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Comment on 'An open-label phase II study of bitopertin in adults and adolescents with erythropoietic protoporphyria or X-linked protoporphyria'. (PubMed, Clin Exp Dermatol) - No abstract available

Journal • P2 data • Genetic Disorders • Metabolic Disorders

A role for glycine transporter 2-inhibitors in modulating levels of dopamine in the nucleus Accumbens (EAN 2026) - " The partial GlyT2-inhibitors NAGly (10 mg/kg i.p.) and Opiranserin (20 mg/kg i.p.), but not the full GlyT2-inhibitor Org 25543, slightly elevated accumbal DA levels, while no effects on extrasynaptic glycine levels were observed. The reversible GlyT1-inhibitor Bitopertin (10 mg/kg p.o.) produced a pronounced glycine and DA elevation but combined GlyT1- and GlyT2 inhibition did not yield any statistically significant additive effects... To conclude, this study indicates that GlyT2-expressing glycinergic neurons are involved in regulating nAc DA levels, albeit to a lesser extent than extrasynaptic GlyRs situated nearby GlyT1s. The extraspinal effects mediated by systemic treatment with GlyT2-inhibitors, i.e. involvement of the mesolimbic DA system, should be further explored."

Improving working memory in mice using pro-cognitive drugs in the trial unique non-matched to location task (CINP 2026) - " The muscarinic antagonist scopolamine impaired performance to chance levels, whereas the glycine transporter 1 inhibitor bitopertin significantly improved accuracy...Bitopertin also rescued deficits induced by the NMDA receptor antagonist MK-801. Furthermore, functional ultrasound imaging revealed that bitopertin prevented ketamine-induced alterations in cerebral blood volume within prefrontal, hippocampal, and thalamic regions. These findings establish the mouse TUNL task as a sensitive tool for detecting pharmacological modulation of working memory in both improvements and impairments. Bitopertin and donepezil show promise as cognitive enhancers, with bitopertin additionally counteracting NMDA receptor–mediated impairments."

Preclinical

ADDITIONAL SAFETY AND EFFICACY RESULTS FROM HELIOS: A PHASE 2, OPEN-LABEL, LONG-TERM EXTENSION STUDY OF BITOPERTIN IN ERYTHROPOIETIC PROTOPORPHYRIA (EHA 2026) - P2/3 | "Summary/Conclusion By reducing PPIX levels, bitopertin targets the underlying pathophysiology of EPP and XLP . Results from HELIOS include participants who have received bitopertin for over 2 .5 years and support longer-term efficacy and safety with bitopertin in adult and adolescent patients with EPP or XLP."

Clinical • P2 data • Genetic Disorders • Hepatology • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease

Bitopertin: HELIOS update poster (GlobeNewswire) - "Disc Medicine presents positive clinical updates at the 2026 European Hematology Association (EHA) Annual Meeting....HELIOS is an ongoing Phase 2, open-label, long-term extension trial that enrolled 86 adult and adolescent patients with EPP....Longer term treatment with bitopertin was associated with sustained reductions in the disease-causing toxin PPIX, with additional benefit for patients receiving the 60 mg dose continuously. Treatment with bitopertin was associated with sustained, significant improvement in average light tolerance and time to prodrome measures. Bitopertin exhibited a favorable longer-term safety profile with up to 2.5+ years of exposure and similar safety across adults and adolescents with EPP and XLP."

P2 data • Genetic Disorders • Metabolic Disorders • Rare Diseases

Disc Medicine…completed a Type A meeting with the U.S. Food and Drug Administration to discuss the Complete Response Letter for bitopertin in erythropoietic protoporphyria, according to a press release statement issued Monday. (Investing.com) - “The FDA agreed that the ongoing Phase 3 APOLLO study, if successful, can serve as the basis for responding to the Complete Response Letter and could potentially support a traditional approval. The company expects to submit its response to the Complete Response Letter by the end of 2026."

FDA event • Hematological Disorders

Restricting glycine uptake with bitopertin improves erythropoiesis in preclinical models of Diamond-Blackfan anemia. (PubMed, Blood Red Cells Iron) - "We reasoned that bitopertin might help balance heme synthesis with globin synthesis and improve erythropoiesis in patients with DBA. Our observations in samples from patients with DBA, CD34+ cells engineered to downregulate RPS19, and a murine DBA model support this concept, justify ongoing clinical studies, and provide insight into optimal trial design."

Journal • Preclinical • Anemia • Genetic Disorders • Hematological Disorders • CD34

Expanded Access Program of Bitopertin For Participants With EPP or XLP (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Disc Medicine, Inc

New trial • Genetic Disorders • Metabolic Disorders

HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP (clinicaltrials.gov) - P2/3 | N=230 | Enrolling by invitation | Sponsor: Disc Medicine, Inc | N=46 ➔ 230

Enrollment change • Genetic Disorders • Metabolic Disorders

Study of Bitopertin in Participants With EPP or XLP (APOLLO) (clinicaltrials.gov) - P3 | N=183 | Active, not recruiting | Sponsor: Disc Medicine, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Metabolic Disorders

GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "We further synthesize pharmacological advances in GlyT1 inhibition, evaluating both sarcosine-derived and non-sarcosine inhibitors, such as NFPS (ALX-5407), bitopertin, and iclepertin. The clinical and preclinical evidence for GlyT1 as a therapeutic target in psychiatric, neurological, and neurodegenerative disorders is critically assessed. Finally, we address key translational challenges, including dosing constraints, compensatory mechanisms, and SLC6 family selectivity, while highlighting the potential of structure-guided design to refine GlyT1-targeted therapies."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP (clinicaltrials.gov) - P2/3 | N=46 | Enrolling by invitation | Sponsor: Disc Medicine, Inc

New P2/3 trial • Genetic Disorders • Metabolic Disorders

A study to evaluate if Bitopertin is safe, well tolerated, and effective in patients with Erythropoietic Protoporphyria (EPP) including analyzing its effect on Protoporphyrin IX (PPIX) concentrations (clinicaltrialsregister.eu) - P2 | N=26 | Sponsor: Disc Medicine, Inc.

New P2 trial • Genetic Disorders • Metabolic Disorders

New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin. (PubMed, Expert Opin Pharmacother) - "However, safety and efficacy of dersimelagon and bitopertin need to be further characterized. Moreover, to ensure benefit for patients and access to therapy after regulatory approval, it also would be important to generate data on the relative safety and efficacy as compared to afamelanotide."

Journal • Review • Genetic Disorders • Metabolic Disorders • Pain • Rare Diseases

Disc Medicine Receives Complete Response Letter from FDA for Bitopertin for the Treatment of EPP (GlobeNewswire) - "FDA acknowledged that AURORA and BEACON provided sufficient evidence that bitopertin significantly lowers PPIX and that there is a strong mechanistic and biological plausibility supporting the use of the PPIX biomarker in protoporphyria. FDA indicated a need to see the results of the ongoing Phase 3 APOLLO study before making a decision. Ongoing Phase 3 APOLLO study potential to serve as basis for traditional approval; topline data anticipated Q4 2026....Upon completion of APOLLO, Disc would then file a response to the CRL and expect an updated FDA decision by mid-2027."

CRL • FDA approval • P3 data: top line • Hematological Disorders

DISC-1459-301: APOLLO: A Randomized, Double-Blind, Placebo-Controlled Study of Bitopertin to Evaluate the Efficacy, Safety, and Tolerability in Participants with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) (clinicaltrialsregister.eu) - P2/3 | N=71 | Recruiting | Sponsor: Disc Medicine Inc.

New P2/3 trial • Genetic Disorders • Metabolic Disorders

DISC-1459-501: HELIOS: Long-term study of DISC-1459 (or Bitopertin) in patients with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP). (clinicaltrialsregister.eu) - P2/3 | N=32 | Not yet recruiting | Sponsor: Disc Medicine Inc.

New P2/3 trial • Genetic Disorders • Metabolic Disorders

DISC-1459-301: APOLLO: A Randomized, Double-Blind, Placebo-Controlled Study of Bitopertin to Evaluate the Efficacy, Safety, and Tolerability in Participants with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) (clinicaltrialsregister.eu) - P2/3 | N=56 | Recruiting | Sponsor: Disc Medicine Inc.

New P2/3 trial • Genetic Disorders • Metabolic Disorders

Effect of Bitopertin on the Liver and on Levels of Protoporphyrin IX in Bile, Blood, Liver, and Stool in Patients With Erythropoietic Protoporphyria/X-linked Protoporphyria and Increased Liver Stiffness and/or Liver Enzymes at Baseline (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Wake Forest University Health Sciences | N=10 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders • Metabolic Disorders