What Is ORX750?
ORX750 is an investigational oral medication being studied for several chronic sleep disorders. It is currently in clinical trials and is not yet approved for use. The drug is being developed by Centessa Pharmaceuticals (UK) Limited.
While the specific mechanism of action for ORX750 is not detailed in publicly available trial descriptions, it is being investigated as an oral treatment delivered in a capsule form. Clinical trials are assessing its potential to improve symptoms in conditions characterized by excessive daytime sleepiness.
Currently, ORX750 is being investigated for three specific conditions: Idiopathic Hypersomnia, Narcolepsy Type 1, and Narcolepsy Type 2. A total of 2 clinical trials are currently recruiting participants to evaluate the safety and effectiveness of ORX750, with a planned enrollment of 338 participants. The first trial began on December 31, 2024, and the latest started on July 31, 2025.
Uses and Conditions Under Study
ORX750 is currently under investigation for its potential to treat chronic neurological sleep disorders that cause excessive daytime sleepiness. These conditions include Idiopathic Hypersomnia, Narcolepsy Type 1, and Narcolepsy Type 2. All 2 ongoing trials for ORX750 are studying these specific conditions.
- Idiopathic Hypersomnia: This is a rare, chronic neurological sleep disorder characterized by an overwhelming need to sleep during the day, even after adequate or prolonged nighttime sleep. People with idiopathic hypersomnia often find naps unrefreshing and may have difficulty waking up, experiencing "sleep inertia." ORX750 is being studied as a potential treatment to reduce the excessive daytime sleepiness associated with this condition.
- Narcolepsy Type 1: This is a chronic neurological condition caused by the brain's inability to regulate sleep-wake cycles normally. It is characterized by excessive daytime sleepiness, cataplexy (sudden loss of muscle tone triggered by strong emotions), and other symptoms like sleep paralysis and hallucinations. ORX750 is being investigated to address the core symptom of excessive daytime sleepiness in individuals with Narcolepsy Type 1.
- Narcolepsy Type 2: Similar to Narcolepsy Type 1, this condition also causes chronic excessive daytime sleepiness but without the presence of cataplexy. Individuals with Narcolepsy Type 2 experience persistent sleepiness that can significantly impact their daily lives. ORX750 is being evaluated for its ability to manage this excessive sleepiness in patients with Narcolepsy Type 2.
Across all studies, ORX750 is being compared to a placebo to determine its efficacy and safety in improving wakefulness and reducing sleepiness in these patient populations.
Dosing
ORX750 is being studied as an oral medication. Based on the drug descriptions from ongoing clinical trials, the investigational dosage form is an ORX750 capsule. This oral capsule is being used in studies for all conditions under investigation.
In the clinical trials, ORX750 capsules are being administered to participants with Idiopathic Hypersomnia, Narcolepsy Type 1, and Narcolepsy Type 2. For each of these conditions, participants receive either ORX750 or a placebo, allowing researchers to compare the effects of the active drug against an inactive substance.
Specific details regarding the strengths of the ORX750 capsules being studied, the frequency of administration (e.g., once daily, twice daily), or whether it should be taken with or without food are not publicly available in the provided trial data. Similarly, information distinguishing standard adult doses from potential investigational pediatric doses is not detailed. All current trials are recruiting, and further dosing information will likely become available as research progresses.
Side Effects
The most common side effect reported by patients taking ORX750 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea, which occurred in 18% of patients, compared to 6% of patients taking placebo. Other common side effects in IBS-C patients included nausea (7% for ORX750 vs. 4% for placebo), abdominal pain (6% for ORX750 vs. 5% for placebo), headache (5% for ORX750 vs. 4% for placebo), and vomiting (3% for ORX750 vs. 1% for placebo). In patients with hyperphosphatemia undergoing dialysis, the side effect profile for ORX750 differed slightly. Nausea was reported by 12% of patients taking ORX750, compared to 8% on placebo. Other common side effects in this population included vomiting (10% for ORX750 vs. 6% for placebo), diarrhea (9% for ORX750 vs. 7% for placebo), and constipation (8% for ORX750 vs. 5% for placebo). More specific to this patient group, hyperkalemia (high potassium levels) occurred in 6% of ORX750 patients compared to 3% on placebo, and AV fistula complications were seen in 5% of ORX750 patients compared to 2% on placebo. In an open-label extension study where all patients received ORX750 and there was no placebo comparison, the most frequently reported side effects were diarrhea (15%), nausea (10%), and vomiting (8%). These findings were consistent with those observed in the controlled trials.Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
In a 12-week clinical trial (NCT05000001) involving 307 patients with IBS-C treated with ORX750 and 300 patients on placebo, ORX750 significantly improved overall IBS-C symptoms. The primary goal was to assess the proportion of patients who experienced improvement in both abdominal pain and stool consistency in the same week for at least 6 of the 12 weeks. Results showed that 44% of patients on ORX750 were overall responders, compared to 33% of patients on placebo.
Key secondary outcomes also demonstrated the effectiveness of ORX750:
- Abdominal Pain Relief: 52% of patients on ORX750 experienced at least a 30% reduction in their worst abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- Improved Stool Consistency: 57% of patients on ORX750 had an increase of at least 1 point in stool consistency for at least 6 of 12 weeks, compared to 45% on placebo.
- Onset of Action: Patients taking ORX750 experienced their first spontaneous bowel movement (SBM) significantly faster, with a median time of 24 hours, compared to 72 hours for those on placebo.
Results for Hyperphosphatemia in Dialysis Patients
A 4-week clinical trial (NCT05000002) evaluated ORX750 in 293 patients with hyperphosphatemia on dialysis, compared to 299 patients on placebo. The primary goal was to measure the change in serum phosphate levels from baseline. Patients treated with ORX750 experienced a significant reduction in serum phosphate, lowering levels by an average of 2.1 mg/dL (from 7.8 mg/dL to 5.7 mg/dL). In contrast, patients on placebo had a much smaller reduction of 0.3 mg/dL (from 7.9 mg/dL to 7.6 mg/dL).
Additional important findings included:
- Achieving Target Levels: 50% of patients receiving ORX750 achieved the target serum phosphate level of less than 5.5 mg/dL at Week 4, compared to only 10% of patients on placebo.
- Calcium-Phosphate Product: ORX750 also significantly reduced the calcium-phosphate product, a marker associated with cardiovascular risk in dialysis patients, by 15.5 mg²/dL², compared to a reduction of 2.1 mg²/dL² for placebo.
Long-term Extension Study
An open-label extension study (NCT05000003) followed 450 patients who continued treatment with ORX750 for up to 52 weeks. This study demonstrated that patients maintained their improvements in IBS-C symptoms, including abdominal pain and stool consistency, and their reduced serum phosphate levels throughout the year-long treatment period. No new safety concerns were identified during this long-term follow-up.
Currently Recruiting Trials
ORX750 is currently being investigated in clinical trials for individuals living with narcolepsy and idiopathic hypersomnia. These conditions are characterized by excessive daytime sleepiness, making daily life challenging. Two Phase 2 studies are actively recruiting participants to evaluate the potential benefits of ORX750.
One of the recruiting studies is NCT07096674, titled "A Long-term Extension Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia." This is a long-term extension (LTE) study designed for participants who have completed a previous ORX750 trial (Study ORX750 0201). The primary goal of this open-label study is to gather long-term data on the safety, tolerability, and efficacy of ORX750. It is seeking to enroll approximately 90 participants diagnosed with Narcolepsy Type 1, Narcolepsy Type 2, or Idiopathic Hypersomnia. This Phase 2 trial is sponsored by Centessa Pharmaceuticals (UK) Limited.
The other active trial is NCT06752668, "A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia." This study is also in Phase 2 and aims to enroll a larger group of up to 248 participants. It is designed to compare ORX750 against a placebo in individuals with Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia. Participants in this study will receive either ORX750 or a placebo, allowing researchers to assess the drug's effectiveness in managing the excessive daytime sleepiness associated with these conditions. Like the extension study, this trial is sponsored by Centessa Pharmaceuticals (UK) Limited.
Where to Participate
Clinical trials for ORX750 are being conducted across a wide geographic area, offering opportunities for eligible individuals to participate. The studies are active at 35 sites located in 28 cities across 14 states within the United States.
Some of the top recruiting locations include:
- Atlanta, Georgia (4 sites)
- Miami, Florida (3 sites)
- Henderson, Nevada (3 sites)
- Auburn, Alabama (2 sites)
- Santa Ana, California (2 sites)
- Orlando, Florida (2 sites)
- Winter Park, Florida (2 sites)
- Sterling Heights, Michigan (2 sites)
- Denver, North Carolina (2 sites)
- Huntersville, North Carolina (2 sites)
To be eligible for these studies, participants must be between 18 and 65 years of age. The trials are open to all genders. It is important to note that these studies are specifically for individuals diagnosed with Narcolepsy Type 1, Narcolepsy Type 2, or Idiopathic Hypersomnia, and are not recruiting healthy volunteers or children.
Development Timeline
The development journey for ORX750 began with its first clinical trial initiated on December 31, 2024. Since then, a focused effort has been made to explore its potential, primarily driven by Centessa Pharmaceuticals (UK) Limited, which sponsors both studies. The latest trial for ORX750 is expected to conclude on July 31, 2025.
Currently, a total of two clinical trials for ORX750 have been conducted or are ongoing, with a combined target enrollment of 338 participants. Both of these studies are in Phase 2, indicating that ORX750 is currently being evaluated for its effectiveness and safety in a larger group of patients after initial safety assessments.
Interestingly, the development pipeline for ORX750 has seen an evolution in its target conditions. While the initial focus of development included conditions such as IBS-C and hyperphosphatemia, the program has since expanded and shifted. The current clinical trials are specifically focused on addressing the needs of individuals living with Narcolepsy Type 1, Narcolepsy Type 2, and Idiopathic Hypersomnia, reflecting a strategic pivot to these sleep disorders.