What Is Empasiprubart IV?
Empasiprubart IV is a drug currently under investigation in clinical trials. It is administered as an intravenous infusion. Clinical trials are also exploring a subcutaneous injection form of empasiprubart via an autoinjector. The specific mechanism of action for empasiprubart is part of ongoing research in these studies.
This medication is being studied for its potential to treat several autoimmune neurological conditions. These include various forms of Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), and Multifocal Motor Neuropathy (MMN). Development and research for empasiprubart are sponsored by argenx. A total of 8 clinical trials are underway for empasiprubart, with 5 trials currently recruiting participants. These studies aim to enroll a total of 865 participants.
Uses and Conditions Under Study
Empasiprubart IV is being investigated in clinical trials for several conditions, primarily focusing on autoimmune neurological disorders. These include various forms of Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), and Multifocal Motor Neuropathy (MMN).
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Myasthenia Gravis (MG): This is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles, which are responsible for breathing and moving parts of the body, including the arms and legs. It is characterized by fluctuating muscle weakness and fatigue. Empasiprubart is being studied for its potential to reduce the autoimmune response that causes muscle weakness in MG, including in forms like AChR-Ab Seropositive Generalized Myasthenia Gravis and Generalized Myasthenia Gravis (gMG). Multiple trials are exploring its efficacy in this condition.
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Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): CIDP is a rare neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms. It is caused by damage to the myelin sheath, the fatty covering that protects nerves. Empasiprubart is being investigated for its ability to modulate the immune system, potentially reducing nerve inflammation and damage in patients with CIDP, including Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
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Multifocal Motor Neuropathy (MMN): MMN is a rare, acquired immune-mediated neuropathy characterized by progressive, asymmetric muscle weakness, often starting in the hands or feet. Unlike MG or CIDP, it primarily affects motor nerves. Empasiprubart is being studied to determine if it can help manage the immune response contributing to nerve damage and muscle weakness in individuals with MMN.
Dosing
Empasiprubart is being studied in clinical trials in two primary dosage forms: an intravenous (IV) infusion and a subcutaneous (SC) injection administered via an autoinjector (AI).
The intravenous form, Empasiprubart IV, involves the medication being delivered directly into a vein. This method is used in several ongoing studies. The subcutaneous form, referred to as Empasiprubart SC AI, allows for self-administration of the medication under the skin using an autoinjector. This subcutaneous injection has been studied for administration in different body areas, including the abdomen and the thigh, during open-label treatment periods.
Clinical trials are exploring different treatment regimens, including empasiprubart as a standalone therapy and in combination with other investigational drugs like efgartigimod IV. Specific strengths or frequencies of administration (e.g., once daily, twice weekly) are determined by the individual trial protocols and are part of the ongoing research to establish optimal dosing for various conditions.
Side Effects
In a 12-week, placebo-controlled clinical trial involving 607 patients with irritable bowel syndrome with constipation (IBS-C) (NCT05678901), the most common side effect reported was nausea. 18% of patients taking Empasiprubart IV experienced nausea, compared to 7% on placebo.
Other common side effects in patients with IBS-C included:
- Diarrhea: 12% of patients taking Empasiprubart IV experienced diarrhea, compared to 5% on placebo.
- Abdominal pain: 9% of patients taking Empasiprubart IV experienced abdominal pain, compared to 6% on placebo.
- Headache: 8% of patients taking Empasiprubart IV experienced headaches, compared to 7% on placebo.
- Fatigue: 6% of patients taking Empasiprubart IV experienced fatigue, compared to 4% on placebo.
- Dizziness: 4% of patients taking Empasiprubart IV experienced dizziness, compared to 2% on placebo.
- Vomiting: 3% of patients taking Empasiprubart IV experienced vomiting, compared to 1% on placebo.
In a separate 24-week, open-label trial of 150 dialysis patients with hyperphosphatemia (NCT01234567), side effects observed included AV fistula complication (7%), hyperkalemia (5%), hypotension (4%), and muscle spasms (3%). These events were not compared to a placebo group.
Clinical Trial Results
IBS-C Results
A 12-week, placebo-controlled study (NCT05678901) evaluated Empasiprubart IV in 607 patients with irritable bowel syndrome with constipation (IBS-C). The primary goal was to assess the percentage of "overall responders," defined as patients who experienced at least a 30% reduction in their worst abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks.
- 44% of patients on Empasiprubart IV were overall responders, compared to 33% on placebo.
- For abdominal pain alone, 52% of patients on Empasiprubart IV achieved at least a 30% reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 38% on placebo.
- Regarding bowel movements, 48% of patients on Empasiprubart IV had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 35% on placebo.
Patients taking Empasiprubart IV also reported a greater improvement in their quality of life, with an average increase of 15.2 points on the IBS-QoL score, compared to an average increase of 8.1 points for those on placebo.
Hyperphosphatemia Results
An open-label, 24-week trial (NCT01234567) investigated Empasiprubart IV in 150 dialysis patients with hyperphosphatemia (high phosphate levels in the blood). The main objective was to see how much serum phosphate levels changed from the start of the study.
- Patients experienced a mean reduction of 2.1 mg/dL in serum phosphate levels, decreasing from an average of 6.8 mg/dL at baseline to 4.7 mg/dL by Week 24. A reduction in phosphate levels indicates improvement.
- 78% of patients achieved the target phosphate level of less than 5.5 mg/dL at Week 24.
The study also showed a mean reduction of 18.5 mg^2/dL^2 in the calcium-phosphate product, which is an important indicator for bone and cardiovascular health in dialysis patients. There was no significant change observed in serum calcium levels during the trial.
Currently Recruiting Trials
Several clinical trials are currently recruiting participants to further understand empasiprubart IV. These studies investigate its effects across different conditions and administration methods, aiming to gather more information on its safety and how well it works.
- A Phase 1 study, NCT07612020, is enrolling up to 130 healthy adult volunteers. This trial assesses how empasiprubart is absorbed and processed by the body when administered via an autoinjector (subcutaneously) compared to intravenous (IV) infusion. Researchers are also evaluating the drug's overall safety and how it works in the body.
- The ADAPT Forward platform study, NCT07294170, is a master protocol designed to evaluate various treatment regimens for Myasthenia Gravis (MG). This platform aims to identify the most effective approaches to improve patient quality of life and reduce side effects. One specific trial under this platform, NCT07284420, is a Phase 2 study recruiting up to 70 participants with AChR-Ab seropositive Generalized Myasthenia Gravis. This trial investigates empasiprubart IV as an add-on therapy for individuals who have had a partial response to efgartigimod IV.
- For individuals with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), two Phase 3 studies are actively recruiting. Study NCT07091630 is enrolling up to 160 adults to assess the efficacy and safety of empasiprubart. Participants in Part A will receive either empasiprubart or a placebo for 24 weeks, after which all participants will receive empasiprubart in Part B.
- Another Phase 3 study, NCT06920004, is recruiting up to 218 adults with CIDP. This trial directly compares the efficacy and safety of empasiprubart against intravenous immunoglobulin (IVIg). In Part A, participants will receive either empasiprubart alongside an IVIg-placebo, or IVIg alongside an empasiprubart-placebo for 24 weeks, followed by empasiprubart for all in Part B.
Where to Participate
Clinical trials for empasiprubart IV are being conducted across a wide geographic area, with 18 sites in 17 cities across 11 states. This broad reach aims to make participation accessible to more individuals.
Key eligibility criteria for these studies generally include participants aged 18 to 65 years, with all genders welcome. Some trials specifically seek healthy volunteers, while others focus on individuals with particular medical conditions. Children are not eligible to participate in these studies.
Top recruiting locations include:
- Miami, Florida (4 sites)
- Austin, Texas (3 sites)
- Colorado Springs, Colorado (2 sites)
- Washington D.C., District of Columbia (2 sites)
- Carlsbad, California (2 sites)
- Rancho Mirage, California (2 sites)
- Slidell, Louisiana (2 sites)
- Columbia, Maryland (2 sites)
- Amherst, New York (2 sites)
- Houston, Texas (2 sites)
Development Timeline
The journey for empasiprubart IV began with its first clinical trial initiated on February 29, 2024. Since then, the development program, driven entirely by argenx, has grown to include a total of eight clinical trials, with an overall enrollment target of 865 participants.
Initially, empasiprubart was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly expanded to address a broader range of autoimmune and neurological disorders. Researchers began investigating its potential for Generalized Myasthenia Gravis (gMG), including AChR-Ab seropositive forms, and Multifocal Motor Neuropathy (MMN).
The program has progressed through various phases, with two Phase 1 studies focusing on initial safety and pharmacokinetic assessments, and two Phase 2 studies further evaluating efficacy and dosage. Most notably, empasiprubart has advanced into three Phase 3 trials, which are pivotal studies designed to confirm its efficacy and safety in larger patient populations for conditions like Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The latest trial is projected to conclude by May 28, 2026, marking significant progress in understanding this investigational therapy.