What Is LY4584180?
LY4584180 is an investigational drug currently under study for the treatment of several types of lymphoma. The specific way LY4584180 works within the body is not detailed in the available trial descriptions, but it is known to be administered orally. This medication is being developed by Eli Lilly and Company. It is being investigated as a potential new therapy for serious blood cancers, including Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, and Non-Hodgkin's Lymphoma.
As an investigational drug, LY4584180 has not yet received approval from regulatory bodies such as the FDA. Its development is focused on exploring its safety and effectiveness in clinical trials. A single clinical trial has been initiated for LY4584180, which began on 2025-11-12 and aims to enroll a total of 360 participants. This trial is exploring different dosing strategies and combinations to determine the most effective approach for treating these lymphomas.
Uses and Conditions Under Study
LY4584180 is currently being investigated in clinical trials for the treatment of various types of lymphoma. Lymphomas are cancers that begin in infection-fighting cells of the immune system, called lymphocytes. These cancers can affect different parts of the body, including the lymph nodes, spleen, bone marrow, and other organs.
Specifically, LY4584180 is being studied for:
- Follicular Lymphoma: This is a slow-growing (indolent) type of non-Hodgkin's lymphoma that arises from B-lymphocytes. It is one of the most common types of non-Hodgkin's lymphoma. The single clinical trial for LY4584180 includes patients with Follicular Lymphoma.
- Diffuse Large B-Cell Lymphoma (DLBCL): This is an aggressive, fast-growing type of non-Hodgkin's lymphoma. It is the most common type of non-Hodgkin's lymphoma overall. LY4584180 is also being investigated in this patient population within the same trial.
- Non-Hodgkin's Lymphoma: This is a broad category of cancers that start in lymphocytes. Both Follicular Lymphoma and DLBCL fall under this umbrella. The trial is designed to assess the drug's effectiveness across this spectrum of conditions.
The single clinical trial, sponsored by Eli Lilly and Company, is exploring LY4584180 as a potential new treatment option for patients with these challenging blood cancers. The goal is to determine if LY4584180 can safely and effectively manage or improve outcomes for individuals diagnosed with these forms of lymphoma.
Dosing
LY4584180 is an investigational drug that is administered orally. The specific dosage strengths and frequency of administration are currently being determined in clinical trials. As part of its development, different dosing strategies are being evaluated to find the most effective and safest approach for patients with lymphoma.
The ongoing clinical trial for LY4584180 includes several phases of dose exploration:
- Phase 1a-Monotherapy Dose Escalation (Cohort A1): This initial phase involves gradually increasing doses of LY4584180 when given alone, to identify a safe and tolerable dose range.
- Phase 1a-Optional Monotherapy Dose Optimization (Cohort A2): Following dose escalation, this cohort may further refine the optimal dose when LY4584180 is used as a single agent.
- Phase 1b-Dose Expansion-Monotherapy (Cohorts B1-B4): In this phase, the drug is given as a monotherapy at selected doses to a larger group of patients to gather more data on its effectiveness and safety.
- Phase 1b-Dose Expansion-Combination (Cohort B5): This cohort explores LY4584180 in combination with other treatments, aiming to assess its potential benefits when used alongside existing therapies.
Since LY4584180 is still in clinical development, there is no standard adult dose established, nor are there specific pediatric doses being studied at this time. All dosing information is investigational and subject to change based on trial results.
Side Effects
The most common side effect reported in patients taking LY4584180 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a clinical trial, 18.2% of patients taking LY4584180 experienced diarrhea, compared to 4.7% of patients on placebo. Other common side effects in IBS-C patients included:
- Nausea: 5.2% of patients on LY4584180 vs. 2.3% on placebo.
- Abdominal pain: 4.2% of patients on LY4584180 vs. 2.0% on placebo.
- Vomiting: 3.3% of patients on LY4584180 vs. 1.3% on placebo.
- Upper respiratory tract infection: 2.6% of patients on LY4584180 vs. 2.0% on placebo.
- Headache: 2.3% of patients on LY4584180 vs. 2.0% on placebo.
In a separate study involving patients with hyperphosphatemia on dialysis, specific side effects were observed. Hyperkalemia (high potassium levels), AV fistula complication, and hypotension (low blood pressure) were each reported in 1.7% of patients taking LY4584180, compared to 0.0% of patients on placebo. In an open-label extension of this trial where no placebo was used for comparison, constipation, hypokalemia (low potassium levels), nausea, vomiting, and diarrhea were each reported in 1.7% of patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 2b clinical trial (NCT05047466) evaluated LY4584180 in 607 adult patients with IBS-C. Patients were randomly assigned to receive LY4584180 or a placebo. The primary goal was to determine the percentage of "Overall Responders," defined as patients who experienced both a complete spontaneous bowel movement (CSBM) response and an abdominal pain (AP) response in the same week for at least 6 of 12 treatment weeks. Results showed that 44% of patients on LY4584180 met this primary endpoint, compared to 33% of patients on placebo, representing a statistically significant difference of 11.1%.
Key secondary endpoints also demonstrated the effectiveness of LY4584180:
- CSBM Responder: 50% of patients on LY4584180 were CSBM responders (at least 3 CSBMs per week with an increase of at least 1 CSBM from baseline for at least 9 of 12 weeks), compared to 36% on placebo. This was a 13.8% difference.
- Abdominal Pain Responder: 51% of patients on LY4584180 were AP responders (at least 30% reduction from baseline in weekly average daily AP score for at least 9 of 12 weeks), compared to 42% on placebo. This was a 9.3% difference.
Patients taking LY4584180 also experienced an average increase of 2.6 complete spontaneous bowel movements per week, compared to an increase of 1.6 for those on placebo.
Hyperphosphatemia in Patients on Dialysis
A Phase 2 clinical trial (NCT05373678) investigated LY4584180 in 59 patients with hyperphosphatemia who were undergoing dialysis. The study aimed to assess the change in serum phosphorus levels from baseline to Week 4. A reduction in serum phosphorus indicates an improvement in hyperphosphatemia.
Results showed that patients receiving LY4584180 experienced a mean reduction in serum phosphorus of 1.0 mg/dL, while those on placebo had a mean reduction of 0.2 mg/dL. This resulted in a statistically significant difference of 0.8 mg/dL between the two groups.
Additionally, a greater proportion of patients treated with LY4584180 achieved target serum phosphorus levels:
- 55% of patients on LY4584180 achieved serum phosphorus levels below 4.5 mg/dL at Week 4, compared to 20% on placebo.
- 76% of patients on LY4584180 achieved serum phosphorus levels below 5.5 mg/dL at Week 4, compared to 43% on placebo.