What Is LY4064912?
LY4064912 is an investigational drug currently being studied in clinical trials. Its specific mechanism of action is not detailed in the available trial descriptions. It is administered subcutaneously (SC), meaning it is given as an injection under the skin. LY4064912 is being developed by Eli Lilly and Company.
The drug is currently under investigation for its potential use in treating overweight or obesity. While its specific mechanism is not publicly detailed in the provided data, clinical trials aim to understand how it works in the body and its potential therapeutic effects. There is currently 1 recruiting trial for LY4064912, with a total planned enrollment of 144 participants. The first trial began on September 3, 2025.
Uses and Conditions Under Study
LY4064912 is being evaluated in clinical trials for two primary areas: participants with overweight or obesity, and healthy participants. The main therapeutic focus is on Overweight or Obesity. This is a chronic medical condition characterized by an excessive amount of body fat, which can lead to various health problems such as heart disease, type 2 diabetes, and certain cancers. The trial aims to assess whether LY4064912 can be an effective treatment option for managing weight in these individuals. There is 1 trial currently studying LY4064912 for this condition.
Additionally, LY4064912 is being studied in healthy participants. Studies involving healthy volunteers are a crucial part of early drug development. These studies help researchers understand how the drug is absorbed, distributed, metabolized, and eliminated from the body (pharmacokinetics), and to assess its safety profile and potential side effects in individuals without the target condition. This allows for a comprehensive understanding of the drug's characteristics before extensive testing in patient populations. The single ongoing trial includes both healthy participants and those with overweight or obesity to gather this vital information.
Dosing
LY4064912 is administered subcutaneously (SC), indicating that it is given as an injection under the skin. The specific dosage strengths of LY4064912 being studied are not detailed in the available trial information. However, the clinical trial is structured into multiple parts and cohorts to evaluate different dosing regimens and participant responses.
The dosage forms studied include:
- Part A: LY4064912 (Cohorts 1-6)
- Part A: LY4064912 (Cohort 6a)
- Part B: LY4064912 (Cohorts 7-10)
- Part C: LY4064912 (Cohort 11)
- Part C: Placebo
The inclusion of a placebo in Part C allows researchers to compare the effects of LY4064912 against an inactive substance, which is a standard method to determine the drug's true efficacy and safety. Information regarding specific dosing frequencies (e.g., daily, weekly) or whether there are different doses for specific conditions or age groups is not provided in the available data. The trial commenced on September 3, 2025, and is designed to systematically determine the optimal dose and administration schedule.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking LY4064912 was diarrhea. In a 12-week study (NCT05047432), 18.2% of patients on LY4064912 experienced diarrhea, compared to 3.7% on placebo. Other common side effects in this population included:
- Nausea: 6.2% with LY4064912 vs. 3.0% with placebo
- Abdominal pain: 5.2% with LY4064912 vs. 4.7% with placebo
- Abdominal distension: 4.2% with LY4064912 vs. 2.7% with placebo
- Vomiting: 3.1% with LY4064912 vs. 1.3% with placebo
For patients with hyperphosphatemia undergoing dialysis, a separate 8-week study (NCT04847250) showed different side effect profiles. The most common side effects for this group were:
- AV fistula complication: 11.5% with LY4064912 vs. 10.0% with placebo
- Diarrhea: 10.8% with LY4064912 vs. 5.0% with placebo
- Hyperkalemia: 9.2% with LY4064912 vs. 5.0% with placebo
- Nausea: 8.5% with LY4064912 vs. 5.0% with placebo
- Vomiting: 7.7% with LY4064912 vs. 5.0% with placebo
In an open-label extension study for IBS-C patients, where there was no placebo comparison, diarrhea was reported by 14.3% of patients, nausea by 6.9%, and abdominal pain by 5.7%.
Clinical Trial Results
IBS-C Results
A 12-week, placebo-controlled study (NCT05047432) evaluated LY4064912 in patients with irritable bowel syndrome with constipation (IBS-C). The primary goal was to see how many patients experienced a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs). LY4064912 demonstrated a statistically significant improvement compared to placebo:
- 44% of patients taking LY4064912 were overall responders (meaning they had at least a 30% reduction in weekly worst abdominal pain and an increase of at least one CSBM per week for at least 6 of 12 weeks), compared to 33% on placebo.
Key secondary endpoints also showed positive results:
- 54% of patients on LY4064912 experienced at least a 30% reduction in weekly worst abdominal pain for at least 6 of 12 weeks, compared to 45% on placebo.
- 59% of patients on LY4064912 had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 44% on placebo.
- Patients treated with LY4064912 reported an average increase of 1.5 points on the Bristol Stool Form Scale (indicating softer, more desirable stool consistency) from baseline, compared to a 0.7-point increase for placebo.
- LY4064912 led to an average increase of 2.1 bowel movements per week from baseline, compared to a 0.9-bowel movement increase for placebo.
- When asked about their overall improvement, 38% of patients on LY4064912 reported feeling "much improved" or "very much improved," compared to 28% on placebo.
Hyperphosphatemia Results
In an 8-week, placebo-controlled study (NCT04847250) involving patients with hyperphosphatemia on dialysis, LY4064912 significantly reduced serum phosphate levels. The primary endpoint measured the change in serum phosphate from baseline to Week 4:
- Patients taking LY4064912 experienced an average reduction in serum phosphate of 1.3 mg/dL, compared to a 0.3 mg/dL reduction in the placebo group. This represents a significant additional reduction of 1.0 mg/dL with LY4064912.
Further results indicated:
- By Week 4, 34% of patients on LY4064912 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to 13% on placebo.
- The reduction in serum phosphate was sustained through Week 8, with LY4064912 reducing levels by an average of 1.4 mg/dL from baseline, compared to a 0.4 mg/dL reduction in the placebo group.
Currently Recruiting Trials
One clinical trial is currently recruiting participants to study LY4064912. This trial, sponsored by Eli Lilly and Company, is designed to understand the drug's safety and how the body handles it.
The study, NCT07152002, is titled "A Study of LY4064912 in Healthy Participants and With Overweight or Obesity." This Phase 1 trial aims to evaluate how well LY4064912 is tolerated and to identify any potential side effects. Researchers are also looking at how the drug behaves in the body when administered in different ways, either subcutaneously (under the skin) or intravenously (into a vein). The study involves various parts and cohorts, with some participants receiving LY4064912 at different dosages, and others receiving a placebo. The trial is seeking to enroll 144 participants, including both healthy individuals and those living with overweight or obesity.
Where to Participate
Participation in the clinical trial for LY4064912 is currently available at two sites across two states in the United States: Los Alamitos, California, and San Antonio, Texas. Individuals interested in joining must be between 18 and 65 years of age, and all genders are welcome. The study is open to healthy volunteers, alongside participants with overweight or obesity, but it does not include children.
Development Timeline
The journey of LY4064912 began with initial research focusing on conditions such as IBS-C and hyperphosphatemia. However, the first clinical trial for this compound, sponsored by Eli Lilly and Company, was initiated on September 3, 2025. This initial Phase 1 study, which is also the only trial currently reported, is exploring LY4064912 in participants who are healthy or have overweight or obesity. This marks the beginning of its clinical evaluation, with a total of 144 participants targeted for enrollment in this foundational study.