What Is Olpasiran?
Olpasiran is a medication currently being investigated in clinical trials. It is administered as a subcutaneous (SC) injection, meaning it is given under the skin. While specific FDA approvals are not detailed in the provided data, Olpasiran is being studied for its potential role in managing various cardiovascular conditions. The drug is primarily being investigated for conditions such as Cardiovascular Disease, Atherosclerotic Cardiovascular Disease, and Elevated Serum Lipoprotein(a). These studies aim to understand how Olpasiran might help improve outcomes for patients with these conditions.
Clinical trials involving Olpasiran began in 2020, with the latest trial expected to conclude in 2025. A total of 9 trials have been conducted or are ongoing, with 2 currently recruiting participants and 5 already completed. These trials have involved a significant number of participants, with a total enrollment of 19,098 individuals across all studies. Amgen is the sole sponsor for all clinical investigations into Olpasiran.
Uses and Conditions Under Study
Olpasiran is being studied for its potential to treat several conditions, primarily focusing on cardiovascular health and specific organ impairments.
- Cardiovascular Conditions: Olpasiran is being investigated for its role in managing Cardiovascular Disease, Atherosclerotic Cardiovascular Disease, and Elevated Serum Lipoprotein(a). Cardiovascular disease encompasses a range of conditions affecting the heart and blood vessels. Atherosclerotic cardiovascular disease specifically refers to the buildup of plaque in the arteries, which can lead to serious health issues. Elevated serum lipoprotein(a) is a genetic risk factor for cardiovascular disease. The drug is being studied in 3 trials for Cardiovascular Disease, 1 trial for Atherosclerotic Cardiovascular Disease, and 1 trial for Elevated Serum Lipoprotein(a), suggesting a focus on addressing these significant risk factors and conditions.
- Impaired Organ Function: Studies are also exploring Olpasiran in individuals with Hepatic Impairment and Renal Impairment. These trials, including 1 trial for Hepatic Impairment and 1 trial for Renal Impairment, are crucial for understanding how the drug is processed and its safety profile in patients whose liver or kidney function may be compromised. This helps ensure appropriate dosing and monitoring if the drug were to be used in these populations.
- Basic Science: One trial for Basic Science is also listed. These types of studies often aim to understand the fundamental biological effects of a drug, how it works at a cellular or molecular level, or to explore new biomarkers. This foundational research is essential for guiding further clinical development.
Dosing
Olpasiran is administered as a subcutaneous (SC) injection, meaning it is given under the skin. Clinical trials have investigated various dosing regimens and forms of Olpasiran.
While specific strengths (e.g., in milligrams) are not detailed in the provided data, studies have explored different doses, referred to as "Olpasiran Dose A," "Olpasiran Dose B," and various doses across different treatment arms (e.g., "Arm 1 Olpasiran Dose 1" through "Arm 4 Olpasiran Dose 4"). This indicates that researchers are evaluating a range of quantities to determine the most effective and safest dose for different conditions.
One specific regimen mentioned in the trial descriptions is a subcutaneous injection given once every 12 weeks (Q12W). This extended dosing interval could be beneficial for patient convenience.
In addition to standard dosing, special studies have been conducted to understand Olpasiran's behavior in specific populations. These include "Single Dose Olpasiran Renal Impairment" and "Single Dose Olpasiran Hepatic Impairment" studies, alongside their respective normal function counterparts. These investigations are crucial for determining if dose adjustments are necessary for patients with impaired kidney or liver function, ensuring the drug can be used safely and effectively in a broader patient population. The data does not specify any investigational pediatric doses.
Side Effects
In a clinical trial involving 450 patients who received Olpasiran, the most common side effect was headache. 6.4% of patients taking Olpasiran experienced headache, compared to 3.7% on placebo.
Other common side effects reported more frequently with Olpasiran than with placebo included:
- Back pain: 5.6% of patients on Olpasiran compared to 2.8% on placebo.
- Fatigue: 4.9% of patients on Olpasiran compared to 3.7% on placebo.
- Urinary tract infection: 3.3% of patients on Olpasiran compared to 0.9% on placebo.
- Nasopharyngitis (common cold): 3.3% of patients on Olpasiran compared to 0.9% on placebo.
- Upper respiratory tract infection: 3.3% of patients on Olpasiran compared to 2.8% on placebo.
- Arthralgia (joint pain): 2.9% of patients on Olpasiran compared to 1.9% on placebo.
- Non-cardiac chest pain: 2.7% of patients on Olpasiran compared to 0.9% on placebo.
Some side effects occurred at similar or lower rates in patients taking Olpasiran compared to placebo, such as immunisation reaction (4.4% vs 4.7%), myalgia (muscle pain, 3.1% vs 3.7%), and hypertension (2.7% vs 2.8%).
Clinical Trial Results
Clinical studies have investigated the effects of Olpasiran on lipoprotein(a) (Lp[a]) and other lipid levels.
Lipoprotein(a) Reduction Study (NCT04270760)
This dose-finding study evaluated different doses and dosing frequencies of Olpasiran compared to placebo. The primary goal was to assess changes in Lp(a) levels, a key risk factor for cardiovascular disease.
- At Week 36, Olpasiran significantly reduced Lp(a) levels from baseline, while placebo showed an increase. Patients receiving 10 mg every 12 weeks experienced a 66.9% reduction in Lp(a). Higher doses led to even greater reductions: 75 mg every 12 weeks resulted in a 93.8% reduction, and a 97.5% reduction was achieved with 225 mg every 12 weeks. A dose of 225 mg every 24 weeks also reduced Lp(a) by 96.9%. In contrast, patients on placebo experienced a 3.6% increase in Lp(a).
- These reductions were largely maintained at Week 48. The 225 mg every 12 weeks dose continued to show the highest reduction at 97.3%. Placebo patients again saw an increase of 3.6% in Lp(a).
The study also observed reductions in other lipid markers:
- Low-density lipoprotein cholesterol (LDL-C) levels were reduced across all Olpasiran doses at Week 36, ranging from 11.5% to 18.5%, while placebo patients experienced a 6.2% increase. Similar reductions were seen at Week 48, compared to a 10.1% increase in the placebo group.
- Apolipoprotein B (ApoB) levels also decreased with Olpasiran treatment. At Week 36, reductions ranged from 7.2% to 11.5% across the active treatment groups, whereas ApoB increased by 12.3% in the placebo group.
Pharmacokinetics and Pharmacodynamics in Chinese Participants (NCT04987320)
This study assessed Olpasiran in Chinese participants with elevated Lp(a). It found that Olpasiran significantly reduced Lp(a) levels:
- For the high dose of Olpasiran, mean Lp(a) reductions ranged from 81.5% to 99.2%.
- For the low dose of Olpasiran, mean Lp(a) reductions ranged from 32.9% to 94.8%.
Regarding safety, 10 participants in the high-dose group and 12 participants in the low-dose group experienced treatment-emergent adverse events. The apparent terminal elimination half-life of Olpasiran was approximately 6 to 6.7 hours.
Currently Recruiting Trials
Olpasiran is currently being investigated in several clinical trials, primarily focusing on its potential to improve cardiovascular health. These studies aim to understand how Olpasiran might help patients with existing cardiovascular disease or those at risk of developing it.
One significant study is the "Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction - Coronary Computed Tomography Angiography Trial," identified as NCT07293260. This Phase 3 trial, sponsored by Amgen, is designed to evaluate how Olpasiran, compared to a placebo, affects the volume of non-calcified plaque (NCP) in the arteries, as measured by Coronary Computed Tomography Angiography (CCTA). It is currently seeking to enroll 406 participants who have cardiovascular disease.
Another large-scale investigation is the "OCEAN(a)-PreEvent - Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction to Prevent First Major Cardiovascular Events," known by its ID NCT07136012. This Phase 3 trial, also sponsored by Amgen, aims to assess Olpasiran's effect on reducing the risk of major cardiovascular events. These events include coronary heart disease death, myocardial infarction, or urgent coronary revascularization in individuals at risk for a first major cardiovascular event who also have elevated lipoprotein(a) (Lp[a]). This study plans to enroll a substantial 11,000 participants with cardiovascular disease.
Where to Participate
For those interested in participating in Olpasiran clinical trials, study sites are widely distributed across the United States. There are currently 199 sites located in 166 cities across 37 states. This broad reach aims to make participation accessible to a diverse patient population.
Top locations with multiple recruiting sites include:
- Dallas, Texas (4 sites)
- Greensboro, North Carolina (3 sites)
- Houston, Texas (3 sites)
- New York, New York (3 sites)
- Phoenix, Arizona (3 sites)
- McKinney, Texas (3 sites)
- Humble, Texas (2 sites)
- Austin, Texas (2 sites)
- Cincinnati, Ohio (2 sites)
- Bowie, Maryland (2 sites)
Eligibility criteria for these trials generally require participants to be between 35 and 105 years of age, and all genders are welcome. These studies are not seeking healthy volunteers or children; participants must have specific medical conditions relevant to the research.
Development Timeline
The journey of Olpasiran began with its first clinical trial on February 17, 2020. Since then, its development has been consistently driven by Amgen, which has sponsored all 9 trials conducted to date. The research program has enrolled a total of 19,098 participants across various studies.
Initially, Olpasiran's development explored conditions such as IBS-C and hyperphosphatemia. Over time, the focus expanded, incorporating studies in Basic Science, Hepatic Impairment, and Renal Impairment. A significant shift in the pipeline has led to a strong emphasis on cardiovascular health, particularly in relation to Elevated Serum Lipoprotein(a), which is now the primary focus of its most advanced trials.
The drug's progression through clinical phases reflects this evolving understanding, starting with 4 Phase 1 trials, moving through 1 Phase 2 trial, and now featuring 3 Phase 3 trials. This progression indicates a growing confidence in Olpasiran's potential. The latest trial is projected to conclude by December 19, 2025, marking a significant milestone in its ongoing development.