What Is Pelacarsen?
Pelacarsen is an investigational drug currently being studied for its potential to reduce elevated levels of lipoprotein(a), often referred to as Lp(a). High Lp(a) levels are a known risk factor for cardiovascular disease. The provided trial descriptions do not detail the specific mechanism by which Pelacarsen works, but it is being investigated as a subcutaneous injection given monthly.
While specific FDA approvals are not detailed for Pelacarsen in the provided trial information, current therapeutic options for cardiovascular risk reduction in patients with severely elevated Lp(a) levels, such as lipoprotein apheresis, are described as expensive, burdensome, and time-consuming. Pelacarsen is being studied as a potential alternative to address these challenges. There are currently 10 clinical trials investigating Pelacarsen, with a total enrollment of 7,279 participants. The first trial began on 2021-08-06, and the latest is projected to conclude on 2026-04-08.
Uses and Conditions Under Study
Pelacarsen is primarily being investigated for conditions related to elevated lipoprotein(a) (Lp(a)) and its impact on cardiovascular health. High Lp(a) levels are a genetic risk factor that can contribute to the development and progression of various heart conditions. Reducing Lp(a) is a key focus of Pelacarsen's development.
Conditions under study include:
- Atherosclerotic Cardiovascular Disease (ASCVD) and related conditions: Pelacarsen is being studied in patients with Atherosclerotic Cardiovascular Disease, including specific trials for Acute Coronary Syndrome and Aortic Stenosis. These conditions are characterized by the buildup of plaque in the arteries, which can lead to heart attacks, strokes, and other serious cardiovascular events. Pelacarsen aims to reduce Lp(a) levels, which may in turn reduce the risk or progression of these diseases. There are 5 trials specifically mentioning ASCVD or related acute coronary events.
- Hyperlipoproteinemia (a) and Cardiovascular Disease: Several trials are directly investigating Pelacarsen in patients with Hyperlipoproteinemia (a), which means abnormally high levels of Lp(a), and its link to overall Cardiovascular Disease. These studies aim to confirm the drug's ability to lower Lp(a) and assess the clinical benefits of this reduction. There are 2 trials focusing on these specific conditions.
- Other studies: Pelacarsen is also being studied in healthy participants and those with hepatic impairment to understand its pharmacokinetics (how the body processes the drug) and safety profile across different populations. One trial also examines genetic polymorphisms, likely to understand how genetic variations might influence Lp(a) levels or the drug's effectiveness.
Dosing
Pelacarsen is administered as a solution for injection, typically provided in a prefilled syringe for subcutaneous (s.c.) injection. The most commonly studied dose in multiple-dose trials is 80 mg, administered monthly or every four weeks (Q4W).
In early-stage studies, various strengths have been investigated to determine the optimal dosage. These include single ascending dose (SAD) studies where participants received Pelacarsen at 20 mg, 40 mg, or 80 mg. For ongoing or planned multiple-dose (MD) studies, the standard investigational dose is 80 mg.
Studies have also been conducted in specific populations, such as healthy participants and individuals with mild hepatic impairment, to assess how the drug is processed by the body and to ensure its safety and efficacy across different patient profiles. All mentioned dosages are for adult participants, as no investigational pediatric doses are detailed in the provided data.
Side Effects
The most commonly reported side effect in patients taking Pelacarsen was injection site reactions, which occurred in 17.5% of patients, compared to 1.3% of patients receiving a placebo. Other common side effects reported in clinical trials for patients with elevated lipoprotein(a) (NCT03399265) included:
- Arthralgia (joint pain): 12.1% of patients taking Pelacarsen experienced this, compared to 8.1% on placebo.
- Headache: 11.5% of patients taking Pelacarsen experienced this, compared to 9.4% on placebo.
- Nausea: 10.5% of patients taking Pelacarsen experienced this, compared to 8.4% on placebo.
- Diarrhea: 10.2% of patients taking Pelacarsen experienced this, compared to 7.7% on placebo.
- Fatigue: 9.5% of patients taking Pelacarsen experienced this, compared to 7.4% on placebo.
- Vomiting: 8.8% of patients taking Pelacarsen experienced this, compared to 6.4% on placebo.
In a separate open-label study involving patients with end-stage renal disease (ESRD) on hemodialysis (NCT03982907), specific side effects related to this population were observed. These events did not have a placebo comparison in this particular trial:
- AV fistula complication: 3.3% of patients.
- Hyperkalemia (high potassium levels): 2.2% of patients.
Clinical Trial Results
Results for Elevated Lipoprotein(a)
A Phase 2 study (NCT03399265) investigated Pelacarsen in patients with elevated lipoprotein(a) (Lp(a)) levels. The primary goal was to measure the change in Lp(a) levels from the start of the study to Week 36. Patients treated with Pelacarsen experienced a significant median reduction in Lp(a) levels of 80%, while patients on placebo saw a median increase of 1%.
Key secondary outcomes also showed positive results:
- 98% of patients receiving Pelacarsen achieved an Lp(a) level below 50 mg/dL, a common target for cardiovascular risk reduction, compared to 1% of patients on placebo.
- 92% of patients on Pelacarsen reached an Lp(a) level below 30 mg/dL, while no patients on placebo achieved this.
- Pelacarsen also reduced LDL-C (bad cholesterol) by 15%, compared to a 1% reduction with placebo.
These findings indicate that Pelacarsen effectively lowers Lp(a) levels and helps a large majority of patients reach target Lp(a) goals, along with reducing other lipid markers.
Results for Hyperphosphatemia in Dialysis Patients
An open-label Phase 2 study (NCT03982907) evaluated Pelacarsen in patients with end-stage renal disease (ESRD) on hemodialysis who had hyperphosphatemia (high phosphate levels). The study assessed the change in serum phosphate levels from baseline to Week 12 across different doses of Pelacarsen. Lowering phosphate levels is beneficial for these patients.
- Patients receiving 80 mg of Pelacarsen experienced an average reduction in serum phosphate of 0.8 mg/dL.
- Patients on 120 mg of Pelacarsen saw an average reduction of 1.1 mg/dL.
- The 160 mg dose led to an average reduction of 1.3 mg/dL.
The study also looked at the percentage of patients who achieved a serum phosphate level below 4.5 mg/dL, which is a common therapeutic target:
- 33% of patients on 80 mg of Pelacarsen reached this target.
- 44% of patients on 120 mg of Pelacarsen reached this target.
- 56% of patients on 160 mg of Pelacarsen reached this target.
These results suggest that Pelacarsen can effectively reduce serum phosphate levels and help a significant portion of dialysis patients achieve their phosphate targets, with higher doses showing greater reductions.
Currently Recruiting Trials
Pelacarsen is currently being investigated in several clinical trials across various stages of development, offering opportunities for patients to contribute to medical research. These studies aim to further understand the drug's safety and effectiveness for different cardiovascular conditions. One such study, NCT07517263, is a Phase 3 open-label extension study sponsored by Novartis Pharmaceuticals. It aims to evaluate the long-term safety and tolerability of Pelacarsen (TQJ230) in participants who have already completed a previous double-blind study (CTQJ230A12301). This trial is designed for individuals with Cardiovascular Disease and Lipoprotein(a) and plans to enroll up to 5700 participants. Another Phase 3 rollover extension program, NCT06875973, also sponsored by Novartis Pharmaceuticals, provides post-trial access to Pelacarsen (TQJ230) for participants who successfully completed either of two parent double-blind studies (CTQJ230A12303 or CTQJ230A12304). This study focuses on Atherosclerotic Cardiovascular Disease and targets an enrollment of 599 individuals. For those with established Atherosclerotic Cardiovascular Disease (ASCVD) and elevated lipoprotein(a) (Lp(a)) who are already receiving inclisiran for high low-density lipoprotein cholesterol, the Phase 3 study NCT06813911 is evaluating Pelacarsen (TQJ230) against a placebo. Sponsored by Novartis Pharmaceuticals, this trial seeks to enroll 340 participants. A Phase 2 multicenter trial, NCT05646381, is investigating the impact of Pelacarsen (TQJ230) on the progression of calcific aortic valve stenosis. This study, sponsored by Novartis Pharmaceuticals, compares monthly subcutaneous doses of 80mg Pelacarsen (TQJ230) to a placebo, with an enrollment target of 502 participants.Where to Participate
Clinical trials for Pelacarsen are being conducted across a wide geographic area, with 136 sites located in 103 cities across 27 states. This broad reach aims to make participation accessible to a diverse patient population. Top locations for participation include:- Miami, Florida (9 sites)
- Houston, Texas (6 sites)
- Detroit, Michigan (5 sites)
- Miami Lakes, Florida (5 sites)
- Boston, Massachusetts (5 sites)
- Beverly Hills, California (4 sites)
- Falls Church, Virginia (4 sites)
- Flint, Michigan (4 sites)
- Alexandria, Virginia (4 sites)
- Winston-Salem, North Carolina (3 sites)