Primary Endpoint in Phase II Trial: Pacibekitug met in 2025

Primary endpoint in Phase II trial is met by Pacibekitug in 2025, showing major CRP and Lp(a) reductions for patients with chronic kidney diseases. 

Tourmaline Bio’s investigational antibody pacibekitug has achieved its primary endpoint in the Phase II Tranquility trial. This is welcome news for millions of people living with chronic kidney disease (CKD), who are at risk of cardiac disease worldwide. This success drew the attention of Novartis, which is investing USD 1.4B in Tourmaline Bio and its earlier Pfizer drug, signaling a strong outcome in the future of the medication. 

Chronic kidney disease affects an estimated 10-14% of the general population, which is around 850 million people globally. Among them, cardiovascular disease is the leading cause of death, particularly in patients under dialysis, with 20 to 30 times higher cardiac risks. 

The risk of heart attack and stroke is mainly due to the residual inflammation, often measured by the increase in C-reactive protein (CRP), formed because of overreactive Interleukin-6 (IL-6). While therapies exist to control cholesterol and blood pressure, many continue to face elevated risks of heart disease. Pacibekitug directly targets IL-6 in phase II drug trials and offers the possibility of reducing inflammatory cardiovascular risk in ways existing treatments cannot. 

CRP in Chronic Kidney Disease: The Hidden Risk Factor 

The deadly burden in CKD is persistent inflammation leading to an increase in CRP. The high (hs-CRP) is a well-recognized biomarker of systemic inflammation, and levels are often chronically elevated in kidney disease. The impaired kidneys cannot clear the inflammatory molecules adequately, needing an external molecule to stop their progression.  

Lowering the CRP levels can be achieved by pacibekitug, which met its primary endpoints in the Phase II trial, giving promising results. When the CPR levels are reduced, the risk of atherosclerosis, vascular stiffening, and destabilization of plaques, leading to heart attacks and stroke, is also reduced. 

 

Why IL-6 Matters: The Inflammatory Switch 

The main reason behind elevated CPR is the interleukin-6, which signals the liver to produce CRP, accelerating systemic inflammation. Overactive IL-6 signaling keeps CRP levels dangerously high, maintaining cardiovascular risk. So, the primary end point in phase II trial was time-dependent reduction in hs-CRP through 90 days, aiming to reduce the risk for heart diseases. 

Failure to reduce IL-6–driven CRP means CKD patients remain at risk for heart failure, arrhythmias, and sudden cardiac death. This is why IL-6 inhibition has become one of the most promising strategies to tackle residual risk in cardiovascular disease. 

How Pacibekitug Works: Mode of Action 

Pacibekitug is a monoclonal antibody that binds to IL-6, preventing it from activating CRP production in the liver. This shuts down the cascade, lowering the systemic inflammation, measured by reduction in hs-CPR.  

The advantage of this drug is its quarterly dose option, which improves long-term adherence for patients managing multiple drugs for their diverse chronic conditions. 

The Tranquility Primary Endpoint in Phase II Trial 

The Tranquility study is a randomized, double-blind, placebo-controlled Phase II drug trial investigating pacibekitug in patients with stage 3–4 CKD with elevated hs-CRP. 

• Primary endpoint in phase 2 clinical trial: time-bound percent reduction in hs-CRP through Day 90. 

• Study arms: 15 mg monthly, 25 mg quarterly, 50 mg quarterly dosing, versus placebo. 

• Control group: placebo recipients ensured reductions were attributable to pacibekitug. 

Results Primary Endpoint in Phase II Trial: 

• The 50 mg quarterly arm reduced hs-CRP by ~85–86% by Day 90. 

• The 15 mg monthly and 25 mg quarterly arms achieved ~75–85% reductions, all highly significant versus placebo (p<0.0001). 

• Reductions were rapid, deep, and durable, sustained through dosing intervals. 

• Safety profile was favorable, with adverse events similar to placebo. 

Clinical Research Phases Summary
Trial Name	TRANQUILITY Phase II
Population	CKD patients with elevated CRP
Dosing Arms	15 mg monthly / 25 mg quarterly / 50 mg quarterly
Primar Endpoint	% reduction in hs-CRP at Day 90
Key Results	75–86% CRP reduction, p<0.0001
Added benefits	Lp(a) reduction
Next Step	Phase III outcome trials

Meeting the primary endpoint in the phase 2 trial confirms that pacibekitug effectively blocks IL-6, delivering a powerful anti-inflammatory effect. 

Added Advantage: Reduction in Lipoprotein(a) 

Premature Atherosclerotic cardiovascular disease (ASCVD) is found to be associated with elevated Lp(a), a genetically determined risk factor that is largely resistant to current therapies (NCBI). Pacibekitug also showed exploratory reductions in lipoprotein(a), or Lp(a), addressing two distinct residual risk pathways. For CKD patients, who already face layered risks, this dual effect could be transformative. 

Why This Matters for Patients and Industry 

For patients: 

• Patients with CKD having high levels of CRP finally have a targeted therapy designed to address their unmet residual inflammatory risk. 

• The dual benefit of CRP and Lp(a) could significantly lower heart attack and stroke risk, where standard therapies fall short. 

For the pharmaceutical industry: 

• Novartis’ $1.3 billion acquisition of Tourmaline Bio highlights its strategic commitment to inflammatory and cardiovascular therapeutics. 

• Pacibekitug complements Novartis’ existing cardiovascular pipeline, positioning the company at the forefront of inflammation-modifying therapies. 

 

Phase III Clinical Research  

While biomarker wins are essential, regulators and clinicians will want to see event-driven outcomes: reductions in heart attacks, strokes, and cardiovascular deaths. These will require large Phase III studies with better outcomes compared with primary end points in phase II trials, which is already on the horizon as Novartis integrates pacibekitug into its pipeline. 

If successful, pacibekitug could become the first IL-6 inhibitor widely used for cardiovascular prevention, especially in CKD, where residual risk remains dangerously high. 

Conclusion: A Turning Point in Managing Residual Risk 

Pacibekitug’s success in meeting its Phase II primary endpoint is more than a scientific milestone; it is a hopeful signal for the 850 million people worldwide with CKD. By cutting down the elevated CRP levels and showing potential to reduce Lp(a), the drug addresses two of the major challenges in cardiovascular medicine. 

With Novartis’ global reach and resources, the future looks bright for pacibekitug. If Phase III confirms its promise, CKD patients may finally see a therapy that closes the gap in residual risk, paving the way for a new era of cardiovascular prevention. 

Final Thoughts 

Behind every such milestone lies the science of trial design, endpoint selection, biomarker validation, and regulatory strategy, the very foundations of clinical research. At CliniLaunch, our PG Diploma in Clinical Research Course equips learners with these same skills, preparing the next generation of professionals to contribute to trials like TRANQUILITY and beyond. 

The need for trained clinical researchers is rapidly increasing as the pharmaceutical world advances with innovative drugs, saving the lives of millions. If you’re inspired by how Pacibekitug’s journey from the lab to Phase II results is shaping the future of medicine, then it is time for you to build your expertise.