Innovent's Tafolecimab Monotherapy Cuts LDL Cholesterol by Over 60% in Phase 3 CREDIT-5 Trial

Innovent Biologics, the Hong Kong-listed drugmaker (HKEX: 01801), announced that its PCSK9 antibody SINTBILO, known generically as tafolecimab and carrying the development code IBI306, has met the primary endpoint of a Phase 3 trial called CREDIT-5. The study tested the drug on its own, without a statin alongside it, in Chinese patients with non-familial hypercholesterolemia and mixed hyperlipidemia. By week 12, LDL cholesterol had fallen by more than 60% on average.

The trial was multi-center, randomized, double-blind and placebo-controlled. It enrolled 198 participants, of whom 131 received tafolecimab and 67 received placebo. Before randomization, everyone went through a 4-week run-in during which any drug or product with lipid-lowering effects was prohibited. Participants were then assigned in a 2:1:2:1 ratio to one of four arms: tafolecimab 150 mg every two weeks, placebo every two weeks, tafolecimab 450 mg every four weeks, or placebo every four weeks, all by subcutaneous injection.

The baseline picture was fairly mild. Mean LDL-C was 3.7 mmol/L in the tafolecimab group and 3.8 mmol/L in the placebo group. Mixed dyslipidemia was present in 61.1% of the drug group and 53.7% of the placebo group, and 67.9% and 79.1% respectively were at low cardiovascular risk.

The primary endpoint was the percent change in LDL-C from baseline at week 12. On the 150 mg every-two-weeks schedule, LDL-C fell 65.19%, against 6.61% with placebo. On the 450 mg every-four-weeks schedule, the fall was 64.01%, against 4.31% with placebo. Both comparisons had a p-value below 0.0001. Innovent says a significant drop was visible two weeks after the first dose.

The key secondary endpoints were also met: the proportion of patients reaching LDL-C below 2.6 mmol/L, the proportion below 1.8 mmol/L, the proportion with a reduction of at least 50%, and the mean change in LDL-C. Each tafolecimab group beat its matching placebo group, with p-values all below 0.0001. Other markers moved in the same direction, including non-HDL-C, the total cholesterol to HDL-C ratio, vLDL-C, ApoB, the ApoB/ApoA1 ratio and Lp(a), which dropped by nearly 50%. Innovent says this suggests the drug improves lipid-related risk factors for atherosclerotic cardiovascular disease and is expected to lower patients' cardiovascular risk; the trial itself measured lipid levels, not cardiovascular events.

On safety, the company reports no severe or serious treatment-emergent adverse events, no adverse event leading to discontinuation or interruption of the study drug, and no new safety signal compared with earlier studies.

Professor Yida Tang of Peking University Third Hospital, the lead principal investigator, framed the result around the limits of statins. They remain the first-line standard of care, he said, but some patients respond poorly to statin monotherapy or combinations because of intolerance or difficulty keeping up long-term treatment. He argued the trial supports PCSK9 antibodies as a standalone lipid-lowering option, giving patients and clinicians who need non-statin treatment new clinical evidence.

SINTBILO is the first domestically developed PCSK9 antibody commercialized in China, and it has been on the National Reimbursement Drug List since January 1, 2025. Innovent says it has reached more than 1 million patients since launch. The company plans to file a new indication application with China's National Medical Products Administration in the near future, aiming to position the drug as a more convenient first-line option for people with hyperlipidemia. The regulatory decision is the next thing to watch.