‘Leqvio reduces LDL-C with twice-yearly dose’

 ▲ Dr. Michael D. Shapiro. Professor of Cardiology at Wake Forest University School of Medicine

First SiRNA drug enters market...may control LDL-C with twice-yearly dosing

아시아 환자에서도 유효성 확인…진료현장서도 일관된 효과

While the “the lower, the better” mantra in LDL-cholesterol (LDL-C) treatment is gaining traction around the world, achieving and maintaining target levels is challenging due to the patients’ poor adherence to existing therapies.

 

In the United States, 50% of patients who are prescribed statins stop taking them within one year, and only 5% remain on treatment after 5 years.

 

Long-term management of LDL-C is crucial, but the burden of traditional oral medications has been leading to poor patient adherence, which is why demand has been rising for new treatment options that can address this unmet need.

 

Dr.

 

Michael D.

 

Shapiro.

 

Profesosr of Cardiology at Wake Forest University School of Medicine

Michael D.

 

Shapiro.

 

Professor of Cardiology at Wake Forest University School of Medicine explained that the siRNA therapy Leqvio could serve as an alternative in this aspect, at a recent meeting with Dailypharm.

 

Leqvio uses siRNAs that are naturally present in the body to reduce LDL-C in the blood by inhibiting the production of the PCSK9 protein, which raises LDL-C.

 

SiRNAs work by binding in a sequence-specific manner to messenger ribonucleic acids (mRNAs) that make disease-causing proteins and then degrade them to block the underlying cause of the disease.

 

Through RNA interference, siRNA causes the degradation of PCSK9 mRNA, which inhibits protein production.

 

When PCSK9 is inhibited, increased low-density lipoprotein receptors (LDLRs) on the cell surface bind LDL-C and reduce LDL-C levels in the blood.

 

Leqvio was approved in the U.S.

 

in December 2021 and has been available since 2022.

 

In Korea, it was approved last year for the treatment of heterozygous familial hypercholesterolemia (HeFH) in patients with atherosclerotic cardiovascular disease (ASCVD) or at risk of ASCVD and has been gradually being used in the field.

 

Leqvio’s greatest strength is its ease of administration.

 

Leqvio can be administered twice a year for effective LDL-C control, compared to daily oral medications or biweekly injections.

 

Professor Shapiro believes that Leqvio will allow more patients to benefit from effective LDL-C reduction.

 

High LDL-C levels are associated with increased cardiovascular risk...“Expectations rise on the use of Leqvio” Cardiovascular disease is the number one cause of death worldwide, and LDL-C management has become an important goal in ASCVD as lowering LDL-C is associated with a lower risk of cardiovascular disease.

 

However, only 24.4% of Korean patients with ASCVD achieved their LDL-C goal, and about 78% of Korean patients with acute myocardial infarction did not achieve their LDL-C goal within 1 year after myocardial infarction.

 

Adherence is also one of the challenges of LDL-C treatment.

 

Patients need to take medication for the rest of their lives to treat LDL-C, but adherence is difficult to maintain.

 

U.S.

 

data shows that 50% of patients stop taking statins within 1 year of being prescribed them, and only 5% remain on treatment at 5 years.

 

“There has been rising hope that siRNA therapies may address the unmet need for adherence in patients with dyslipidemia,” said Professor Shapiro.

 

In particular, Leqvio has the potential to change the landscape of LDL-C treatment with its ability to effectively lower LDL-C and maintain lower levels for longer with twice-yearly dosing.” In three Phase III studies in patients diagnosed with primary hypercholesterolemia, mixed dyslipidemia, or at-risk or heterozygous familial hypercholesterolemia, Leqvio demonstrated LDL-C reductions of up to 52% compared to placebo.

 

In particular, the drug demonstrated 60.5% lower LDL-C compared to placebo in the ORION-18 study in Asian patients, 24% of which were Koreans.

 

“Leqvio may be considered for patients who are not achieving adequate LDL-C control with the maximum tolerated dose of statin,” said Professor Shapiro.

 

“The efficacy and safety of Leqvio in clinical studies have been consistent in real-world practice.

 

The LDL-C reduction effect has been high, around 50%.“ Twice-yearly dosing a major strength...”We need to improve patient access” Leqvio’s twice-yearly dosing regimen dramatically increases the interval between doses compared to oral statins, ezetimibe, and other injectables that require daily dosing.

 

The next hurdle is reimbursement.

 

Novartis, Leqvio’s developer, has reportedly begun reimbursement discussions with the government.

 

“It's not just about lowering LDL-C, it's about maintaining lower LDL-C levels for a longer period of time,” said Professor Shapiro.

 

As LDL-C increases, the risk of cardiovascular disease increases, so we need to improve the care setting to allow consideration of aggressive treatment early on.” However, the burden of cardiovascular disease is underestimated in general due to a lack of understanding of its risk.

 

For example, once a patient suffers a heart attack, there is a high likelihood of heart failure, and the prognosis is much worse than cancer, yet there is a lack of awareness of the seriousness of the disease.

 

“It is important to actively manage LDL-C with drugs as soon as possible,” said Professor Shapiro.

 

In Korea, cardiovascular disease is the second leading cause of death, but it can change to take the lead anytime, so we want to create an environment where people can manage their disease more actively,” said Dr.

 

Shapiro.

 

“Patients with familial hypercholesterolemia have very high cholesterol levels from birth, and if not diagnosed and treated early, they can experience cardiovascular disease at a young age.

 

Statin and ezetimibe therapy alone is not enough, so Leqvio’s effect in achieving and maintaining stable LDL-C reductions renders the drug a quite significant treatment option.”