Page 34 - GALENIKA MEDICAL JOURNAL

MK-0616 lowered during more than two years of follow-up, suppor-
ting the potential for a lasting treatment effect. Recently,
MK-0616 is an oral macrocyclic PCSK9 inhibitor currently at the American Heart Association conference (November
in clinical trial phase. The second phase of clinical trials has 2023), the first results of this therapy in humans (phase Ib
shown that orally administered PCSK9 inhibitors at daily do- clinical trial) were presented, showing good and promising
ses ranging from 6 to 30 mg resulted in a reduction of LDL outcomes .
52
cholesterol by up to 60.9% compared to placebo after an
8-week follow-up period in patients with hypercholestero-
lemia and atherosclerotic cardiovascular disease previously
treated with statins .
49
PCSK9 vaccines represent a new therapeutic strategy
that would enable the intrinsic production of antibodies
against PCSK9 . A liposomal immunogenetic compound
50
consisting of PCSK9-tetanus peptide with an aluminum
adjuvant is a new formulation of PCSK9 vaccine that has de-
monstrated long-lasting synthesis of PCSK9 antibodies and
reduction in LDL and VLDL cholesterol levels in laboratory
mice by 51.7% in BALB/c and 19.2% in C57BL/6 animal mo-
dels .
50

Gene therapy for high cholesterol

Encouraging research in animal models has demon-
strated the potential for gene therapy for high cholesterol.
Specifically, mRNA encoding the PCSK9 gene (known as
VERVE-101) has been synthesized and packaged into lipid
nanoparticles. Preclinical studies in mice and non-human
primates (NHP) have shown that a single intravenous ad-
ministration of VERVE-101 can inactivate the PCSK9 gene in
the liver . NHP treated with VERVE-101 experienced a signi-
51
ficant reduction in LDL levels, which remained permanently

Conclusion

Considering that dyslipidemia is a significant risk factor for cardiovascular diseases, lipid-lowering
drugs are important not only in primary but also in secondary prevention of these diseases.
Although according to all current guidelines, LDL levels remain the primary therapeutic target,

increasing attention is being paid to residual cardiovascular risk. Statins are the most commonly
prescribed drugs worldwide, although, despite their use, a large number of patients do not achieve
the recommended LDL target levels. Therefore, statins can be combined with ezetimibe and PCSK9
inhibitors. Bempedoic acid is an approved therapeutic alternative for patients who do not tolerate
statins. Inclisiran is a PCSK9 inhibitor counterpart, however, the use of inclisiran could improve
patient compliance due to its dosing regimen. Pelacarsen and olpasiran are future therapeutic
strategies aimed at lowering Lp(a), which is an independent risk factor for cardiovascular diseases.
Evinacumab, lomitapide, mipomersen, volanesorsen, and olezarsen are drugs that primarily affect
various steps in the metabolism of atherogenic lipoproteins, thus representing a significant new

approach in cardiovascular disease prevention. In the future, the results of ongoing randomized
controlled trials are expected to definitively demonstrate the effectiveness of these new therapeutic
options for lowering lipid levels in the prevention of cardiovascular diseases.

32 DOI: 10.5937/Galmed2409031L