PCSK9 Inhibitors as Cholesterol
Drugs
What is PCSK9?
Proprotein convertase
subtilisin/kexin type 9, also known as PCSK9, is an enzyme that in humans is
encoded by the PCSK9 gene. PCSK9 has medical significance because it acts in
cholesterol homeostasis. Drugs that block PCSK9 can lower low-density
lipoprotein cholesterol (LDL-C), and are beginning Phase III clinical trials to
assess their safety and efficacy in humans, and to determine if they can
improve outcomes in heart disease.
PCSK9 Inhibitors
Two PCSK9 inhibitors, alirocumab
and evolocumab, are in late-stage clinical development, because of their
ability to lower LDL-C in patients for whom other treatments have been
ineffective. Both of them are as the name suggest, -umab or monoclonal
antibodies.
Costly than Statins
PCSK9 inhibitors will undoubtedly
be a more costly treatment option than the current standard LMT, statins, which
are a largely generalized class.
Trials and Results
The clinical trials for each of
the PCSK9 inhibitors in development were designed to evaluate the long-term
safety and tolerability of evolocumab (OSLER) and alirocumab (ODYSSEY) in high
CVD-risk patients with hypercholesterolemia not effectively controlled with
their current lipid-modifying therapy (LMT). The clinical trials for both
alirocumab and evolucumab were global and included a broad cross-section of
subjects-all of whom had difficult-to-treat hypercholesterolemia. The studies
cut across all demographic categories, including age, race, nationality and
economic status. Each drug lowered LDL-C by about 60% and decreased the rate of
CVD events, including heart attack, heart failure leading to hospitalization
and death, by about 50%.
Advantages
The advantage of PCSK9 inhibitors
is that dosing will only involve a subcutaneous injection either once or twice
per month. Patients will receive pre-filled syringes that they can easily
administer at home.
Side-Effects
Overall, patients treated with
PCSK9 inhibitors had higher rates of nonspecific side effects, such as
arthralgia, headache, limb pain and fatigue, compared with placebo-treated
patients. There were also more injection-site reactions in subjects treated
with PCS9 inhibitors. Moreover, 1% to 1.5 % of patients experienced
treatment-related neurocognitive effects, mainly confusion and some memory
loss.
Evolocumab (Repatha) is developed by Amgen and Alirocumab (Praluent) is Sanofi and Regeneron product.
Evolocumab (Repatha) is developed by Amgen and Alirocumab (Praluent) is Sanofi and Regeneron product.