Saturday, March 21, 2015

PCSK9 Inhibitors as Cholesterol Drugs

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%.


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.


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.