I have spent close to 30 years working in the cardio-metabolic area in the pharmaceutical industry with products such as Pravachol®, Lipitor®, Glucophage®, Plavix® and ApoA-I Milano (ETC-216). My roles have been as varied as lab scientist, salesperson, marketer, educator and now vice president of strategic marketing and product planning for Esperion. Looking back reminds me of how far we have come. Even as late as the early 1990s, we were still educating physicians about high cholesterol as a risk factor, as well as the difference between good and bad cholesterol.
One of the more remarkable scientific advances of this century is the discovery of PCSK9, which the body uses to regulate low-density lipoprotein cholesterol (LDL-C or “bad cholesterol”). In less than a decade, researchers have moved from describing how PCSK9 functions to evaluating the effect on LDL-C lowering in late-stage clinical trials with investigational drugs that block PCSK9 (called PCSK9 inhibitors).
The PCSK9 discovery has been very important in that it has drawn attention to some astounding facts:
- Heart disease is still the #1 killer of men and women in the United States.
- While two-thirds of patients taking available LDL-C lowering therapies are able to achieve their LDL-C goals, one-third — or more than 11 million patients — still have elevated LDL-C and remain at increased risk for heart disease.
The problems of elevated LDL-C cholesterol and the continuing burden of heart disease remain as major health problems in the United States and throughout the world.
Industry observers widely expect the FDA to approve PCSK9 inhibitors as early as 2015. If that happens, it would represent one of the fastest paths from discovery to approved drug in memory — and would be good news for a sub-set of high-risk patients with very high LDL-C who can’t achieve their LDL-C goals with available therapies.
Theoretically, many patients could benefit from the LDL-C lowering effect of a PCSK9 inhibitor. However, these biological agents must be injected as frequently as once each week rather than administered daily as a pill. This could limit their use. Further, not everyone with an elevated LDL-C needs to lower their LDL-C level by 60-70 percent. In fact, the vast majority of patients not yet achieving their LDL-C goal with available therapies need less than a 30 percent additional LDL-C lowering to get to their goal.
Currently, millions of patients in the United States either can’t take statins because of muscle-related side effects or aren’t able to meet their LDL-C lowering goal with statins or other available therapies. This is where Esperion’s novel, oral small molecule, ETC-1002, may meet an unmet medical need. In seven completed clinical studies, involving more than 300 patients who received ETC-1002, consistent and clinically meaningful reductions in LDL-C of 27-43 percent have been observed. In a more recent Phase 2a clinical study of ETC-1002 in patients with elevated LDL-C levels, we asked whether adding ETC-1002 to10 mg of atorvastatin would be well tolerated and safe, and also whether ETC-1002 added onto atorvastatin could further lower LDL-C after eight weeks. Results showed that ETC-1002 was well tolerated with no major side effects, and that ETC-1002 added on to atorvastatin reduced LDL-C by an incremental 22 percent, whereas patients in the atorvastatin plus placebo group experienced no further reduction in their LDL-C. This incremental lowering of LDL-C could be similar to what a physician would see if they increased their patient’s dose of atorvastatin from 10 mg to 80 mg, or a 50-55 percent decrease in LDL-C.
At Esperion, we believe that ETC-1002 could someday be the best option for the millions of people with hypercholesterolemia who cannot tolerate a statin and those who aren’t able to meet their LDL-C lowering goal — with or without statins – particularly because it is given as a pill, a dosage form that physicians and their patients are used to. We are continuing to study ETC-1002 in a robust Phase 2 clinical development program and look forward to potentially making ETC-1002 available on the market. Physicians and their patients require, and deserve, more treatment options to lower their LDL-C levels and get to their goal.