Repatha: Injectable Cholesterol Drug Study Results Positive

Repatha, Amgen’s injectable cholesterol lowering drug, in combination with statin therapy, lowered “bad” LDL more than either drug alone, a new study has revealed.

Nearly 2/3 of study participants experienced plaque regression with Repatha plus statins.

Presented at the American Heart Association’s annual meeting, the results showed, in addition, that the drug combination caused declines in plaques which had been building up in the heart vessel walls for a majority of high-risk heart patients after 18 months of treatment.

The GLAGOV Phase 3 coronary intravascular ultrasound imaging trial involved 968 patients and compared monthly injections with Repatha plus a statin with statins alone. Repatha (evolocumab) is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of certain patients with elevated low-density lipoprotein cholesterol (LDL-C).

Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said:

“The cardiovascular community began conducting imaging studies with LDL-C therapies to measure slowing of atherosclerotic disease progression. This study shows that maximal LDL-C reduction with Repatha can actually regress coronary atherosclerotic disease compared to statins alone. In fact, nearly two-thirds of patients on Repatha in this trial, the vast majority of whom were already on high to moderate intensity statin therapy at baseline, experienced a reduction in plaque burden.”

No new safety concerns were identified in the GLAGOV trial.

The incidence of treatment-emergent adverse events was comparable among both groups (67.9 percent Evolocumab; 79.8 percent placebo). Adverse events of clinical importance reviewed in this study included myalgia (7.0 percent Repatha; 5.8 percent placebo), new diagnosis of diabetes mellitus (3.6 percent Evolocumab; 3.7 percent placebo), neurocognitive events (1.4 percent Evolocumab; 1.2 percent placebo) and injection site reactions (0.4 percent Evolocumab; 0.0 percent placebo).

Repatha, which costs more than $14,000 a year before discounts and rebates, has been prescribed more than 100,000 times in the United States since its approval. However, two-thirds of patients are ultimately denied, according to Amgen.

Harper added,

“The compelling data from GLAGOV remove any scientific doubt about the ability of Repatha to lower LDL-C and the impact it has on the critical underlying disease process. We remain concerned that many patients are experiencing barriers to accessing Repatha, despite their physician’s treatment recommendations. We look forward to our outcomes study, FOURIER, and will continue to work with payers to improve access for patients who need additional LDL-C lowering.”

Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

Puri, Rishi et al.
Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV)
American Heart Journal , Volume 176 , 83 – 92; DOI: http://dx.doi.org/10.1016/j.ahj.2016.01.019