Results released by Sanofi and Regeneron of their PCSK9 inhibitor were based on prior clinical trials.
An analysis of 6 clinical trials released yesterday showed that most patients who added alirocumab to their treatment regimen for high cholesterol were achieve their target within 8 weeks. Of those who had to move up to a higher dose, most were able to get to goal, according to results presented Tuesday at the American Heart Association Scientific Sessions in Orlando, Florida.
The results were announced by Sanofi and Regeneron, who market alirocumab under the name Praluent. The injectable drug was the first of a class called PCSK9 inhibitors approved by FDA on July 24, 2015. A second version, evolocumab, marketed by Amgen as Repatha, was approved August 27, 2015. Alirocumab is given every 2 weeks; evolocumab is as well but is reportedly working on a once-a-month version.
PCSK9 inhibitors have been among the most anticipated and controversial drugs to hit the market in years. While their cholesterol-fighting powers have not been questioned, there has been debate about just who should get them, given their cost. The FDA labels are not as broad as the approvals in Europe, pending long-term cardiovascular (CV) safety trials.
Both drugs listed above $14,000 a year wholesale when first approved, but it is believed that EspressScripts negotiated a substantial discount when it agreed to list both on its national formulary recently (but the precise amount was not announced).
The 2 drugs are monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that when blocked results in dramatically lower levels of low-density lipoprotein (LDL) cholesterol. PCSK9 stymies the liver from effectively eliminating LDL cholesterol on its own. When it was found that persons who lacked this enzyme had abnormally low cholesterol levels, researchers immediately recognized the therapeutic potential and began looking for ways to block PCSK9.
The analysis released late Tuesday culled data from 6 Phase 3 ODYSSEY trials in which patients took 75 mg doses of alirocumab in addition to statins, and had their dose increased to 150 mg at week 12 if they had not achieved their LDL cholesterol targets by week 8.
Data separated out patients with diabetes from those who did not, and noted that those with diabetes had lower baseline LDL cholesterol levels.
Results. Three analyses were completed based on a pool of patients that included 1048 with diabetes and 2444 without at the start of the trials. The first analysis looked at 1291 patients with high cardiovascular risk or an inherited condition, familial hypercholesterolemia (FH). This examination found that 74% of the patients who took the 75 mg dose of the study drug achieved their LDL target by week 8. The remaining 26% switched to the 150 mg dose at week 12, with the following results: at week 24, 61% of this group had reached goal with an additional LDL reduction of 14%.
Adverse events were similar at the high dose and the low dose, but they were higher (66% in both arms with the study drug) than in arms of patients who took ezetimibe (55% and 56%).
Patients with diabetes. A separate analysis that looked at a larger group of patients found that those with diabetes who took the study drug had lower LDL cholesterol, with differences depending on the dose. The mean difference at week 24 was a reduction of 44% for those on the 75 mg dose and 58% for those on the 150 mg dose, compared with placebo.
For this group the most common adverse events were nasopharyngitis (11% alirocumab, 10% placebo) and upper respiratory tract infections (8% alirocumab, 9% placebo). A third analysis with a larger group of patients found no increased risk of side effects related to diabetes among those who didn’t already have the disease when they started the trials. Also, there was no evidence that the drug affected the likelihood of new onset diabetes or prediabetes. A long-term outcomes trial will provide more data on these issues, as well as CV effects.
Ginsberg HN, Farnier M, Robinson JG, et al. Efficacy and safety of alirocumab: pooled analyses of 1048 individuals with diabetes mellitus from five placebo-controlled phase 3 studies of at least 52 weeks duration. Presented at the American Heart Association Scientific Sessions; Orlando, Florida; November 10, 2015; abstract 534.