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Praluent to prevent myocardial infarction, stroke and unstable angina requiring hospitalization, approved by FDA

The FDA ( U.S. Food and Drug Administration ) has approved Praluent ( Alirocumab ) to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.

High levels of low-density lipoprotein cholesterol ( LDLC ) increase patients’ risk for serious cardiovascular events. Adults who experience a myocardial infarction or stroke have an approximately one in three chance to have another cardiovascular event.

The FDA approval is based on data from ODYSSEY OUTCOMES, which was published in the New England Journal of Medicine ( NEJM ) in November 2018, assessing the effect of adding Praluent to maximally-tolerated statins on cardiovascular outcomes in 18,924 patients who had an acute coronary syndrome ( ACS ) within a year of enrolling in the trial.
Patients who received Praluent in the trial experienced:

• a 15% reduced risk for major cardiovascular events. The primary endpoint included time to first myocardial infarction, stroke, death from coronary heart disease ( CHD ), or unstable angina requiring hospitalization ( hazard ratio, HR=0.85; 95% CI, 0.78 to 0.93; p=0.0003 );

• a 27% reduced risk of stroke, 14% reduced risk of non-fatal myocardial infarction and 39% reduced risk of unstable angina requiring hospitalization;

• a 15% reduced risk of death from any cause ( HR=0.85; 95% CI, 0.73 to 0.98; nominal p=0.026 ).

Adverse events were similar between the Praluent and placebo groups, except for injection site reactions ( Praluent 3.8%, placebo 2.1% ).
In ODYSSEY OUTCOMES, the adverse events that occurred in more than 5% of patients included: non-cardiac chest pain ( 7.0% Praluent, 6.8% placebo ), nasopharyngitis ( 6.0% Praluent, 5.6% placebo ) and myalgia ( 5.6% Praluent, 5.3% placebo ).

The FDA has also approved Praluent as an adjunct to diet, alone or in combination with other lipid-lowering therapies ( e.g., statins, Ezetimibe ), for the treatment of adults with primary hyperlipidemia ( including heterozygous familial hypercholesterolemia ) to reduce LDL-C.

Praluent is the only PCSK9 inhibitor available in two doses with two levels of efficacy as a single 1 mL injection ( 75 mg and 150 mg ) once every two weeks.
It can also be administered as 300 mg once every four weeks ( monthly ), enabling physicians to tailor treatment based on an individual patient’s LDL-C-lowering needs.

ODYSSEY OUTCOMES, the longest cardiovascular outcomes trial of any PCSK9 inhibitor to date, has assessed the effect of Praluent on the occurrence of major adverse cardiovascular events in patients who had experienced an acute coronary syndrome before enrolling in the trial, and who were already on intensive or maximally-tolerated statin treatment.
Patients were randomized to receive Praluent ( n=9,462 ) or a placebo ( n=9,462 ) and were assessed for a median of 2.8 years, with some patients being treated for up to five years.
Approximately 90% of patients were on high-intensity statins prior to randomization.
The trial was designed to maintain patients' LDL-C levels between 25-50 mg/dL ( 0.65- 1.29 mmol/L ), using two different doses of Praluent ( 75 mg and 150 mg ).
Praluent-treated patients started the trial on 75 mg every two weeks and switched to 150 mg every two weeks if their LDL-C levels remained above 50 mg/dL ( n=2,615 ).
Some patients who switched to 150 mg switched back to 75 mg if their LDL-C fell below 25 mg/dL ( n=805 ), and patients who experienced two consecutive LDL-C measurements below 15 mg/dL ( 0.39 mmol/L ) while on the 75 mg dose ( n=730 ) stopped active Praluent therapy for the remainder of the trial. ( Xagena )

Source: Sanofi, 2019