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alirocumab (Praluent)

Indications: - coronary artery disease - lowers risk major adverse cardiovascular events (1.7% vs 3.3%) RR=0.52 - lowers risk of cardiovascular mortality or cardiovascular event within 3 years of acute coronary syndrome (15%) [9,10]* - familial hypercholesterolemia (FDA approved July 2015) [4,5] - secondary prevention of cardiovascular events [12] FDA-approved April 2019 - statin intolerant, LDL cholesterol above goal, taking ezetimibe * addition to high-intensity statin [9,10] Dosage: - 75 or 150 mg SQ biweekly Adverse effects: - itching, swelling, pain, bruising at the injection site - nasopharyngitis - flu-like syndreom - hypersensitivity reactions requiring hospitalization - hypersensitivity vasculitis [5] - reportedly, no increased risk of peripheral neuropathy, cognitive impairment, or diabetes complications with LDL cholesterol levels < 25 mg/dL [7] - cataracts [7] - antidrug antibodies (5.1% vs 1.0% for placebo) - patients with antidrug antibodies still with lowering of LDL cholesterol & without apparent adverse reactions other then more frequent injection site reactions [8] - increased risk of new onset diabetes mellitus type 2 (absolute risk 0.9%) [13] Drug interactions: - in combination with statin [2] - increases risk of myalgia (5.4% vs 2.9%) - increases risk of neurocognitive events (1.2% vs 0.5%) - increases risk of ophthalmologic events (2.9% vs 1.9%) Mechanism of action: - PCSK9 inhibitor - average reduction in LDL cholesterol ranging 36-59 mg/dL vs placebo [5] - lowers LDL cholesterol in patients taking statin - lowers Lp(a) [13] Clinical trials: - post-hoc analysis of Odyssey long-term - alirocumab reduces cardiac death, myocardial infarction, & unstable angina requiring hospitalization (1.4 vs 3% for placebo) [1] - no established differences in health outcomes relative to statins alone [3] Notes: - available at list price of $5850 a year for the 75 mg & 150 mg doses beginning in early March 2019 [11]

Interactions

drug adverse effects of anti-hyperlipidemic agents

General

PCSK9 inhibitor (ALN-PCS) pharmaceutical monoclonal antibody

References

  1. Physician's First Watch, Sept 2, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief News from the European Society of Cardiology Congress. Massachusetts Medical Society http://www.jwatch.org
  2. Robinson JG et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015 Mar 15; PMID: 25773378 http://www.nejm.org/doi/full/10.1056/NEJMoa1501031
  3. Husten L, Di Francesco S Success of Two New Cholesterol Drugs May Come Down to Convenience, Dosing, and Cost. Physician's First Watch, May 27, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  4. Young K, Saitz R FDA Advisers Recommend First-in-Class Cholesterol-Lowering Meds Physician's First Watch, June 11, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - FDA Briefing Document BLA 125559. June 9, 2015 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM449865.pdf
  5. Brauser D FDA Approves New LDL-Lowering Agent Alirocumab (Praluent). Medscape Oncology. July 24, 2015 http://www.medscape.com/viewarticle/848535 - FDA News Release. July 24, 2015 FDA approves Praluent to treat certain patients with high cholesterol. First in a new class of injectable cholesterol- lowering drugs http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455883.htm
  6. Prescriber's Letter 22(8): 2015 PCSK9 Inhibitors for High Cholesterol Detail-Document#: 310813 http://www.prescribersletter.com (subscription needed)
  7. Robinson JG, Rosenson RS, Farnier M Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab. Pooled Data From Randomized Trials. J Am Coll Cardiol 69(5) Feb 2017 PMID: 28153102 Free Article http://www.onlinejacc.org/content/69/5/471 - Everett BM Low-Density Lipoprotein Cholesterol and the On-Target Effects of Therapy. How Low Is Too Low? J Am Coll Cardiol 69(5) Feb 2017 PMID: 28153103
  8. Roth EM, Goldberg AC, Catapano A et al. Antidrug antibodies in patients treated with alirocumab. N Engl J Med 2017 Mar 17 PMID: 28304229
  9. Wendling P ODYSSEY Outcomes: Alirocumab Cuts CV Events, All-Cause Death Post-ACS. Medscape - Mar 10, 2018. https://www.medscape.com/viewarticle/893754 - ClinicalTrials.gov ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab. https://clinicaltrials.gov/ct2/show/NCT01663402
  10. Schwartz GG, Steg G, Szarek M et al Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. Nov 7, 2018 PMID: 30403574 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1801174
  11. Wendling P Second Price Cut for PCSK9 Inhibitor Alirocumab (Praluent). Medscape - Feb 12, 2019. https://www.medscape.com/viewarticle/908990
  12. Regeneron News Release. April 26, 2019 FDA Approves Praluent (alirocumab) to Prevent Heart Attack, Stroke and Unstable Angina Requiring Hospitalization. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-praluentr-alirocumab-prevent-heart-attack-stroke
  13. Brooks M Lp(a) Lowering With Alirocumab Tied to Small Increase in Risk of Type 2 Diabetes. Medscape - Apr 01, 2021 https://www.medscape.com/viewarticle/948542 - Schwartz GG, Szarek M, Bittner VA Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment. Diabetes Care 2021 Mar; dc202842. PMID: 33722880 https://care.diabetesjournals.org/content/early/2021/03/10/dc20-2842