Zontivity (vorapaxar), Merck’s Cardio Drug Approval by FDA: Will it Challenge existing Oral Anticoagulation drugs: i.e., Apixaban, Dabigatran, Edoxaban, Rivaroxaban
Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 1/15/2019
“The number of clinical events in the study was modest, but the overall results were consistent with the main COMPASS study findings in suggesting that rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone will also reduce [MACE] major adverse cardiovascular events.”
- Guidelines currently recommend antiplatelet therapy after CABG with aspirin or clopidogrel (Plavix) to prevent graft failure and improve clinical outcomes.
COMPASS-CABG was a substudy of patients enrolled into the COMPASS trial within 2 weeks following CABG. Participants were randomized to aspirin 100 mg once daily (n=463) alone or in combination with rivaroxaban 2.5 mg twice daily (n=502), or to rivaroxaban alone at 5 mg twice daily (n=483).
Major bleeding in the first 30 days occurred at similar rates among groups (0.4% for rivaroxaban plus aspirin, 0.2% for rivaroxaban alone, and 1.1% for aspirin alone). None of these serious bleeding complications were fatal or led to reoperation or cardiac tamponade.
SOURCE
Journal of the American College of Cardiology
UPDATED on 8/16/2016
The presence of any VHD did not influence the comparison of Dabigatran [Pradaxa, Boehringer Ingelheim] with warfarin
It is important to note that similar to RE-LY, 14% of patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial and 26% of patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial had heart-valve disease other than prosthetic valve disease or significant mitral valve stenosis.
Two other post hoc analyses looked at outcomes with rivaroxaban (Xarelto, Bayer/Johnson) vs warfarin in the ROCKET-AF trial and apixaban ( Eliquis, Bristol-Myers Squibb/Pfizer) vs warfarin and in the ARISTOTLE trial—specifically in patients with valvular heart disease.
Taken together, “the evidence regarding the value of NOACs in patients with [valvular heart disease] as defined in the three studies is very strong” and is reflected in the recent European and American guidelines, according to Ezekowitz et al.
This analysis was sponsored by a research grant from Boehringer-Ingelheim Pharmaceuticals. Ezekowitz has served as a consultant for AstraZeneca, Eisai, Pozen, Boehringer Ingelheim, ARYx Therapeutics, Pfizer, Sanofi, Bristol-Myers Squibb, Portola, Daiichi Sankyo, Medtronic, Merck, Johnson & Johnson, Gilead,Janssen Scientific Affairs, and Armetheon. He has received grants from Boehringer Ingelheim, Bayer, Daiichi Sankyo, Pfizer, and Bristol-Myers Squibb. Disclosures for the coauthors are listed in the article.
SOURCE
Merck’s Statement
The U.S. Food and Drug Administration today approved Zontivity (vorapaxar) tablets to reduce the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore the blood flow to the heart in patients with a previous heart attack or blockages in the arteries to the legs.
Zontivity is the first in a new class of drug, called a protease-activated receptor-1 (PAR-1) antagonist. It is an anti-platelet agent, designed to decrease the tendency of platelets to clump together to form a blood clot. By decreasing the formation of blood clots, Zontivity decreases the risk of heart attack and stroke.
Like other drugs that inhibit blood clotting, Zontivity increases the risk of bleeding, including life-threatening and fatal bleeding. Bleeding is the most commonly reported adverse reaction in people taking Zontivity. The drug’s prescribing information (label) includes a Boxed Warning to alert health care professionals about this risk.
Zontivity must not be used in people who have had a stroke, transient ischemic attack (TIA), or bleeding in the head, because the risk of bleeding in the head is too great.
“In patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death. In the study that supported the drug’s approval, Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research.
Health care professionals should inform patients that they may bleed and bruise more easily when taking Zontivity. Patients should report to their health care professional any unanticipated, prolonged or excessive bleeding, or blood in their stool or urine. Zontivity will be dispensed with an FDA-approved patient Medication Guide that provides instructions for its use and important safety information.
In a clinical trial with over 25,000 participants, Zontivity, added to other anti-platelet agents (generally aspirin and clopidogrel), reduced the rate of a combined endpoint of heart attack, stroke, cardiovascular death, and urgent procedures to improve blood flow to the heart (coronary revascularization) when compared to an inactive pill (placebo).
Zontivity is made by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. of Whitehouse Station, N.J.
For more information:
- New drugs at FDA
- FDA approved drugs: Questions and Answers
- National Institute of Heart, Lung, and Blood Institute: What is Excessive Clotting?
Read more: FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients – FierceBiotech http://www.fiercebiotech.com/press-releases/fda-approves-zontivity-reduce-risk-heart-attacks-and-stroke-high-risk-patie#ixzz31LoiNGes
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SOURCE
FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients – FierceBiotech http://www.fiercebiotech.com/press-releases/fda-approves-zontivity-reduce-risk-heart-attacks-and-stroke-high-risk-patie#ixzz31LmW3uCv
Entrenched Competition to Zontivity (vorapaxar), Merck’s Cardio Drug Apixaban, Dabigatran, Edoxaban, Rivaroxaban
Coagulation Therapy: Leading New Drugs – Efficacy Comparison
Curator: Aviva Lev-Ari, PhD, RN
This article consists of a bibliography of Curations and Reporting on this topic by Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2014/05/10/coagulation-therapy-leading-new-drugs-efficacy-comparison/
Apixaban (Eliquis): Mechanism of Action, Drug Comparison and Additional Indications
Curator: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2014/05/10/apixaban-eliquis-mechanism-of-action-drug-comparison-and-additional-indications/
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Merck wins FDA approval for a once-vaunted cardio drug
The pill, to be marketed as Zontivity, is a first-in-class inhibitor of PAR-1, stopping the receptor from interacting with thrombin and thus halting platelets from forming blood clots. The drug is approved to reduce risk of heart attack, stroke and other cardiovascular events in patients who have already endured a heart attack or who have peripheral arterial disease. In its pivotal data submitted to the FDA, vorapaxar lowered stroke risk from 9.5% to 7.9% over three years, the agency said.
However, Merck’s cardio contender carries some serious bleeding risks, and the FDA has slapped a black-box warning on the drug to advise physicians of the potential for fatal episodes. As expected, vorapaxar is contraindicated for patients who have already had strokes or transient ischemic attack, excising a sizable patient population and dampening sales projections.
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The well-traveled treatment was a major factor in Merck’s $41 billion buyout of Schering-Plough back in 2009, singled out as a pill with a blockbuster future with the potential to beat out tried-and-cheap warfarin and notch peak sales of up to $5 billion a year. Within three years, however, serious bleeding risks came to light, leading Merck to leave out stroke patients from its FDA application and thereby trim some of vorapaxar’s potential market.
But the drugmaker remains confident its cardio drug has a bright commercial future. About 7.6 million Americans have suffered a heart attack, Merck has said, and about 190,000 eventually have a recurrent episode, creating a sizable unmet need.
Meanwhile, the Whitehouse Station, NJ, pharma giant is in the midst of an R&D realignment, which includes a renewed focus on cardiovascular therapies. Alongside the Phase III atherosclerosis drug anacetrapib, vorapaxar was the second late-stage pillar in Merck’s thin cardio pipeline, but the drugmaker has since struck up a deal worth up to $2.1 billion with Bayer, signing up to share rights to the pulmonary arterial hypertension treatment Adempas and collaborate on some in-development heart failure candidates.
– read the statement
Related Articles:
Merck pays $1B to buy into Bayer’s cardio future
Merck clears an FDA panel with its clot-fighting vorapaxar
Bleeding risk clouds Merck’s hopes for vorapaxar franchise
SOURCE
Merck wins FDA approval for a once-vaunted cardio drug – FierceBiotech http://www.fiercebiotech.com/story/merck-wins-fda-approval-once-vaunted-cardio-drug/2014-05-08#ixzz31LorKNEw
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