Cardiac Drugs - The Missing Links (Drugs we should have in New Zealand)

Transcription

1 Pharmac: Devices and Drugs Heart drugs the missing links John Elliott Chairs: Rob Doughty & Rajesh Nair Cardiac Drugs - The Missing Links (Drugs we should have in New Zealand) John Elliott University of Otago Christchurch Christchurch Hospital Conflicts of Interest Clinician Scientist Principal Site Investigator in many international pharmaceutical trials Member Cardiovascular Subcommittee of PTAC, Pharmac. Presented yesterday at sponsored Breakfast meeting Pick on 3 Missing Links Rosuvastatin Entresto PCSK9 Inhibitors Ivabradine 1

2 Pick on 3 Missing Links when were they approved by the FDA? Rosuvastatin 2003 Entresto 2015 PCSK9 Inhibitors 2015 Ivabradine 2015 Not discussing any unproven drugs Or the importance of exercise/lifestyle Rosuvastatin Statin approved by FDA in 2003 More potent than other statins No clinical endpoint studies vs placebo in CAD patients the 7 th statin JUPITER Primary prevention in men >50 and women>60 with increased CRP and 1 CV risk factor. Reduced CV events. Greatest benefit in those achieving LDL <1.8mmol/L METEOR delayed progression of carotid atherosclerosis ASTEROID regression of coronary atherosclerosis assessed by intravascular ultrasound 2

3 Rosuvastatin 3 years ago in Australia (2015) Of 29,022 prescriptions for lipid modifying agents 11,856 Atorvastatin 9537 Rosuvastatin 4285 Sinvastatin 1229 Ezetimibe Brewer Am J Cardiol (4) (Suppl) 23K-29K Minutes of Cardiovascular Subcommittee of PTAC Rosuvastatin is a new medication not as many studies conducted lower risk subgroups with surrogate endpoints.. Limited evidence that rosuvastatin may have a role in patients who were intolerant of other statins If cost neutral to atorvastatin, consider criteria for rosuvastatin if LDL >2.5mmol/L on max tolerated dose of atorvastatin. Minutes of Cardiovascular Subcommittee of PTAC Rosuvastatin is a new medication not as many studies conducted lower risk subgroups with surrogate endpoints.. Limited evidence that rosuvastatin may have a role in patients who were intolerant of other statins If cost neutral to atorvastatin, consider criteria for rosuvastatin if LDL >2.5mmol/L on max tolerated dose of atorvastatin. Limp wristed 3

4 FDA News Release - April 29, For Immediate Release FDA approves first generic Crestor The U.S. Food and Drug Administration today approved the first generic version of Crestor (rosuvastatin calcium) tablets for the following uses: in combination with diet for the treatment of high triglycerides (hypertriglyceridemia) in adults; in combination with diet for treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia), a disorder associated with improper breakdown of cholesterol and triglycerides; either alone or in combination with other cholesterol treatment(s) for adult patients with homozygous familial hypercholesterolemia, a disorder associated with high low-density lipoprotein (LDL) cholesterol. FDA News Release - April 29, For Immediate Release FDA approves first generic Crestor The FDA is working hard to get first-time generic drugs approved as quickly as possible so patients can have increased access to needed treatments, said Kathleen Uhl, M.D., director of the Office of Generic Drugs in the FDA s Center for Drug Evaluation and Research. The FDA requires that generic drugs meet rigorous scientific and quality standards. FDA approved generic rosuvastatin 2 years ago But in New Zealand we wait Currently available for $1 a day No process for facilitating or inviting submissions Does that matter? 4

5 ARE WE REACHING TARGET LDL-CHOLESTEROL LEVELS IN PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROMES (ACS)? John M Elliott, Rachel M Elliott, Lorraine Skelton, Chris Frampton, A Mark Richards. Department of Medicine, Christchurch School of Medicine and Health Sciences CSANZ Auckland 2006 One year after admission for ACS, - 89% were still receiving a statin but only - 62% had had LDL-C levels retested and - 71% had LDL-C levels <2.5mmol/L - only 39% had LDL-C levels <2.0mmol/L. Rosuvastatin We need more lipid lowering agents in New Zealand Why cant we have subsidised access to a generic statin that happens to be the most potent And its cheap, even in Australia Trends in Australian Expenditure on CV Drugs Trends in Australian Expenditure on CV Drugs 5

6 Trends in Australian Expenditure on CV Drugs Entresto (Sacubitril and Valsartan) Sacubitril inhibits neprilysin which is an endopeptidase that normally breaks down natriuretic peptides, bradykinin and adrenomedullin Increases circulating natriuretic peptides Vasodilation and lower blood pressure PARADIGM HF Study (Entresto) Participants with heart failure (New York Heart Association class II-IV) due to reduced LVEF ( 40%) Randomized to LCZ696 (Entresto) 200 mg twice daily (n = 4,187) versus enalapril 10 mg twice daily (n = 4,212) in addition to standard therapy. Concomitant Medications: Digitalis: 29%, Betablocker: 93%, Mineralocorticoid antagonist: 54% 6

7 PARADIGM HF Study (Entresto) PARADIGM HF Substudy Okumura et al Methods and Results We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose ( 50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. Conclusions The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or β- blocker dose. Circulation: Heart Failure. 2016;9:e Originally published September 12, 2016 Entresto approved in other countries UK NICE March 2016 Canada March 2016 Australia July 2017 Republic of Ireland December 2017 Approved in 37 European countries NB PARADIGM HF published 2014 NEW ZEALAND GAZETTE, No NOVEMBER 2016 Pursuant to section 20 of the Medicines Act 1981, the Minister of Health hereby consents to the distribution in New Zealand of the new medicines set out in the Schedule hereto: Schedule Product: Entresto 24/26 Active Sacubitril/valsartan 50mg equivalent to 24.3mg Ingredient: sacubitril and 25.7mg valsartan Dosage Form: Film coated tablet New Zealand Novartis New Zealand Limited Sponsor: Novartis Pharma Stein AG, Stein, Switzerland Manufacturers: Novartis Singapore Pharmaceutical Manufacturing Pte Limited, Singapore 7

8 Entresto Australian PBS July 2017 Authority Required Chronic heart failure Clinical criteria: Patient must be symptomatic with NYHA classes II, III or IV, AND Patient must have a documented left ventricular ejection fraction (LVEF) of less than or equal to 40%, AND Patient must receive concomitant optimal standard chronic heart failure treatment, which must include the maximum tolerated dose of a beta-blocker, unless contraindicated or not tolerated, AND Patient must have been stabilised on an ACE inhibitor at the time of initiation with this drug, unless such treatment is contraindicated according to the TGA-approved Product Information or cannot be tolerated; OR Patient must have been stabilised on an angiotensin II antagonist at the time of initiation with this drug, unless such treatment is contraindicated according to the TGA-approved Product Information or cannot be tolerated, AND The treatment must not be co-administered with an ACE inhibitor or ARB. PTAC Meeting February Entresto PTAC Meeting February Entresto PTAC Meeting February Entresto Aim was Enalapril 10mg bd, average achieved dose was 18.9mg/day (Letter to Editor, Dec 2014) In New Zealand we have not used trial proven ACE inhibitor for 20 years Our use of ARB s is limited Comparison of new agent vs Enalapril scientifically valid 8

9 PTAC Meeting February Entresto But PARAGON-HF is testing Entresto in HFpEF patients Subsequent Cardiovascular Subcommittee Meetings One 6 months later in September Frustrations expressed No meeting of Cardiovascular Subcommittee planned for 2018 There will be further delays through Subcommittee and PTAC approvals Result is delay in possible funding till 2019 PARADIGM HF (Entresto) PARADIGM HF (Entresto) New Zealanders are still 2014 on the placebo curve 2018 Days since proof of benefit 9

10 PCSK9 Inhibitors Large body of evidence that they lower LDL cholesterol levels either alone or when added to max tolerated dose of statin Large body of evidence that they reduce CV endpoints. Alirocumab ODYSSEY studies, ODYSSEY OUTCOMES Evolocumab FOURIER studies ODYSSEY OUTCOMES ODYSSEY OUTCOMES mmol/l 10

11 ODYSSEY OUTCOMES ODYSSEY OUTCOMES >2.6 mmol/l PCSK9 Inhibitors In New Zealand in 2018 PCSK9 Inhibitors In New Zealand in 2018 We wait 11

12 Now 2018 How long will New Zealanders follow the placebo curve PHARMAC MODEL Effectively lowered prices paid for patented drugs Saved New Zealand money But New Zealanders have paid a price PHARMAC MODEL Effectively lowered prices paid for patented drugs, Saved New Zealand money But New Zealanders have paid a price Delayed access or no access to drugs with proven benefits in NZ Given the diverging curves in the CV endpoint studies, the effects of these delay will be magnified over time We continue to live on the placebo curve ? 12

13 Does that matter? Inequities Inequities between nations New Zealand s health affected by political decisions I don t want to continue living on the placebo curve PHARMAC MODEL Effectively lowered prices paid for patented drugs, Saved New Zealand money But New Zealanders have paid a price Delayed access or no access to drugs with proven benefits in New Zealand Given the diverging curves in the CV endpoint studies, the effects of these delay will be magnified over time We continue to live on the placebo curve 13