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2016 Biomedtracker / Datamonitor / Meddevicetracker Post-ACC Report

May 02, 2016

The American College of Cardiology 65th Annual Scientific Session was held in Chicago, IL from April 2–4, 2016. The biggest news was in the device space, where the Sapien TAVR franchise (EW) was shown to be at least as good as surgery in intermediate-risk patients, with signs of superior outcomes, at least in certain groups. There was also data from a study of the PCSK9 inhibitor Repatha (AMGN) in patients screened for “true” statin intolerance, which serves as a springboard for discussions on reimbursement issues facing the class. Reimbursement and usage were also interesting topics at the conference for Entresto (NVS). In addition, there were a couple of major failed trials which had important implications for other drugs. The bullets below provide highlights from these and other presentations. Dyslipidemia
  • Repatha’s (AMGN) GAUSS-3 study used a cross-over screening period to determine which patients with a history of statin intolerance were truly intolerant to a statin and not placebo, before being randomized to Repatha or Zetia (ezetimibe). Only 42.6% passed this initial screening, though as expected, most who did performed well without such symptoms on Repatha, with a stronger LDL-C reduction than Zetia.
    • Physicians at the meeting noted that, in the US, prior authorization for the PCSK9 inhibitors is quite difficult, with many who fit the approved indications denied. However, most requests fitting the criteria can ultimately be approved with documentation and persistence.
    • How CV outcomes studies impact reimbursement will depend on the magnitude of the benefit, though barriers are likely to remain, such as prior authorization for failing statin and ezetimibe treatment, and high co-pays.
    • The report also notes the reimbursement situation in Europe.
  • A new ACC Expert Consensus Decision Pathway on the role of non-statins, including the PCSK9 inhibitors, was presented at the meeting and published.
    • Interestingly, the document brought back some LDL-C absolute level thresholds that had controversially been discarded in the 2013 ACC/AHA guidelines, though it avoided calling these targets.
    • The guidelines state PCSK9 inhibitors are “reasonable to consider” in ASCVD (atherosclerotic cardiovascular disease) patients unless they are fully statin-intolerant, in which case they are to be strongly considered. However, the document also acknowledged the difficulty in figuring out which patients are truly statin-intolerant.
  • Details from the failed trial of CETP inhibitor evacetrapib (LLY) showed little sign of a benefit despite strong HDL-C and LDL-C lipid changes. There was a trend towards reduced all-cause mortality, but without support from other endpoints, this may well have been due to chance.
    • Blood pressure and C-reactive protein were modestly increased, but did not appear to fully account for the failure of the trial.
    • While anacetrapib’s (MRK) CVOT is three times larger than ACCELERATE and also longer, without a signal from evacetrapib, hopes are not high for the trial, as it may well be the mechanism itself that is faulty. Given the latter, the PCSK9 inhibitors are still expected to succeed.
  • Crestor’s (AZN) HOPE-3 arm demonstrated an outcomes benefit in intermediate-risk patients without cardiovascular disease and without mandated specific lipid or blood-pressure levels. The benefit was also seen in a group with lower LDL-C levels, potentially supporting the risk- based approach used in the 2013 ACC/AHA guidelines, rather than prior higher LDL-C goals.
Transcatheter Valve Replacement (TAVR/TAVI and TMVR/TMVI)
  • Encouraging data from two studies on the Sapien franchise in intermediate-risk patients were presented, showing signs of superiority over surgery, at least in certain groups. Together, these should lead to label expansions for Sapien 3 and the older generation Sapien XT, as well as accelerating an existing trend of expanding treatment beyond those with high risk.
    • Patients in the studies were still on average 82 years old, so durability will be an important issue for expansion to younger, lower- risk patients.
    • Longer follow-up is still needed to evaluate more paravalvular regurgitation with the Sapien valves than surgery.
Heart Failure
  • Neither the renin inhibitor Tekturna (NVS) nor a combination of Tekturna and ACE inhibitor enalapril showed an outcomes benefit over enalapril alone, with safety issues for the combination.
    • While disappointing, the results highlight the strength of NVS’s ARB/NEP inhibitor Entresto, which bested enalapril in its pivotal CVOT, and counter the argument that Entresto succeeded merely due to better RAS (renin-angiotensin system) blockade.
  • Entresto had subgroup data on benefits in stable Class II patients and in combination with various background medications, but the biggest issues were reimbursement and other clinical considerations, raised at various venues.
    • The drug has had disappointing initial sales, with physicians at the conference complaining about time-consuming prior authorization and co-pays.
    • Cost-effectiveness data presented at the conference showed it would be considered cost-effective under conventional “willingness- to-pay” thresholds. While a couple outcomes-based reimbursement contracts are being tested, offsetting cost savings would not be as applicable to Medicare Part D stand-alone plans.
    • Currently, the drug is more broadly covered, which along with guideline recommendations should help revenues to pick up. Nevertheless, reimbursement barriers are likely to remain due to payer concerns about cost if use is widespread. The report notes revenue projections.
  • The autologous, processed stem cell product Ixmyelocel-T (VCEDL) met its primary outcomes endpoint, but details also raised questions, since there was no benefit on certain secondary endpoints.
  • After the conference, Bayer confirmed that the mineralocorticoid antagonist finerenone has been suspended in heart failure. We note the reasons for the decision. The lack of a direct comparison with current mineralocorticoid antagonists in heart failure could have implications for how it will be viewed in the diabetic nephropathy indication.
Atrial Fibrillation
  • Cryoablation with Arctic Front cryoballoon catheters (MDT) was non-inferior to radiofrequency ablation with ThermoCool ablation catheters.
    • Cryoablation is a simpler and quicker procedure requiring less extensive training, and proponents hope the study will help move ablation procedures from more specialized centers. However, there is some debate on how much shorter fluoroscopy time may be with radiofrequency ablation, a potentially mitigating factor.
The report was written by analysts from Biomedtracker and Datamonitor Healthcare, with contributions from other Informa brands, including an overview of cardiovascular trials from Trialtrove.
Indications Covered: Atrial Fibrillation/Flutter
Cardiac Valve Surgery
Chronic Heart Failure - Reduced Ejection Fraction (Chronic HFrEF)
Dyslipidemia / Hypercholesterolemia

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