The American Heart Association (AHA) Scientific Sessions 2016 was held in New Orleans, LA from November 12-16. The most interesting results were from PCSK9 inhibitors, with details from Repatha's positive atherosclerosis imaging study and Phase II data from inclisiran confirming the possibility of very prolonged dosing. Other studies on IV iron Injectafer and anticoagulant Xarelto could help bolster use of the drugs in particular segments of patients, though there were still lingering questions. Cardiologists we spoke with also had a great deal of enthusiasm for the SGLT-2 inhibitors in diabetic patients with CV disease due to Jardiance's EMPA-REG results, which were highlighted in one session. On the device front, HeartMate 3 encouragingly performed better than the previous-generation left ventricular assist device on short-term outcomes, though since this was only due to less pump malfunction, longer-term data from the study will be needed to see if there are any other advantages. The bullets below provide highlights from these and other presentations. Dyslipidemia

• Details from PCSK9 inhibitor Repatha's (AMGN) atherosclerosis imaging study GLAGOV were encouraging, with some data suggesting continued improvement at quite low LDL-C levels.
• Phase II data from inclisiran (MDCO, ALNY), an RNAi PCSK9 synthesis inhibitor, bolstered company plans for dosing 2-3 times per year, though longer follow-up is needed for confirmation. There was only a modest drop-off in efficacy after 180 days for the anticipated dose to take forward.
• Failure of high-density lipoprotein mimetic MDCO-216 (MDCO, PFE) in an atherosclerosis imaging study raises questions for similar products, like CSL112 (CSL Limited), which had data on safety and cholesterol efflux at the conference.
• Early-stage data on ANGPTL3 inhibitors evinacumab (REGN) and IONIS ANGPTL3-LRx (IONS) showed large reductions in triglycerides, but only modest LDL-C lowering.
  • In evinacumab's single-dose study, stronger reductions in triglycerides were only seen for IV doses 5mg/kg or higher, and given the limitations of concentrating monoclonal antibodies, company officials would not yet say what type of subcutaneous delivery they would use to accommodate such higher doses or whether multiple lower doses could suffice.
    • There were also a couple of safety considerations that will need to be investigated further: liver enzyme elevations and a rebound effect for triglycerides with the subcutaneous doses.
  • While a broad lipid indication for such drugs would undoubtedly require CV outcomes trials, with uncertain results, an IONIS investigator mentioned other indications they may pursue, including homozygous FH patients needing apheresis, patients with very high triglyceride levels, and those with hepatic steatosis or NASH.

Heart Failure

• The IV iron Injectafer (Daiichi, Fresenius, Galenica, Zenia) showed a benefit on peak oxygen consumption in heart failure patients with reduced ejection fraction and iron deficiency, but independent of whether patients had anemia.
  • The results complemented other trials in the indication which the company hopes will expand usage of the drug.
  • The case for the drug was bolstered by the failure of oral iron to do the same in IRONOUT HF, also presented at the conference.
  • However, larger outcomes trials may be needed for any label or guideline changes that would result in broader use in non-anemic patients.
• The vasodilator ularitide (Cardiorentis, PDLI, Pharis) failed to show any signs of a benefit on its composite primary outcome or CV death, despite some signals for improvement of decongestion and early heart failure events.
  • The investigators concluded that signs of early benefit apparently were unable to reduce myocardial injury or change the long- term natural history, which raises the risk for NVS's Reasanz, whose pivotal results are expected in 2017.
• In the short-term segment of its IDE trial against the earlier-generation left ventricular assist device, HeartMate 3 (STJ) did show a benefit on the primary outcome, but this was only due to a reduction in reoperation for pump malfunction (eg from thrombosis) and, somewhat disappointingly, without an appreciable difference on other components of the composite outcome, disabling stroke or death. However, the study continues to evaluate longer-term outcomes for destination therapy.

Anticoagulation and Antiplatelet Therapy

• Xarelto (JNJ, BAYRY) had encouraging bleeding results in PIONEER AF-PCI, which studied the segment of atrial fibrillation patients who require PCI with stent placement. However, the question of whether the use of lower doses came at the expense of less stroke prevention was not definitively answered, leading to differences in opinion about the findings.
• Details from Brilinta's (AZN, MDCO) failed trial in peripheral arterial disease showed no signs of a benefit over clopidogrel, and investigators did not have a good explanation. The drug did perform better in subgroups with a history of coronary revascularization or stents, consistent with its approved indications.
  • The failure was another big disappointment for AZN following the failure of the drug's stroke trial, but there is still some hope for a trial of type 2 diabetics, where there is only a placebo comparator.

CV Outcomes Trials (CVOTs) of Diabetes Drugs

• A session on the CVOTs of diabetes drugs was timely given FDA approval of SGLT-2 inhibitor Jardiance for reducing CV death soon after the conference. There was a great deal of enthusiasm, particularly about the SGLT-2 inhibitors, at the conference, and several cardiologists we spoke with expected to take a more active role in recommending the use of SGLT-2 inhibitors to the primary diabetes physician.
  • We gauged primary care views on the diabetes CVOTs in a recent survey and interview, which are part of our KOL Insight service.

This report also includes news or data on other drugs and topics, such as: data on the usage of PCSK9 inhibitors, neprilysin inhibitor TD-0714 (Theravance), anticoagulants betrixaban (PTLA) and VE 1902 (Verseon), and PAD cell therapy MarrowStim (ZBH). Like our report? Have any questions or feedback? Please let us know at askanalyst@sagientresearch.com.

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