The American Heart Association (AHA) 2015 Scientific Sessions was held in Orlando, Florida from November 7 - 11, 2015. Much of the data from novel therapies at this year's AHA were incremental--or suggestive of further study but not definitive. Still, interesting information came out on various products that could help define the longer term competitive landscape in their indications. On the device side, major positive data on the Micra TPS leadless pacemaker was released. The most highly anticipated data at the conference was a reduction in mortality and MACE with intensive blood pressure control from the SHIFT trial, though a number of drugs, including generics, were used. Additional subgroup analysis from diabetes drug Jardiance's CV outcomes trial was also quite interesting. Highlights from this year’s meeting include: Dyslipidemia

• Updated Phase I data on ALN-PCSsc (MDCO, ALNY) reinforced company hopes that the RNAi PCSK9 inhibitor could be given semi-annually, at least in a number of patients.
  • The ORION 1 Phase II study will also look at quarterly dosing, which officials said is particularly important for Europe, to go along with quarterly LDL-c checks.
  • Confirmation is still needed on the company's claim that a waning of LDL-c reduction with the 300 mg dose in patients on statins is just random variability, given continued suppression of PCSK9. However, a monoclonal antibody investigator believes the somewhat lesser LDL-c reduction, albeit with a long duration of action, was what might be expected, given the lesser PCSK9 suppression compared to mAbs.
• Only incremental data was released on ETC-1002, but ESPR officials acknowledged more the "dynamic regulatory environment" and possibility the drug could need a CV outcomes trial prior to approval.
  • All eyes are on Vytorin's (MRK) IMPROVE-IT adcom in December and its implications for ETC-1002 and others.
    • While overall results showed an outcomes benefit consistent with the overall LDL-c lowering, supporting LDL-c as a general surrogate, subgroup analyses have shown the effect to be concentrated in certain high risk groups--though it is not clear how much of an issue this will be at the adcom meeting.
    • A risk score for deciding which patients are most appropriate for Vytorin/Zetia was not presented at the AHA, as investigators had suggested in the past. Interestingly, though, they reportedly will use the same scoring system that was presented at the AHA for Zontivity's (MRK) TRA 2°P - TIMI 50 and report results in early 2016.
• As expected, ISIS-APO(a)-LRx (ISIS) demonstrated a strong reduction in Lp(a) in a Phase I study, though with fewer injection site reactions using the new LICA technology. The company believes dosing could be quarterly or even less frequent.
  • The major question is still whether FDA will approve the drug without outcomes trial (other than for calcific aortic valve stenosis), but company officials are hopeful it can be.

Heart Failure

• Vericiguat (MRK, BAYRY), a guanylate cyclase stimulator, missed its primary endpoint in Phase II study of patients with worsening heart failure, though there were still signals of a benefit for the high dose, including lower heart failure hospitalization and death.
  • The latter are intriguing, though quite tentative, and worthy of further study.
• Details from omecamtiv's (AMGN, CYTK) Phase II COSMIC-HF showed consistent improvements on a number of measures.
  • Whether changes in echo measures should translate into a sufficient clinical benefit depends on what comparisons are made (eg graphs from a company- associated KOL are shown), but the reduction in NT-proBNP along with these other improvements is encouraging.
• One-year results from Algisyl-LVR's (LoneStar) AUGMENT-HF trial showed a continued increase in functional benefits and numerical reduction in worsening heart failure, but was marred by a numerical increase in cardiovascular death. Further study of the injected polymer device is needed to see if the latter was due to chance.
• The investigator initiated study (BEAT-HF) of the ß3-adrenoceptor agonist Myrbetriq (Astellas) in heart failure failed to show improvement on the primary endpoint, but investigators are pursuing another study due to a signal for a benefit in patients with more severe disease.

Diabetes Drugs and CV Indications

• Encouragingly, subgroup analysis from SGLT2 inhibitor Jardiance's (Boehringer, LLY) EMPA-REG CV outcomes trial showed patients without heart failure at baseline had at least as strong a reduction in a number of endpoints as those with heart failure.
  • It may be difficult to fully ascertain the mechanism and understand which patient groups benefit most, though there could be pressure from physicians to better understand that.
  • In a recent BMT pulse survey, a similar proportion said they would substantially increase use of Jardiance in those with atherosclerotic CV disease as in those with heart failure (some details provided below).
• GLP-1 agonist Victoza (NVO) fails to show a benefit in investigator initiated Phase II study of high risk heart failure patients.
  • There were signals of increased heart failure hospitalization and worsening renal function, though investigators are still evaluating data for the subgroup with diabetes. More definitive data should come from LEADER CVOT in a broader spectrum of heart failure.

Stroke Prevention in Atrial Fibrillation (SPAF)

• Positive, albeit expected, results were shown for andexanet's (PTLA) reversal of Xarelto with a 2-hour infusion, but is the infusion long enough in emergency situations?

Acute Coronary Syndrome and Coronary Artery Disease

• Risk scores identified for selecting most appropriate patients for prolonged dual antiplatelet therapy (DAPT trial) and MRK's Zontivity (TRA 2°P - TIMI 50 trial).

Dysrhythmia

• Positive final results were released for the Micra TPS (MDT) leadless pacemaker, though the data appears comparable to that released at the ESC from St. Jude's Nanostim.

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