Like the basketball Atlantic Coast Conference, the other ACC, the American College of Cardiology, ramps up this time of year with its annual scientific session.

Drug companies large and small presented data at the 64th version of the heart conference.

LAYUP

Astrazeneca plc's antithrombotic agent Brilinta (ticagrelor) was approved in 2011, based on PLATO, a nearly 20,000 patient trial, so running another trial with similar results shouldn't have been particularly challenging for the London-based pharma.

PLATO (A Study of PLATelet Inhibition and Patient Outcomes) compared Brilinta to Plavix (clopidogrel, Bristol-Myers Squibb Co. and Sanofi SA) in patients with acute coronary syndromes (ACS), but there were regional imbalances, with patients in North America performing worse than the rest of the world.

The PEGASUS-TIMI 54 (PrEvention with TicaGrelor of SecondAry Thrombotic Events in High-RiSk Patients with Prior AcUte Coronary Syndrome – Thrombolysis In Myocardial Infarction Study Group) trial tested Brilinta plus low-dose aspirin compared to low-dose aspirin alone to see whether the drug could help patients who had experienced a heart attack one to three years prior to study enrollment.

Brilinta significantly reduced the primary composite endpoint of cardiovascular death, myocardial infarction or stroke compared to placebo (7.85 percent in the Brilinta 90-mg arm, 7.77 percent in the Brilinta 60-mg arm, and 9.04 percent in the placebo arm).

"Following full presentation of the data this weekend at the ACC meeting in San Diego, the benefits of PEGASUS include confirmation of the drug's efficacy, putting to bed PLATO's regional inconsistencies," Leerink analyst Seamus Fernandez wrote in a note to clients.

Unfortunately, in addition to the reduction in cardiovascular outcomes, Brilinta also increased the rate of bleeding (TIMI Major bleeding at three years of 2.6 percent in the Brilinta 90-mg arm, 2.3 percent in the Brilinta 60-mg arm, and 1.06 percent in the placebo arm), which was fairly consistent with previous trials.

Fernandez said he believes the data, especially the "marginal benefit" from the 60-mg dose, are unlikely to substantially increase cardiologists' prescriptions of Brilinta over the other antithrombotic agents. "We view the full results of the PEGASUS trial as supportive of higher Brilinta sales, but unlikely to drive upside to our $3 billion peak sales estimate."

CINDERELLA STORY?

Actelion Ltd. is hoping to take down the number one seed in the pulmonary arterial hypertension (PAH) market, Silver Spring, Md.-based United Therapeutics Corp.

At ACC, Allschwil, Switzerland-based Actelion presented long-term outcome data from the pivotal phase III trial testing Uptravi (selexipag) in patients with PAH. If approved, Uptravi would compete with United Therapeutics' Orenitram (treprostinil), and the inhaled version, Tyvaso.

Uptravi significantly reduced the risk of a morbidity and mortality event by 40 percent vs. placebo (p<0.0001) and increased the distance patients could walk in six minutes after 26 weeks of treatment by 12 meters compared to placebo (p=0.0027).

Patients in the trial were allowed to be on background therapy of an endothelin receptor antagonist (ERA), a phosphodiesterase-5 inhibitor (PDE-5) or both. The results were consistent irrespective of background therapy.

But Evercore ISI analyst Mark Schoenebaum pointed out only one group really matters. "The key here is to look at data for patients who are on dual background therapy (i.e., both a PDE5 and ERA), as this is the standard of care today," he wrote in a note to clients. "While it is good that even in dual background therapy patients, there was indeed a benefit, it's puzzling that the benefit was similar to patients with no background therapy, which should have arguably had a larger benefit."

Schoenebaum also highlighted the lack of a statistically significant increase in six-minute walk test for patients on background therapy (a seven-meter increase for Uptravi compared to placebo, p=0.0929). "Actelion did not specifically breakout dual background six-meter walk data, which arguably would be worse than the seven meters," he wrote.

JUMP BALL

Amgen Inc. and partners Regeneron Pharmaceuticals Inc. and Sanofi SA are in a race to bring the first PCSK9 antibody to the market. Repatha (evolocumab) developed by Thousand Oaks, Calif.-based Amgen, has a PDUFA date of Aug. 27. Regeneron, of Tarrytown, N.Y., and Sanofi, of Paris, filed second, but were able to jump ahead using a priority voucher to accelerate the PDUFA for Praluent (alirocumab) to July 24.

At ACC and through accompanying NEJM articles, outcomes data were presented for both drugs, but they weren't much help in distinguishing the two drugs.

A pre-specified exploratory analysis for Amgen's open-label OSLER trials showed a lower rate of cardiovascular events (0.95 percent) in the evolocumab plus standard of care arm compared to the standard of care arm (2.18 percent, p= 0.003).

A post hoc analysis of Regeneron's and Sanofi's ODYSSEY LONG TERM trial showed major adverse cardiovascular events occurred in 1.7 percent of patients in the Praluent arm compared to 3.3 percent in the placebo group (p=0.02).

The small size of the trials, the open-label in Amgen's and the post hoc analysis for Praluent make for comparisons dangerous. Both companies have larger outcomes trials ongoing that should definitively confirm the decrease in cardiovascular events.

"The results are no doubt encouraging (and not all that surprising) but are also probably best viewed as directionally supportive given the relatively low number of events and wide confidence intervals," wrote JP Morgan analyst Cory Kasimov.

Based on the share price increases on the Monday following the ACC presentations (Amgen up 5.7 percent and Regeneron up 5.2 percent), investors appeared more focused on how the data are going to help boost sales of both drugs than which one will actually win the game.

TOO MANY MEN ON COURT

Stealth Biotherapeutics Inc.'s EMBRACE trial testing Bendavia (MTP-131) in patients with acute coronary syndrome (ACS) undergoing a myocardial infarction (MI) missed its primary endpoint of area-under-the-curve for creatine kinase MB, an enzyme used to estimate cardiac damage from an MI. The CK-MB was numerically lower (5570 ± 486 ng*h/mL vs. 5785 ± 426 ng*h/mL) in the Bendavia-treated patients, but the difference wasn't statistically significant.

When Stealth investigated further, the company realized there were more patients with hypertension in the placebo group than in the group that received Bendavia. The statistically significant imbalance of hypertensive patients appears to have moderated Bendavia's apparent efficacy.

"The therapy has the greatest potential in that patient population," Travis Wilson, Stealth's president and CEO, told BioWorld Insight.

An analysis of just the patients with hypertension showed significantly lower infarct volumes in patients that received Bendavia (35.8 mL) compared to those that received placebo (52.6 mL, p=0.03), consistent with reduced cardiac damage in the treated patients.

The Boston-based company is also testing Bendavia, which is designed to preserve energetics and restore normal energy production in mitochondria, as a chronic therapy in patients with kidney disease and heart failure.

If those trials are successful – Bendavia has already shown promise in acute kidney injury – Stealth is hoping to combine the two and treat heart failure patients with kidney disease as a co-morbidity, a population in need of treatments since many heart drugs are contraindicated for patients with kidney disease.