ODYSSEY Outcomes Results for Sanofi's Praluent to Lead Off ACC Meeting

The next round of competition between 2 powerful drugs to lower cholesterol will come March 10, 2018, when the annual American College of Cardiology (ACC) Scientific Session opens in Orlando, Florida. That’s when results from the ODYSSEY Outcomes trial will show whether Sanofi-Regeneron’s alirocumab (Praluent) has a superior cardiovascular (CV) benefit to Amgen’s evolocumab (Repatha).

ODYSSEY Outcomes took longer, but there’s speculation that the wait will be worth it, if the data show the powerful class of injectable therapy, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, also produce significant CV benefits alongside their ability to reduce low-density lipoprotein (LDL) cholesterol by up to 60%. Both are approved to be used with maximally tolerated statins in patients with atherosclerotic CV disease and familial hypercholesterolemia (FH), a genetic condition.

The trial results from ODYSSEY Outcomes will “define the role of PCSK9 inhibition in cardiovascular medicine,” said Deepak L. Bhatt, MD, MPH, FACC, associate editor of ACC.org, in the article, “Trends for 2018: What’s Ahead in Our Journey in Cardiovascular Medicine?” which appears today on acc.org.

The ODYSSEY Outcomes results will come nearly a year after the last ACC meeting, where results from FOURIER showed Repatha had a modest CV benefit—a 15% reduction in a composite primary endpoint, with no reduction in CV death. Despite a 27% reduction in heart attacks and a 21% reduction in strokes over 2 years, analysts weren’t wowed and neither were payers.

Over the past year, physicians have told The American Journal of Managed Care^® they continue to face prior authorization hurdles when prescribing PSCK9 inhibitors, and a study published this month by Penn Medicine found the barriers are so high they raise questions whether patients with clear need—such as those with FH—are being unfairly denied access.

With ODYSSEY Outcomes due in a late-breaking session to kick off this year’s ACC meeting, Bhatt said, “Physicians are hoping there’ll be a greater degree of benefit in the ODYSSEY trial than was seen in the FOURIER trial.”

ODYSSEY is a smaller trial, with 18,000 patients compared with FOURIER’s 27,000, but it has a longer follow-up period, and a different composite endpoint, which could lead to different results. ODYSSEY Outcomes’ composite includes heart attacks, strokes, death from CV causes, and hospitalization for angina. FOURIER added coronary revascularization to the composite outcome.

“We are in a new era for the treatment of cholesterol,” said ACC.org editor-in-chief Kim A. Eagle, MD, MACC. As others have, Eagle cited the clinical results for PCKS9 inhibitors are being weighed against the costs—the drugs cost more than $14,000 a year. Several analyses have been published that say the drugs are not cost-effective at that price, including some that question the value for payers of Amgen’s offer of a money-back guarantee if patients have a heart attack while taking the drug.

Other highlights of the upcoming ACC meeting are featured in the article, including:

Anti-inflammatory drugs. A late-breaking trial on March 12, 2018, will feature results from the CANTOS trial, involving the anti-inflammatory canakinumab (Ilaris), including results in type 2 diabetes.

SGLT2 inhibitors. One of the biggest surprises of ACC 2017 was the results of the CVD-REAL trial, which suggested a role for these type 2 diabetes drugs in primary prevention of heart failure, and this year’s meeting will feature more results. “The overall impact of this class of drugs on cardiovascular outcomes and heart failure is striking,” said Douglas L. Mann, MD, FACC, editor-in-chief of JACC: Basic to Translational Science.

“The intersection of diabetes and cardiovascular disease will become more apparent,” adds Bhatt, noting the increased involvement of cardiologists treating patients with diabetes and obesity. “There’ll be increasing interest and focus on the evaluation of novel diabetes drugs in cardiovascular populations, examining potential benefits on the ischemic as well as heart failure endpoints.” (For more, see the December issue of Evidence-Based Diabetes Management™.)

Healthcare delivery. The biggest trend in CV care is the shift from episodic care to continuous care, a “culture shift” that Jagmeet Singh, MD, PhD, FACC, deputy editor of JACC: Clinical Electrophysiology believes will help control costs in the long run.

What is the key? “Data from wearable and implantable technology will be integrated into the electronic health record,” Singh says. Fueled by artificial intelligence, the data will promote interventions at the right time, using the tools of telemedicine and remote monitoring to reduce readmissions, with a major focus on heart failure and atrial fibrillation. Patient-enabled communications will promote better collaboration with physicians, but the doctor will be joined by a new member of the team: the health coach. Outcomes-based reimbursement will drive the need for trained personnel who motivate patients to stick with regimens to improve diabetes and obesity to reduce their CV risk.

“The CV team is operating in an environment of regulatory and payment change,” said Richard Kovacs,” MD, FACC, chair of ACC’s Science and Quality Committee. The rise of accountable care organizations, alternative payment models, and bundled payments are “requiring the CV team to adapt to the stuttering shift from volume to value.”

To thrive, he said, the CV team will be pushed, “outside our usual comfort zone.”