Medical World News: Managed Care Updates, December 2018

Oral Semaglutide Offers Superior A1C Reduction, Weight Loss in PIONEER 5 Trial

Novo Nordisk announced in August 2018 that topline results for its phase 3a trial of oral semaglutide show the drug reduced glycated hemoglobin (A1C) and helped patients with type 2 diabetes (T2D) lose weight after 26 weeks. If successful, the drug would be the first glucagon-like peptide-1 (GLP-1) receptor agonist taken once daily as a tablet.

PIONEER 5 is one of 10 trials involving the study drug. An injectable form of semaglutide, sold as Ozempic, received FDA approval¹ last year.

Results of the PIONEER 5 trial, which involved 324 people with T2D and moderate renal impairment, showed that those treated with 14 mg oral semaglutide saw an A1C reduction of 1.1% compared with 0.1% for placebo. The group taking the study drug lost 3.7 kg compared with 1.1 kg for placebo.

From an average baseline A1C of 8%, the share of people reaching the target A1C of 7% by week 26 was greater with oral semaglutide than with placebo: 64% versus 21%, respectively. A target of 7% is recommended by the American Diabetes Association and other major diabetes professional organizations, as well as the Joslin Diabetes Center.

According to the statement² from Novo Nordisk, PIONEER 5 involved 2 statistical approaches:

• A primary approach required by regulatory guidance that evaluates the drug’s effect, regardless of discontinuation of treatment or use of rescue medication. During the trial, 15% discontinued treatment due to adverse events, primarily nausea, compared with 6% who discontinued while taking placebo.
• A secondary approach described the effect of the drug while on treatment, without the use of rescue medication.

The population in PIONEER 5 had T2D and moderate renal impairment inadequately controlled with metformin, sulfonylurea alone or in combination with metformin, or basal insulin alone or in combination with metformin.

“The results from PIONEER 5 showed that oral semaglutide is efficacious and has a solid safety profile in people with type 2 diabetes and moderate renal impairment, thereby further expanding the solid clinical profile of oral semaglutide,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer, Novo Nordisk.

“Renal impairment is a serious diabetes complication and people with this condition have limited oral anti-diabetic treatment options,” he said. “If approved, oral semaglutide represents an efficacious new solution.”

References:

1. Caffrey M. FDA approves Semaglutide, Novo Nordisk’s once-weekly GLP-1 for type 2 diabetes. The American Journal of Managed Care^® website. ajmc.com/newsroom/fda-approves-semaglutide-novo-nordisks-onceweek- ly-glp1-for-type-2-diabetes. Published December 5, 2017. Accessed August 20, 2018.
2. Oral semaglutide provides superior HbA1C and weight reductions versus placebo in people with type 2 diabetes and renal impairment in the PIONEER 5 trial [press release]. Bagsvaerd, Denmark: Novo Nordisk; August 20, 2018. http://hugin.info/2013/R/2211959/862238.pdf?rel=0" . Accessed August 20, 2018.

Stricter Blood Pressure Guidelines Could Prevent Cardiovascular Events, but Debate Continues

A year ago, the American College of Cardiology (ACC), and the American Heart Association (AHA) updated new blood pressure guidelines¹ that lowered the threshold, from 140/90 mm Hg to 130/80 mm Hg, at which some patients should be treated for hypertension.

A new study, published in the AHA journal, Circulation, found that guideline change could translate into 3 million fewer cardiovascular disease events over 10 years, compared with earlier guidelines.² “Treating high blood pressure is a major public health opportunity to protect health and quality of life for tens of millions of Americans,” said lead author Adam Bress, PharmD, MS, assistant professor of Population Health Sciences at University of Utah Health, in a statement.³ “Achieving these lower goals will be challenging.”

But along with commentary, Bress’ study is just one among several that have come recently that show, despite a landmark National Institutes of Health (NIH) study in 2015 that seemed like a mandate for lower blood pressure targets, not everyone is on board. The new study additionally says that for the highest-risk cardiovascular patients, the new guidelines could result in an increase of treatment-related serious adverse events, which suggests the need for personalized care.

One challenge is the Western diet, which is cited as the cause of rising levels of obesity and diabetes around the world. The assumption that blood pressure must rise with age may not be true, and it may be more closely connected to what we eat.

In a study recently published4 in JAMA Cardiology compared the blood pressure of 2 remote South American tribes, one which had no exposure to Western dietary patterns and the other which had some exposure to processed foods with higher levels of salt. Despite similar genetic backgrounds, the tribe that consumed saltier foods had higher blood pressure. Many believe the real key to treating heart disease and diabetes is getting serious about dietary and nutrition policy.

Bress and his team calculated fewer events in middle-aged adults based on the 2017 blood pressure goals when compared with guidelines in the seventh report of the Joint National Committee, known as JNC7, as with the eighth report of the Joint National Committee (JNC8), which put the cutoff for hypertension at 140/90 mm Hg for patients younger than 60 and 150/90 mm Hg for those aged 60 or older.

Franz H. Messerli, MD, and Sripal Bangalore, MD, MHA, writing in the Journal of the American College of Cardiology recently explained how physicians are justifiably confused. They offer a case study of a 63-year-old female patient with blood pressure readings that average 148/86 mm Hg. Guidelines between ACC/AHA, which cover 25,000 cardiologists, and those of the European Society of Hypertension and European Society of Cardiology, which cover 75,000 physicians, are not in alignment.⁵

ACC/AHA guidelines say her blood pressure should be 130/80 mm Hg. The European guidelines say her blood pressure should be 140/90 mm Hg. However, guidelines for the American College of Physicians and the American Association of Family Physicians say she is just fine at 150/90 mm Hg. The guidelines also do not align on how many medications to use when starting treatment.

Ironically, all 3 guidelines are based on the same study, called SPRINT (Systolic Blood Pressure Intervention Trial). This was a large trial⁶ by the NIH that stopped early because it became clear that treating patients to a lower blood pressure target was resulting in fewer fatal cardiovascular events.

Despite this, the American College of Physicians and the American Association of Family Physicians guidelines insist that treating blood pressure to a target of 130/80 mm Hg across a population of older adults will result in “low-value care.”

Messerli and Bangalore see more frustration ahead. “The above hypertension guideline fiasco eloquently illustrates the potential shortcomings of dogmatic clinical directives and, if anything, is prone to increase the rift between those who preach, those who teach, and those who treat,” they wrote.

“Unless we make a concerted effort to do so, as the number of guidelines is increasing more rapidly than does iron-clad evidence, we are prone to see more and more schism among recommendations, confusion among physicians, and anxiety among patients,” the authors concluded.

References:

1. Caffrey M. High blood pressure starts at 130/80, new guidelines say. The American Journal of Managed Care^® website. ajmc.com/conferences/aha-2017/80-new-guidelines-say. Published November 13, 2017. Accessed November 19, 2018.
2. Bress AP, Colantonio LD, Cooper RS, et al. Potential cardiovascular disease events prevented with adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline [published online November 19, 2018]. Circulation. doi: 10.1161/CIRCULATIONAHA.118.035640.
3. New blood pressure guideline could prevent 3 million cardiovascular events over 10 years [press release.] Salt Lake City, UT: University of Utah Health; November 19, 2018. eurekalert.org/pub_releases/2018-11/uouh- nbp111618.php. Accessed November 19, 2018.
4. Reinberg S. Must blood pressure rise with age? remote tribes hold clues. HealthDay website. consumer. healthday.com/circulatory-system-information-7/blood-pressure-news-70/must-blood-pressure-rise-wth-age-remote-tribes-hold-clues-739669.html. Published November 14, 2018. Accessed November 19, 2018.
5. Messerli FH, Bangalore S. The blood pressure landscape: schism among guidelines, confusion among physicians, and anxiety among patients. J Am Coll Cardiol. 2018;72(11):1313-1316. doi: 10.1016/j.jacc.2018.07.026.
6. Caffrey M. 5 things to know about the SPRINT study. The American Journal of Managed Care^® website. ajmc.com/newsroom/5-things-to-know-about-the-sprint-study. Published November 13, 2015. Accessed November 19, 2018.

Amgen Announces 60% Reduction in List Price of PCSK9 Inhibitor Evolocumab

In alignment with the American Heart Association’s Value in Healthcare Initiative, Amgen has announced that the price of its proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab (Repatha), will be reduced by approximately 60%, from an annual price of about $14,100 down to $5850.

Evolocumab was approved in 20151 for use in addition to diet and maximally tolerated stain therapy in adult patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of low-density lipoprotein cholesterol. Its staunch competitor, Sanofi-Regeneron’s alirocumab (Praluent), was approved just a month prior to treat patients with familial hypercholesterolemia, as well as high-risk patients with demonstrated heart disease whose cholesterol has not been controlled with maximally tolerated statins.

However, the launch price of these drugs was a point of contention and debate for a while. Alirocumab also had an annual price tag of over $14,000.

An early report from the Institute for Clinical and Economic Review (ICER) proposed that the PCSK9 inhibitors should cost 85% less² than what they were listed at. “Our draft report suggests that $2177 is the price that should serve as an alarm bell—if the cost is more than $2177 a year, drug companies, doctors, insurers, and other parties may need to work together to determine ways to limit the use of these drugs, find savings in other parts of the health care system, or adopt other measures to help make these drugs more affordable,” Steven D. Pearson, MD, MSc, the founder and president of ICER, had said about their analysis.

Earlier this year, Sanofi and Regeneron announced a deal³ that the companies struck with pharmacy benefit manager (PBM) Express Scripts, under which alirocumab was included in the PBM’s National Preferred Formulary and would cost much less than its $14,000 annual price tag for patients who purchase the drug through Express Scripts.

In a press release,⁴ Amgen’s chairman and CEO, Robert A. Bradway pointed out that patient out-of-pocket cost burden is a big barrier to access for the significant number of patients who suffer from cardiovascular disease, including 75% of Medicare patients who are prescribed a PCSK9 inhibitor but never fill the prescription because of the price burden. “We want to make sure that every patient who needs Repatha gets Repatha,” Bradway said.

Amgen has been offering payers significant rebates on Repatha in exchange for improved patient access through tactics such as healthcare utilization management criteria. Additionally, agreements with payers representing greater than 65% of Repatha’s commercial revenue are currently in place, according to the release.

“Higher rebates don’t typically result in lower out-of-pocket costs for patients, especially for Medicare patients,” said Murdo Gordon, executive vice president of Global Commercial Operations at Amgen. “We are confident today’s action will address this challenge.”

Evolocumab’s original list price of $14,000 is expected to be phased out by late 2020.

References:

1. Caffrey MK. Repatha, Amgen’s PCSK9 competitor, gains FDA approval. The American Journal of Managed Care^® website. ajmc.com/newsroom/evolocumab-amgens-pcsk9-competitor-gains-fda-approval. Published August 27, 2015. Accessed October 24, 2018.
2. Joszt L. PCSK9 inhibitors should cost 85% less, ICER reports. The American Journal of Managed Care^® website. ajmc.com/newsroom/pcsk9-inhibitors-should-cost-85-less-icer-reports. Published September 10, 2015. Accessed October 24, 2018.
3. Caffrey M. Sanofi, Regeneron to cut Praluent prices under exclusive Express Scripts deal that ends prior approval delays. The American Journal of Managed Care^® website. ajmc.com/newsroom/sanofi-regeneron-to-cut-pra- luent-prices-under-exclusive-express-scripts-deal-that-ends-prior-approval-delays. Published May 1, 2018. Accessed October 24, 2018.
4. Amgen makes Repatha (evolucumab) available in the US at a 60% reduced list price [press release]. Thousand Oaks, CA: Amgen; October 24, 2018. prnewswire.com/news-releases/amgen-makes-repatha-evolocumab-avail- able-in-the-us-at-a-60-percent-reduced-list-price-300737367.html. Accessed October 24, 2018.

Gallup-Sharecare Report Shows How Diabetes Ranks Grew Across the United States

Rates of obesity and diabetes continue to rise at alarming rates in the United States, and a decade’s worth of data show how another 1.7 million Americans were diagnosed with diabetes because the disease is becoming more common, according to a new report.¹

The Gallup-Sharecare 2017 State and Community Rankings for the Prevalence of Diabetes, gleaned from the Gallup-Sharecare Well-Being Index, found that the overall diabetes rate increased from 10.8% nationwide in 2008 to 2009 to 11.5% in 2016 to 2017.

But distribution patterns of the disease, as well as obesity, which helps drive it, are hardly equal. According to Dan Witters, research director of the Gallup- Sharecare Well-Being Index, states and communities that had high rates of diabetes a decade ago generally still do.

In general, these states have higher rates of poverty and smoking; dietary patterns and sedentary lifestyles also contribute to rates of diabetes that top 13% and obesity rates that exceed 30% (in 2016-2017) for the 10 states with the unhealthiest profiles: Indiana, Oklahoma, Tennessee, Alabama, Arkansas, Louisiana, Kentucky, Mississippi, South Carolina, and West Virginia.

The index also breaks down diabetes and obesity rates by metropolitan statistical area, and the 10 communities with the highest rates of diabetes and obesity are: Spartanburg, South Carolina; Lakeland-Winter Haven, Florida; Visalia-Porterville, California; McAllen-Edinburg-Mission, Texas; Youngstown- Warren-Boardman, Ohio and Pennsylvania; Beaumont-Port Arthur, Texas; Shreveport-Bossier City, Louisiana; Ocala, Florida; Kingsport-Bristol, Tennessee and Virginia; and Fort Smith, Arkansas and Oklahoma.

Both the report and years of CDC data show the strong relationship between high obesity rates and subsequent high rates of diabetes. “About 54% of middle aged Americans who are obese and have not yet developed diabetes will do so in their lifetime,” the report states. Indeed, the report found that over the past decade, obesity rates climbed in 34 states, and 15 of these states also had a corresponding rise in diabetes. “States with a rising obesity rate are about 2.3 times more likely to also be experiencing rising diabetes prevalence than are states without a rising obesity rate,” the report states.

Both Witters and Sheila Holcomb, RD, LD, CDE, vice president for Sharecare, discussed the implications of these trends for the nation’s healthcare system as the population ages and more Americans move into Medicare. “It was eye-popping for us,” Witters said in an interview with The American Journal of Managed Care^®. “It was more grim than what I was bracing for.”

“The basic rule is for every 3% increase in obesity, there is a 1% increase in diabetes. You’ll find that in the states, too. And no states have seen obesity go down.” This finding is consistent with data released by the CDC that show the number of Americans with diabetes rising past 30 million in 2017, with all but 1.25 million having type 2 diabetes.²

Holcomb said turning the tide on diabetes, as well as obesity, is going to take collaboration at the community level, from getting local leaders to provide more green spaces to getting stores to put produce at the front of the store to getting restaurants to put healthier items on the menu. Schools and workplaces will need to participate by putting healthier items in cafeterias and encouraging people to exercise. Employers will need to pay for gym memberships, she said.

When asked about the resistance former First Lady Michelle Obama encoun- tered when she promoted healthy eating, including healthier school lunches, Holcomb acknowledged that change will come slowly. “It starts in the home,” she said. “Children do whatever they are being exposed to in the home, and that’s the habit they develop for the rest of their lives.”

Witters said changing the culture of American food and exercise patterns will be a long-term struggle. He likened it to the public health effort to combat smoking, which began with the 1964 report to the Surgeon General and continues to this day. In the 1950s, at least half of American adults smoked; today, less than 20% do.

“You don’t turn the Titanic on a dime to get those cultural shifts,” he said. “It takes a generation.”

The good news is some states are passing sugar and soda taxes. “We’re recognizing that more of the cheap, bad-for-you junk food that’s high in processed sugar is turning around and costing our society huge amounts of money down the road,” Witters said.

The report profiles a pair of local health systems—Parkview Health in Fort Wayne, Indiana, and Our Lady of Lourdes Memorial Hospital in Binghamton, New York—that adapted their delivery systems for better diabetes care. Our Lady of Lourdes, in particular, has developed systems to avoid severe hypoglycemia.

Witters and Holcomb see the alarm about diabetes and obesity finally moving out of the healthcare policy and human resources domains, and reaching the level of broader public awareness.

“It has to be local community leaders and healthcare professionals developing these changes,” Holcomb said. “It’s not going to happen overnight.”

Reference:

1. Zero US states lower obesity and diabetes rates in 10-year period [press release]. Atlanta, GA: Sharecare; November 13, 2018. globenewswire.com/news-release/2018/11/13/1650093/0/en/Sharecare-and-Gallup-announce-2017-state-and-community-rankings-for-diabetes-prevalence.html. Accessed November 13, 2018.
2. Diabetes in the US. CDC website. www.cdc.gov/diabetestv/diabetes-in-the-us.html. Published September 19, 2017. Accessed November 13, 2018.

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