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Friday, July 12, 2019

Calorie Restriction: A Win for Heart Health

Calorie restriction helped improve all factors of metabolic syndrome in people without obesity, according to the phase II CALERIE trial.
Adults who restricted their calories by 12% — about 300 fewer calories a day — saw significant improvement in metabolic syndrome score compared with adults on a control diet after 12 months, and this improvement was maintained through 24 months, William Kraus, MD, of Duke University School of Medicine in Durham, North Carolina, and colleagues wrote in The Lancet Diabetes & Endocrinology.
Compared with the control dieters, calorie restrictors saw significant improvements in multiple cardiovascular risk factors from baseline through two years of the diet:
  • Systolic BP: +2.15 mm Hg (control) vs -2.20 mm Hg (calorie restriction)
  • Diastolic BP: +1.55 mm Hg vs -3.40 mm Hg
  • LDL-cholesterol: +0.03 mmol/L vs -0.23 mmol/L
  • Total cholesterol to HDL-cholesterol ratio: -0.047 vs -0.532
  • Triglycerides: -0.03 mmol/L vs -0.27 mmol/L
Calling the trial “groundbreaking” in an accompanying commentary, Frank Hu, MD, PhD, of Harvard TH Chan School of Public Health in Boston, praised the study for being the “first long-term calorie restriction intervention in non-obese young and middle-aged participants with a large sample size.”
Hu also pointed out that the high retention and compliance rate was a particular strength of the trial, which was “higher than a typical weight loss trial.”
Regardless, the hurdle to this type of intervention is adherence to a calorie-restricted diet long-term in the general population. This was represented by the 18% dropout rate in the calorie-restricted group versus only a 5% dropout rate in those on the control diet.
The benefits of a calorie-restricted diet likely span beyond cardiovascular health, Hu noted, highlighting how this diet strategy is also being studied for slowing the aging process and extending lifespan. Despite these benefits, Hu seemed less then convinced that this diet strategy could actually put a dent in the global obesity epidemic.
“We are living in an increasingly obesogenic environment with an abundance of energy-dense, nutrient-poor foods, which are cheap, readily available, accessible, and heavily marketed,” he wrote, adding that “[b]ecause individual food choices are shaped by the food environment, the long-term sustainability of calorie restriction and its benefits on body weight can be easily undermined.”
Kraus and colleagues also noted some other significant benefits after two years of a calorie-restricted diet, including an improvement in fasting insulin (-1.71 μIU/mL), fasting glucose (-0.05 mg/dL), C-reactive protein (-0.068 nmol/L), and insulin sensitivity (+0.099).
Although not surprised by the many health benefits of a calorie-restricted diet, Kraus told MedPage Today his group was “surprised at the magnitude of the effect in already healthy, relatively young, normal weight individuals. And these effects were above and beyond those due to the weight loss alone.”
More than advocating solely for calorie restriction, Kraus pointed out how “maintaining a healthy weight and getting adequate amounts of physical activity are important health goals,” which should be advocated to patients. However, he also added that it’s “entirely possible that some degree of caloric restriction should be included with these other health behaviors due to its beneficial effects on health parameters.”
The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial included 143 adults on the calorie-restricted diet and 75 adults on an ad libitum control diet with a baseline BMI from 22 to 28, the majority of whom were women. Those on the diet were instructed to restrict their calories by 25%, but few achieved this level of restriction.
During the initial 6 months on the diet, the group averaged a 19.5% decrease in energy intake — accounting for about 480 kcal less per day — which later dropped to an average of 9.1% fewer calories after six months. During the two-year study period, adults on the diet intervention averaged an 11.9% reduction in energy intake per day, or 216 fewer calories a day. Those in the control diet saw a slight, but non-significant 0.8% decrease in mean calorie intake.
After two years, those who restricted their calories saw a 16.5 lb (7.5 kg) drop in body weight and a 2.6 point drop in BMI. The majority of body weight lost was also fat mass — 11.7 lb (5.3 kg) of total weight lost — with only a 4.9 lb (2.2 kg) drop in fat-free mass. They saw a 4.6% reduction in body fat, as well. On the other hand, the control dieters experienced a small 0.2 lb (0.1 kg) increase in body weight after two years.
In a sensitivity analysis controlled for reduction in body weight, Kraus’ group still determined a “substantial residual and significant dose–response effects of calorie restriction on cardiometabolic risk factors,” they reported.
Last Updated July 12, 2019
The study was funded by the National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Kraus and co-authors reported no disclosures.
Hu reported grants from the National Institutes of Health and has received research support from the California Walnut Commission and honoraria for lectures from Metagenics and Standard Process and honoraria from Diet Quality Photo Navigation.

Health companies start reporting next week: 3 things to keep in mind

Health companies will begin reporting second-quarter earnings next week, starting with two Dow components, Johnson & Johnson and UnitedHealth Group Inc.
It has been a tumultuous few months for managed-care companies, pharmaceutical companies and biotechs. Fears around “Medicare for all” weighed on earnings last quarter. Shares of UnitedHealth UNH, +1.50% facing investor anxiety about the implementation a single-payer system, dropped sharply in April even after the company beat Wall Street expectations and boosted full-year guidance. Shares of other insurers and managed-care companies also fell at the time, and biopharma stocks followed suit.
Some of those fears have since dissipated and health stocks have mostly recovered to their pre-April levels. But there’s still some unease about where the health regulatory landscape is headed, and pharmaceutical companies are still facing questions about their long-term growth potential.
Here are three big things on investors’ minds as earnings season kicks off this time around.
Potential changes in health policy
Although it seems that the worst is over for health stocks, the fate of the Affordable Care Act remains uncertain, with 20 state attorneys challenging the law’s constitutionality without its penalty on patients without coverage.
Change could also be coming for drug pricing. The Trump administration has vowed it will drive down drug costs, but how and when is still up in the air. The administration has made several proposals — requiring drugmakers to disclose drug prices in television ads, overhauling the current rebates system and mulling an executive order allowing the U.S. to buy drugs based on the lowest price paid by other countries — but investors aren’t sure which, if any, of those will stick. The administration said on Thursday it would be withdrawing its plan to overhaul the rebates that drugmakers give to middlemen in Medicare, and a federal judge on Monday blocked the plan to require pharmaceutical companies to disclose drug prices in TV ads.
“In the near term… we expect the focus on drug pricing reform (congressional action and/or potential presidential executive orders) will likely dictate sentiment and complicate setups into the print themselves. As such, we expect the sector will be volatile over the next couple of weeks,” UBS analyst Carter Gould wrote in a Thursday note on second-quarter biotech earnings to clients.

Patent expirations and generic competition
Many big biopharma companies rely on just one or two drugs for a big chunk of their revenue. Now they’re facing the twin demons of patent expiration and generic competition. This was a big theme last earnings season and is expected to loom large over second-quarter earnings as well.
A prime example: AbbVie Inc.’s ABBV, -0.57% top-selling drug Humira, which brought in 61% of the company’s revenue in 2018, is facing increasing competition in Europe. The drugmaker warned investors that 2019 sales would drop after competitors like Mylan NV MYL, +0.92%  and Amgen Inc.AMGN, -1.60%   began selling lower-cost biosimilars of the drug in Europe in October.
Sales of AbbVie’s Humira fell 5.6% last quarter, but management assured investors that the company’s pipeline would more than plug up any holes that biosimilar competition to Humira might leave. AbbVie has said the competition will likely reduce overall Humira sales by $2 billion this year.
M&A wave
Investors did not expect that AbbVie would expand its portfolio by acquiring troubled pharmaceutical giant Allergan Plc AGN, -0.12% The deal, announced in late June and worth about $63 billion, adds several big-name cosmetic treatments, like anti-wrinkle injectable Botox and dermal filler Juvéderm, to the AbbVie line-up.
The acquisition came shortly after Pfizer Inc. PFE, -1.26%   agreed to buy cancer-therapy biotech Array BioPharma Inc. ARRY, -0.06%  for $10.64 billion in cash. Earlier that month, Merck & Co. Inc. MRK, -1.72%   bought Tilos Therapeutics Inc.for $773 million, and in May, Merck agreed to acquire Peloton Therapeutics Inc.for around $1.1 billion. In January, Bristol-Myers Squibb Co. BMY, -0.79%   kicked off the new year by announcing it would acquire Celgene Corp. CELG, -0.39%  for an estimated $74 billion.
This wave of megamergers comes as large biopharmaceutical companies look for ways to generate growth. And investors should expect more of these; last month, Moody’s said M&A activity is set to rise and named Amgen Inc. AMGN, -1.60%Biogen Inc. BIIB, +0.64% Gilead Sciences Inc. GILD, +0.38% and Novo Nordisk A/S NVO, -2.84%  as likely acquirers.

J&J trial: Illicit drugs called among ‘primary drivers’ of Okla. opioid crisis

An expert witness on illicit drug trafficking testified Thursday that he believes illegal drugs smuggled in from Mexico and China and diverted prescription drugs are among the “primary drivers” of the opioid crisis in Oklahoma and the United States.
Testifying in defense of Johnson & Johnson, University of Miami Professor Bruce Bagleysaid counterfeit opioids and other drugs laced with fentanyl have increasingly been smuggled into the United States in recent years and that the purity of the drugs and addition of fentanyl has made them more deadly than illegal drugs Americans normally saw in the past.
Many of the counterfeit opioids entering the United States appear indistinguishable from the prescription drugs they are manufactured to look like, Bagley said.
Thursday was day 31 of a trial in which the state of Oklahoma has accused Johnson & Johnson and its subsidiaries of contributing to the state’s opioid epidemic through false and deceptive marketing that understated the addiction and overdose risks of opioids while overstating their therapeutic benefits.

Appeals court to quickly consider Trump family planning abortion ban rule

A federal appeals court says it intends to quickly consider whether the Trump administration can impose new abortion-related restrictions on federally funded family planning clinics.
The 9th U.S. Circuit Court of Appeals on Thursday issued an order in lawsuits brought by more than 20 states and healthcare organizations challenging the new rules. The rules include a ban on taxpayer-funded clinics making abortion referrals.
The appeals court also clarified that the government has the green light to impose the rules as the cases move forward. Some of the plaintiffs had believed an earlier decision from the court blocked the rules.

Janssen files U.S. application for subcutaneous Darzalex

Genmab A/S (OTCPK:GNMSFannounces that licensee Janssen Biotech, a unit of Johnson & Johnson (JNJ -5.2%), has filed a marketing application with the FDA seeking approval for a subcutaneously administered formulation of multiple myeloma med Darzalex (daratumumab).
The FDA first OK’d the intravenous formulation in November 2015.
JNJ is down on reports that the U.S. Department of Justice is pursuing a criminal probe related to its communications to the public about its talcum powder products.
Related ticker: Halozyme (HALO -0.9%) (ENHANZE drug delivery technology enables subcutaneous administration of biologics. Janssen in-licensed it in December 2014).

J&J hit on criminal probe into baby powder asbestos claims

Johnson & Johnson (JNJ -4.6%) is down on below-average volume in apparent response to the news that the U.S. Department of Justice is pursuing a criminal investigation against the company related to its alleged misleading of the public about the possible cancer risks of its talcum powder products.
The company is already mired in thousands of lawsuits from consumers who attribute their cancers to said products.
The company has repeatedly denied any wrongdoing.
Update: A Washington grand jury is examining company documents related to what it knew about the potential cancer risks. Company scientists allegedly wrote memos some years ago warning of the risks.

Biosimilars Struggle to Gain Market Share in the U.S.

Over the past several years, the U.S. Food and Drug Administration has approved a number of biosimilar medications, therapies that have similar properties to a branded drug, but are different in composition, which differentiates them from generic drugs.
The approval of biosimilar treatments has been supported at the highest levels as a means to increase competition in the market and help regulate some of the high costs of prescription drugs. However, despite the numerous approvals of biosimilars, they have not yet gained a significant stake in the marketplace. A recent analysis of the biosimilar landscape in the United States published in Forbes points to several reasons, including the thickets of patent protection some companies, such as AbbVie, have established to protect cash cow drugs like Humira, as well as reticence from some doctors in prescribing those that are available.
In May, the FDA provided its final guidance on the pathway for “interchangeable” biosimilar drugs, which allows for their substitution without the involvement of the prescriber. At the time the guidance was released, the FDA said the rules will provide clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act.” Still, when the guidance was established, there had been no approval of interchangeable biosimilars in the U.S. That could change. For the past two years, Boehringer Ingelheim has been conducting interchangeability studies for a biosimilar to Humira.

Another barrier to increased U.S. use of biosimilars, which are more widely used in Europe, is concern over insurance payments. In its analysis, Forbes said that 40% of payers in the U.S. have no policies in place for conversion to biosimilars, hampered, in part, due to the current rebate system in place. As an example, the analysis in Forbes pointed to approved biosimilars of Janssen’s Remicade. Despite the availability of biosimilars to the Crohn’s disease drug, insurers wildly preferred covering the branded medication.
While it’s been a rocky road for biosimilars in the U.S., there is a fervent belief among some healthcare analysts and activists that increasing the use of these treatments will lead to vast savings. On Thursday, the Pacific Research Institute released a report that shows Americans could pocket more than $71 billion in savings if the use of biosimilars was expanded. But, much like Joshua Cohen who wrote the Forbes analysis, Wayne Winegarden, director of PRI’s Center for Medical Economics and Innovation and author of that group’s analysis, said biosimilars have a small share of the marketplace in the U.S. Only nine biologic drug classes have approved biosimilars, Winegarden said, but, despite this, those biosimilars are currently generating $253.8 million in annual savings. More savings could be generated if those numbers were expanded, he added.  Much like the Forbes analysis, Winegarden noted numerous barriers in place, including the “buy-and-bill” method. This, Winegarden said, is when providers purchase medicines and then bill the payers. Providers often lose money when prescribing biosimilars over the originator biologic because reimbursements are based on the sales price of the medication plus a percentage markup, he said.
“Biosimilars are innovative medications that can treat patients at lower costs. Our research shows that as their market share increases, biosimilars can lead to billions in savings for patients, health providers, and taxpayers – while also helping to treat some very serious illnesses,” Winegarden said in a statement.