A new analysis of blood biomarkers before and after a single session of high-frequency deep transcranial magnetic stimulation (dTMS) in obese individuals offers clues as to how the procedure may help reduce food cravings and thereby lower weight.
As reported byMedscape Medical News, the researchers previously presented a pilot study that showed repeated high-frequency dTMS was associated with an average weight loss of 4.5 kg and reduced food cravings by 34% after 5 weeks compared with a sham procedure in 16 obese patients. They continued to follow the participants and say the effects were maintained for between 6 and 12 months.
The latest results, presented May 21 at the 20th European Congress of Endocrinology (ECE), suggest that dTMS affects metabolic pathways by modulation of sympathetic activity and the hypothalamic-pituitary-adrenal axis.
“For the first time this study is able to suggest how dTMS could alter food cravings in obese subjects,” said Livio Luzi, MD, PhD, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato and University of Milan, Italy, in an ECE press release.
“Given the distressing effects of obesity in patients and socioeconomic burden, it is increasingly urgent to identify new strategies to counteract the current obesity trends. dTMS could present a much safer and cheaper alternative to treat obesity compared with drugs or surgery,” he added.
Comparison of High-Frequency, Low-Frequency, and Sham Procedures
Previous studies have shown that dTMS affects the mesolimbic and mesostriatal pathways in the brain through cortical excitability. Consequently, it has been used in neuropsychiatric disorders linked to abnormal cortical excitability and dopaminergic activity, such as addiction, in particular smoking, as well as resistant epilepsy and major depression.
In the current study, Luzi and colleagues recruited 40 patients (29 women) who were obese (average BMI, 36.3 kg/m2) to examine the effect of a single 30-minute dTMS session — high-frequency (18 Hz), low-frequency (1 Hz), or sham stimulation — targeted at the prefrontal cortex and insula bilaterally. They assessed metabolic and neuroendocrine parameters in the blood before and after stimulation.
Following high-frequency dTMS, patients had a significant increase in norepinephrine (noradrenaline) levels, from 5.6 ng/mL to 6.5 ng/mL, or a 18.0% increase (P = .01; P = .05 vs low-frequency dTMS).
Moreover, patients experienced a significant rise in beta-endorphin levels, from 0.338 ng/mL to 0.372 ng/mL, or a 13.9% increase (P = .017; P = .010 vs sham; P = .011 vs low-frequency dTMS).
Patients given high-frequency dTMS also had a 7.0% increase in blood glucose levels (P = .002) and 16.3% decrease in leptin levels (P = .002).
These changes were accompanied by decreases in pituitary hormones, with a 20.7% decrease in thyroid stimulating hormone (P = .001) and a 16.3% decrease in prolactin levels (P < .0001).
In the low-frequency dTMS group, salivary cortisol levels decreased after just one session by 29.4% (P = .015).
The team also found that some blood markers varied by gender, “suggesting male/female differences in how vulnerable patients are to food cravings and their ability to lose weight,” noted Luzi.
A Few Reasons Why
Speaking to Medscape Medical News, Luzi said it “makes sense” that beta-endorphin release was altered by dTMS, as it “has been demonstrated in all other forms of addiction, so it’s a common mechanism that is involved in any addictive disorder, like food addiction.” This, he said, is important “because the beta-endorphin release means the reward pathway is activated and can be modulated directly in vivo in humans.”
Currently dTMS is only approved, however, for research in obese individuals with a BMI of 30 to 54 kg/m2.
Luzi nevertheless believes that because “the procedure is safe, repeatable, and once you have the machine, is also relatively inexpensive, in my opinion it could be used even earlier, when the person is only overweight and not yet obese, to prevent obesity.”
“But that’s another story, that’s another study, and it’s not our present indication for which we are approved.”
Turning to possible explanations for why dTMS has such a long-lasting effect on food cravings and weight, Luzi said it could affect neuroplasticity, thus modifying neuronal connectivity, and may also have an effect on the gut microbiota.
“Obese people have a completely different intestinal environment. What we found is that…5 weeks of treatment with dTMS nearly normalized the gut microbiota,” he noted.
“But there might be other explanations that we, at present, do not know. It’s still a work in progress.”
The authors have reported no relevant financial relationships.
European Congress of Endocrinology 2018. May 21, 2018; Barcelona, Spain. Abstract OC6.2
It’s official: In the United States, the incidence of lung cancer in young women has now surpassed that of their male counterparts, a collaborative study between the American Cancer Society (ACS) and the National Cancer Institute (NCI) shows.
A report of the study was published online May 22 in the New England Journal of Medicine.
This study “confirms that some of the trends we have been seeing in the oncology clinic over the last few years are true. The research shows that yes, lung cancer is affecting more and more women of younger and younger ages,” said Lecia V. Sequist, MD, MPH, associate professor of medicine at Harvard Medical School and attending physician at Massachusetts General Hospital in Boston. She was not involved in the study and was approached for comment.
The study analyzed data from the North American Association of Central Cancer Registries, which covers 96% of the US population. The analysis showed that in the 20-year period between 1995 and 2014, the overall incidence of lung cancer decreased in both men and women. However, in women of white and Hispanic origin who were born in 1965 or later, the analysis shows that the female-to-male incidence rate ratios exceeded 1.0 for the first time.
Lung cancer mortality rates in young white and Hispanic women approached or equaled those of men but didn’t cross over, say Ahmedin Jemal, PhD, from the American Cancer Society, Atlanta, Georgia, and colleagues.
In white women 40 to 44 years of age, the incidence rate ratio increased from 0.88 between 1995 and 1999 to 1.17 between 2010 and 2014. During the same time periods, the female-to-male incidence rate ratio in Hispanic women jumped from 0.79 to 1.22.
Similarly, in white adults age 45 to 49 years, the female-to-male incidence rate ratio increased from 0.81 to 0.83 in the cohort born around 1950, and to 1.13 in the cohort born around 1965. In Hispanic adults, this ratio increased from 0.64 to 0.72 in those born around 1950 to 1.12 in those born in the mid-1960s.
The sex-based crossover in female-to-male incidence ratios is “especially remarkable” in the Hispanic population because “smoking prevalence among its young adults is substantially lower among women than men,” the researchers say.
They point out that the overall number of women who smoke has not exceeded the number of male smokers, and that on average, women smoke fewer cigarettes per day than men. Women are also less likely than men to use tobacco products such as cigars and chewing tobacco, they add.
These sex differences in smoking behaviors do not fully account for the historic reversal in female-to-male incidence rate ratios, Jemal and colleagues say. Nevertheless, this finding has important implications for public health, they add.
“It may foreshadow a higher future burden of overall lung cancer among women than among men as younger cohorts age, which further underscores the need to intensify antitobacco measures to decrease smoking among young women,” the authors write. “Our finding also calls for continued monitoring of sex-specific risks of lung cancer and for etiologic studies, including studies of sex differences in smoking-related susceptibility to lung cancer, to identify reasons for the higher rates of lung cancer among young women.”
Although the age-specific incidence of lung cancer has been declining for the past two decades in both men and women 30 to 54 years of age across all races and ethnic groups, these declines have been steeper in men, the investigators note. Cigarette smoking contributes to about 80% of the 154,000 lung cancer deaths that occur in the United States each year, and cancers of the lung and bronchus remain the country’s top causes of preventable cancer death, they point out.
Commenting on the findings, Sequist agreed that more research is needed to understand the reasons behind the trends that were revealed by the new study.
“More than ever we need better early detection methods that can reach broader populations,” she told Medscape Medical News. “Smoking cessation is not the only tool to prevent lung cancer, since an increasing number of cases are being diagnosed in never-smokers.”
For the study, Jemal and colleagues examined the nationwide population-based incidence of lung cancer and calculated the age-specific incidence of lung cancer per 100,000 person-years, as well as female-to-male incidence rate ratios according to sex, race or ethnic group, and histologic type. They also looked at age group from 30 to 54 years, birth years from 1945 to 1980, and calendar period of diagnosis from 1995 to 2014. Data from the National Health Interview Survey from 1970 to 2016 were used to determine the prevalence of cigarette smoking.
The fact that women have been slower than men to quit smoking may be contributing to the increasing female lung cancer incidence rates, they suggest. More frequent detection of indolent lung tumors in women than in men through screening or diagnostic imaging could also explain the higher rates of lung cancer among women.
Lung cancer may also progress more slowly in women than in men, Jemal and colleagues point out. A recent study of baseline CT screening for lung cancer in North America showed that the prevalence of lung cancer among women was nearly twice as high as that among men of similar age and with similar smoking history, they note.
This study was funded by the American Cancer Society. The authors have disclosed no relevant financial relationships.
More than 200 people in nine states have developed serious, unexplained bleeding linked to synthetic cannabinoids thought to be laced with rat poison, federal health officials with the Centers for Disease Control and Prevention (CDC) said today.
Since the first case was identified in Illinois on March 3, 2018, state health departments have now reported 202 cases of potentially life-threatening vitamin K–dependent antagonist coagulopathy after using synthetic cannabinoids. Five individuals have died. The CDC previously reported 94 cases in five states and two deaths.
In today’s advisory, the CDC says Illinois has reported 164 cases; Maryland, 20 cases; and Florida, Indiana, Kentucky, Missouri, Pennsylvania, Virginia, and Wisconsin, six or fewer cases per state.
More than 95 biological samples from case patients have tested positive for brodifacoum, a highly lethal vitamin K antagonist anticoagulant used in commercial products for killing rodents and other pests.
Synthetic cannabinoids are sold under a variety of names, including K2 and Spice. Adverse effects from the use of synthetic cannabinoids vary and can include neurologic, psychiatric, and other physical signs and symptoms.
Case patients from this multistate outbreak have presented with a variety of signs and symptoms of coagulopathy, including bruising, nosebleeds, excessively heavy menstrual bleeding, hematemesis, hemoptysis, hematuria, flank pain, abdominal pain, and bleeding from the gums or mouth, the CDC reports.
Some patients were asymptomatic or presented with complaints unrelated to bleeding but were found to have “numerical coagulopathy,” which may put the patient at risk for bleeding complications associated with injuries and invasive or surgical procedures. “Patients should be considered high-risk for coagulopathy if they have reported use of or are suspected of using synthetic cannabinoids,” the CDC advises.
They note that case confirmation requires detection of brodifacoum in blood, serum, plasma, or urine, as determined by laboratory testing. “Clinicians and healthcare providers should work with their healthcare facility’s laboratory to determine what options are available to them for brodifacoum testing,” the CDC says.
The agency is currently coordinating national surveillance activities for possible cases of vitamin K–dependent antagonist coagulopathy associated with use of synthetic cannabinoids.
The CDC is also asking healthcare providers to maintain a high index of suspicion for vitamin K–dependent antagonist coagulopathy in patients who present with clinical signs of coagulopathy, bleeding unrelated to an injury, or bleeding without another explanation and who have a possible history of use of synthetic cannabinoids.
These patients should be screened for vitamin K–dependent antagonist coagulopathy through assessment of their coagulation profile. For purposes of reporting cases, an international normalized ratio >2 is being used as a criteria to help identify and classify possible cases, the CDC says. Possible cases should be reported to the local or state health department.
Possible case patients should be asked whether they have donated plasma or blood in the past 3 months. Clinicians treating possible case patients who have recently donated plasma or blood should notify their state health department, which can then notify the US Food and Drug Administration.
The CDC states that proceduralists (trauma/general/orthopedic/oral/ob-gyn/cosmetic surgeons, dentists, interventional cardiologists/radiologists, and nephrologists) should be aware that patients with a history of using synthetic cannabinoids may be experiencing anticoagulation in the absence of clinical signs of coagulopathy. These patients should be screened for vitamin K–dependent antagonist coagulopathy before undergoing their procedure, the CDC advises.
In addition, patients sent home after having undergone surgeries or other procedures that could result in bleeding should be advised not to use synthetic cannabinoids, because the product could be contaminated with an anticoagulant.
Healthcare providers can contact their local poison control center (1-800-222-1222) for questions on diagnostic testing and management of these patients.
Diabetes certainly presents a huge problem. It’s the seventh-highest cause of death in the United States. It’s also one of the fastest-growing diseases: At 29 million, the number of people in the U.S. with diabetes is nearly triple the number 20 years ago. And the problem isn’t limited to the U.S.; diabetes is also the fastest-growing chronic disease in the world.
Many publicly traded companies, both large and small, are developing new drugs and medical devices for diabetes care. The opportunities for investors lie in buying the stocks of the companies most likely to succeed in the growing diabetes market. Here’s what you need to know about how to invest in diabetes stocks.
What is diabetes?
Before investing in diabetes stocks, it’s important to understand exactly what diabetes is: a common disease that occurs when individuals’ blood glucose (“blood sugar”) levels become too high.
Glucose enters the bloodstream from food. Normally, insulin, a hormone produced by the pancreas, helps make sure the glucose moves from the blood to cells, to provide energy for those cells. But when the body doesn’t make enough insulin — or doesn’t use it properly — glucose stays in the blood rather than reaching the cells. If not managed, diabetes can lead to several serious health problems; these include eye problems, dental disease, foot problems, heart disease, kidney disease, nerve damage, and stroke.
The A1C test is the most frequently used method of testing for diabetes. It’s a blood test that measures the amount of hemoglobin — a protein in blood that carries oxygen — with attached glucose. The measurement reflects the patient’s average blood glucose levels over the previous three months. A1C levels are reported as a percentage, with a higher percentage representing higher blood glucose levels. Individuals with diabetes have A1C levels of 6.5% or higher.
How big is the diabetic population?
More than 30 million Americans have diabetes, according to the Centers for Disease Control and Prevention (CDC). Another 84 million have prediabetes — where blood glucose levels are high (between 5.7% and 6.4%) but not high enough to be considered diabetes. Prediabetes is a risk factor for diabetes, and the higher the patient’s A1C level is, the greater the risk.
Types of diabetes
There are three common types of diabetes, along with other less common types of the disease.
Type 1 diabetes
With type 1 diabetes, the body doesn’t make insulin at all. Most frequently this is because the immune system attacks cells in the pancreas that produce insulin. Patients with this type of diabetes must take insulin every day to live. Around 1.25 million Americans have type 1 diabetes, with the disease typically diagnosed in children and young adults.
Type 2 diabetes
The most common form of diabetes is type 2 diabetes. With this type, the body either doesn’t produce enough insulin, or doesn’t use it very well. Type 2 diabetes can be caused by several factors, including lack of physical activity, being overweight, insulin resistance, and genetics. Around 28 million Americans have this form of the disease.
Gestational diabetes
Gestational diabetes occurs in 2% to 10% of pregnant women in the U.S. Changes during pregnancy, such as increased production of hormones and weight gain, cause the body to use insulin less effectively; as a result, the body can’t make enough insulin. Around 50% of women with gestational diabetes go on to develop type 2 diabetes.
Other types of diabetes
Two other less common types of the disease are monogenic diabetes and cystic-fibrosis-related diabetes. “Monogenic” diabetes results from changes in a single gene (the more common forms are “polygenic”); this type accounts for 1% to 4% of all cases of diabetes.
Cystic-fibrosis-related diabetes (CFRD) occurs when the thick, sticky mucus associated with cystic fibrosis (a genetic disease) causes scarring of the pancreas. This scarring results in the pancreas being unable to make enough insulin. More than 30,000 Americans have cystic fibrosis, with 20% of adolescents with the disease also suffering from CFRD and between 40% and 50% of the adults having CFRD.
How is diabetes treated?
Some cases of Type 2 diabetes can be managed through diet and exercise. However, type 1 diabetes and many cases of type 2 diabetes require more involved treatment. There are several components that can be part of managing and treating diabetes.
Glucose monitoring
Monitoring glucose levels is critical for both type 1 and type 2 diabetic patients.
Individuals with type 1 diabetes typically must check their glucose levels four to 10 times per day, including prior to eating, before and after exercise, and before going to sleep. Some type 1 patients must also check their glucose levels during the night. Also, some people with type 1 diabetes use continuous glucose monitors (CGMs), devices with sensors beneath the skin that check blood glucose levels every few minutes.
Type 2 diabetic patients usually must monitor their glucose levels at least twice each day — before breakfast and dinner. Some individuals with type 2 diabetes must check their glucose levels before each meal and at bedtime.
Insulin
All type 1 diabetic patients and many type 2 diabetic patients must take insulin. There are four key types of insulin:
TYPE
HOW FAST THE INSULIN BEGINS TO WORK
PERIOD WHEN THE INSULIN IS MOST EFFECTIVE
HOW LONG THE INSULIN WORKS
Rapid-acting
15 minutes after injection
~1 hour
2-4 hours
Short-acting
30 minutes after injection
2-3 hours
3-6 hours
Intermediate-acting
2-4 hours after injection
4-12 hours
12-18 hours
Long-acting
Up to 4 hours after injection
Lowers glucose levels relatively evenly with minimal peak
Up to 24 hours
Data source: American Diabetes Association.
Insulin can be administered using a variety of devices:
Needle and syringe
Insulin pen (an easy-to-use penlike device for self-injection)
Insulin pump (a small device that delivers regular small doses, and higher doses when needed)
Inhaler
Injection port (a short tube inserted beneath the skin)
Jet injector (a high-pressure insulin spray)
Other medications
Some type 2 diabetic patients also are prescribed non-insulin medications. Common types of diabetes medications include:
TYPE OF DRUG
HOW THE DRUGS WORK
EXAMPLES
Sulfonylureas
Stimulate beta cells in the pancreas to produce more insulin
Diabinese, Glucotrol, Micronase
Biguanides
Decrease the amount of glucose produced by the liver
Metformin
Meglitinides
Stimulate beta cells in the pancreas to produce more insulin
Prandin, Starlix
Thiazolidinediones
Make insulin more effective and decrease the amount of glucose produced by the liver
Avandia, Actos
DPP-4 inhibitors
Prevent the breakdown of GLP-1, a peptide that reduces blood glucose levels
Januvia, Onglyza, Tradjenta
SGLT2 inhibitors
Help the kidneys reabsorb glucose
Invokana, Farxiga, Jardiance
Alpha-glucosidase inhibitors
Prevent the breakdown of starches, thereby reducing glucose levels
Glyset, Precose
Data source: American Diabetes Association.
Factors driving the diabetes market
By 2030, diabetes is projected to affect nearly 55 million Americans and 552 million people worldwide. In the U.S., total annual medical and societal costs related to diabetes are projected to increase by 53% to more than $622 billion. And the global total direct and indirect cost of diabetes is estimated to almost double by 2030 to $2.5 trillion.
Several factors are driving growth in the diabetic patient population and increased spending on diabetes.
1. Aging populations
One key trend that will likely increase the number of cases of diabetes is the growth in senior populations across the world. As people age, they’re less likely to get enough exercise, which can result in added weight — both of which are key factors that can contribute to type 2 diabetes.
2. Lower levels of physical activity in youth
Not just the older part of the population is a cause for concern. Children and adolescents are also getting less physical activity, which has already led to a higher prevalence of type 2 diabetes in youth. Only one in three U.S. children is physically active every day, according to the U.S. Department of Health and Human Services. Children spend more than seven and a half hours a day, on average, in front of a computer, smartphone, TV, or video game screen.
3. Developing nations adopting Western lifestyles
Another driver of greater diabetes prevalence comes from developing countries. As the middle classes expand in these nations, their citizens are more likely to adopt lifestyles associated with the Western world, including unhealthy diets and less exercise.
4. New drugs and devices for managing diabetes
Obviously, the increased numbers of patients diagnosed with diabetes will play a key role in higher costs. Ironically, better treatments for diabetes are also anticipated to contribute by prolonging the lives of patients with diabetes, which increases the costs over the long run of managing their related health problems. In addition, new drugs and devices for managing diabetes are more expensive than older products, driving costs up even more.
Diabetes stocks
Diabetes stocks fall into three broad categories: Drugmakers, medical-device makers, and companies that market medical supplies for diabetes. Below is a list of diabetes stocks with market caps of at least $200 million.
COMPANY
CATEGORY
MARKET CAP
FORWARD P/E
DIVIDEND YIELD
Abbott Laboratories(NYSE: ABT)
Drugs
$109 billion
19.37
1.88%
AstraZeneca(NYSE: AZN)
Drugs
$93 billion
19.70
3.97%
Becton Dickinson and Co.(NYSE: BDX)
Medical supplies
$60 billion
17.74
1.29%
DexCom(NASDAQ: DXCM)
Medical devices
$8 billion
N/A
N/A
Eli Lilly and Co.(NYSE: LLY)
Drugs
$85 billion
14.91
2.77%
Insulet(NASDAQ: PODD)
Medical devices
$5 billion
273.03
N/A
Johnson & Johnson(NYSE: JNJ)
Drugs, medical devices
$325 billion
14.16
2.57%
Lexicon Pharmaceuticals(NASDAQ: LXRX)
Drugs
$1 billion
N/A
N/A
MannKind(NASDAQ: MNKD)
Drugs
$270 million
N/A
N/A
Medtronic(NYSE: MDT)
Medical devices
$117 billion
15.36
2.14%
Merck & Co.(NYSE: MRK)
Drugs
$159 billion
12.99
3.22%
Novo Nordisk(NYSE: NVO)
Drugs
$116 billion
18.29
2.61%
Pfizer(NYSE: PFE)
Drugs
$209 billion
11.62
3.82%
Regeneron Pharmaceuticals(NASDAQ: REGN)
Drugs
$32 billion
13.95
N/A
Sanofi(NYSE: SNY)
Drugs
$95 billion
10.75
4.64%
Senseonics Holdings(NYSEMKT: SENS)
Medical devices
$447 million
N/A
N/A
Tandem Diabetes Care(NASDAQ: TNDM)
Medical devices
$711 million
N/A
N/A
Data source: Yahoo! Finance. P/E = price-to-earnings ratio; N/A = not applicable. Data as of May 25, 2018.
Factors to consider in evaluating diabetes stocks
What should you look for in a diabetes stock? Well, for starters, you’ll want to evaluate the company just as you’d research any potential investment. Key factors to consider include:
1. Diabetes products’ contribution to total revenue
How significant is the diabetes market to the company? A company that makes most of its revenue in other ways won’t benefit as much from the growth in the diabetes market.
Pfizer, for example, co-markets new diabetes drugs Steglatro, Steglujan, and Segluromet with Merck. But those are the only diabetes drugs in Pfizer’s lineup; although they’re expected to become a blockbuster franchise for the two companies, diabetes will still represent only a small portion of Pfizer’s overall revenue.
If you are looking to put money behind the diabetes market specifically, investing in a stock like Pfizer might not be your best bet. Buying a pure-play stock like Senseonics gives you greater exposure to the diabetes market, but it’s also riskier than a diversified company like Pfizer. If this market doesn’t grow as quickly as projected, it would have a much greater negative impact on Senseonics than it would Pfizer.
2. Competitive advantages and risks
Although the diabetes market is huge, it’s still very competitive. Companies that enjoy competitive advantages stand a better chance of long-term success.
However, even successful products face the risk of losing market share to a rival. When brand-name drugs lose patent exclusivity, other companies can launch cheaper generic versions of the drug. With a biologic drug — one made from a living organism or its products — rivals can launch knockoff biosimilars after it loses patent exclusivity.
Of course, a drug doesn’t have to have its patents expire to lose market share. New drugs can come on the scene that are more effective, safer, and/or less costly.
3. Development risks
The drug development process is risky. This process begins with preclinical testing in animals. If that testing goes well, approval must be obtained from regulators to advance to testing in humans.
There are usually three phases of clinical testing of a new drug in humans. Phase 1typically involves only a few patients and focuses on assessing the safety of the drug. Phase 2 includes more patients and evaluates the efficacy of the drug in addition to safety. Phase 3 clinical studies are usually much larger and take more time — often between one and four years. These phase 3 studies focus on efficacy and potential adverse reactions. If drugs are shown to be successful in clinical testing, drugmakers submit for regulatory approval by the U.S. Food and Drug Administration (FDA) and similar agencies in other countries.
Each step in this process holds the potential for failure. For every 10 drug candidates that start in phase 1 clinical studies, on average only one will make it all the way to approval.
The process for winning approval for new medical devices targeting diabetes care also requires several hurdles to be jumped. Companies must first test prototypes of the new medical devices in controlled settings that don’t involve humans. The pathway to approval then depends on the risk that the device presents. Devices that hold significant risks for patients must go through clinical trials and FDA review similar to that for new drugs. There’s no guarantee that a new medical device will be cleared for marketing by the FDA.
So what should investors do about these development risks? Choosing stocks with pipeline candidates in late-stage development is less risky than picking stocks with early-stage drugs. Also, companies with more pipeline candidates have more “shots on goal,” which improves the overall chances of success.
4. Reimbursement risks
Once a drug or medical device wins regulatory approval, there’s another challenge: securing reimbursement. In the U.S., pharmaceutical and medical-device companies must negotiate with health insurers to get their products covered for reimbursement. Drugmakers also have to negotiate with pharmacy benefits managers (PBMs) — third-party administrators of programs that attempt to control prescription drug costs for their customers. In Europe, where universal healthcare plans are paid for by national governments, companies must negotiate pricing on a country-by-country basis.
It’s possible that a new product can get a green light from regulatory agencies but not win favor with payers. Even if a product does secure reimbursement coverage, there’s no guarantee that the desired price will be negotiated. Payers can also put additional obstacles in the way, such as mandating that patients obtain prior authorization before using a new product. All of this is to say that just because a new product is approved, that doesn’t mean you can count on it succeeding commercially.
Top diabetes stocks to consider
So in light of these key factors and risks, what are the best diabetes stocks to consider? I think three especially stand out.
Abbott Labs
Although Abbott Labs doesn’t currently detail how much of its revenue is generated from diabetes-care products, diabetes is becoming an increasingly important growth driver for the company. This new dynamic is primarily the result of FDA approval in September 2017 for Abbott’s new flash glucose monitoring system FreeStyle Libre.
It’s important for many diabetic patients to continuously monitor their blood glucose levels. The drawback to most continuous glucose monitoring (CGM) systems is that they require patients to calibrate the systems by sticking their fingers several times per day to test blood glucose levels.
FreeStyle Libre eliminates the need for those pesky finger sticks, and has a much lower cost than most CGM systems. As you might imagine, those are significant competitive advantages for Abbott. Dexcom recently launched its G6 CGM system that doesn’t require finger sticks, but it’s more expensive than the FreeStyle Libre.
Abbott Labs is highly unlikely to need to raise any cash by issuing more stock: The company reported more than $4 billion in cash, cash equivalents, and marketable securities at the end of the first quarter. Abbott also has one of the most stable dividendsaround, with the company paying a dividend every quarter since 1924 and increasing its dividend payout for 46 consecutive years — making it a longtime member of the elite Dividend Aristocrats.
Lexicon Pharmaceuticals
Lexicon Pharmaceuticals is considerably more risky than Abbott Labs. The company only has one FDA-approved product right now — Xermelo, for carcinoid syndrome diarrhea; the drug launched in the first quarter of 2017. Lexicon awaits regulatory approval for its first diabetes drug, sotagliflozin.
So why consider buying Lexicon stock? Wall Street analysts think it could be one of the fastest-growing diabetes stocks on the market this year. That’s for good reason: If approved, sotagliflozin will be the first combination SGLT1/SGLT2 inhibitor.
SGLT2 (SGLT stands for “sodium-glucose linked transporter,” and the numbers denote the type of cotransporter) is responsible for most of the glucose reabsorption performed by the kidneys. SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and, to a lesser extent than SGLT2, glucose reabsorption in the kidneys. Sotagliflozin could be a huge winner because it’s potentially more effective than SGLT2 inhibitors such as Invokana and Jardiance. As an added bonus, it treats both type 1 and type 2 diabetes.
Novo Nordisk
Novo Nordisk ranks as one of the leaders in the diabetes drug market. The Danish drugmaker’s insulin products Levemir, Tresiba, NovoMix, and NovoRapid are huge moneymakers. But the main reason I like Novo Nordisk is the company’s newer products.
The FDA granted approval to type 2 diabetes drug Ozempic in December. Market research firm EvaluatePharma thinks that Ozempic will be the second-biggest new drug launched in 2018, with more than $2.7 billion in annual sales by 2022. I also like the prospects for Novo’s obesity drug Saxenda, which I see as a great fit with the company’s diabetes lineup.
Don’t forget Novo Nordisk’s dividend, either. Over the last 10 years, investors received an additional 78% in total returns thanks to the drugmaker’s dividend. And with a payout ratioof less than 50%, Novo has plenty of flexibility for dividend hikes in the future.
Unmet opportunities
There are also two unmet opportunities in diabetes that investors should be aware of.
One is in new products that help prevent the disease. Type 2 diabetes is largely preventable through diet and exercise. New superfoods created by gene editing could be game-changers down the road, helping people avoid gaining extra weight that could make them more likely to develop diabetes.
Another is in more convenient ways to monitor glucose levels. Abbott’s FreeStyle Libre is a fantastic innovation on this front, but more advances could be on the way. For example, Alphabet‘s Verily Life Sciences unit is working with Novartis to develop a smart contact lens that senses glucose levels in tears. These contact lenses would change color if diabetic patients’ glucose levels aren’t where they need to be.
Such developments are likely years down the road, at best. But diabetes is such a huge problem that making these technologies become reality should be worth the effort.
Athenahealth has retained a new financial adviser to help analyze Elliott Management’s offer to buy the company, even as it pushed back on claims that most shareholders are gunning for a sale.
In a statement on Thursday, the EHR vendor said it has retained the high-powered investment firm Centerview Partners to assist the board of directors, in addition to Lazard.
The addition of Centerview Capital—which had not been previously disclosed—adds an experienced merger and acquisitions firm to the mix, a sign the board is seriously considering one or more proposals, one person familiar with the situation told FierceHealthcare.
Athenahealth’s statement came in response to a third letter (PDF) from Elliott Management to the board of directors on Thursday in which the firm said a “significant portion” of Athenahealth’s shareholder base is supportive of the exploring a sale, including Elliott Management’s offer.
The letter also noted that the firm is “aware that other parties have expressed interest in participating a sale process.” Meanwhile, analysts have speculated that larger companies, including Cerner, Apple or Amazon, could be interested in acquiring the company.
“Athenahealth’s shareholders have spoken, and it is clear from their words and actions that rejecting the idea of evaluating a sale and instead offering assurances that the Company has a standalone plan for getting back on track will not be accepted,” Jesse Cohn, a partner and senior portfolio manager with Elliott Management wrote in the letter. “The feedback we’ve received suggests that athenahealth would find shareholder patience for such promises exceedingly low.”
That sparked a response from Athenahealth, which said it was conducting a “deliberate analysis of Elliott Management’s proposal” despite the firm’s attempts to “publicly pressure the Board and management team.”
“Although the Company does not comment on the specifics of any conversation with its shareholders, this ongoing engagement has been constructive and has provided an opportunity for shareholders to share their perspectives with management and the Board,” the company said. “Based on our discussions with shareholders, we do not believe the positions set forth in Elliott Management’s letter are representative of the positions of all of our shareholders.”
The EHR vendor has remained relatively quiet following Elliott Management’s highly publicized offering to buy the company for $160 per share earlier this month. The back-and-forth comes less than a week after Athenahealthcare’s top investor, Janus Henderson Group, urged the company to consider a sale in an SEC filing. Analysts told FierceHealthcare that would likely force shareholders to choose sides.
Elliott Management’s public pressure on the company has also created a distinct power struggle between the activist investor and the company, setting up what could be a contentious battle for the company.
“Elliott had control of the narrative and now Athenahealth is pushing back,” said Andrew Freedman, a healthcare analyst with Hedgeye Risk Management.
A cancer treatment that can completely destroy cancer cells without affecting healthy cells could soon be a possibility, thanks to research led by Cardiff University.
The team of researchers has successfully ‘trained’ a respiratory virus to recognise ovarian cancer and completely destroy it without infecting other cells.
The reprogrammed virus could also be used to treat other cancers such as breast, pancreatic, lung and oral.
Dr. Alan Parker from Cardiff University’s School of Medicine said: “Reprogrammed viruses are already being used in gene therapy procedures to treat a range of diseases, demonstrating they can be trained from being life-threatening into potentially lifesaving agents.
“In cancer treatment, up until now, reprogramed viruses have not been able to selectively recognise only the cancer cells and would also infect healthy cells, resulting in unwanted side effects.
“We’ve taken a common, well-studied virus and completely redesigned it so that it can no longer attach to non-cancerous cells but instead seeks out a specific marker protein called αvβ6 integrin, which is unique to certain cancer cells, allowing it to invade them.
“In this case we introduced the reprogrammed virus to ovarian cancer which it successfully identified and destroyed.
“This is an exciting advance, offering real potential for patients with a variety of cancers.”
Once the virus enters the cancer cell it uses the cell’s machinery to replicate, producing many thousands of copies of itself, prior to bursting the cell and thereby destroying it in the process. The newly released viral copies can then bind and infect neighbouring cancer cells and repeat the same cycle, eventually removing the tumour mass altogether. The virus also activates the body’s natural immune system, helping it to recognise and destroy the malignant cells.
The reprogrammed virus is from a group of respiratory viruses called adenoviruses. The advantage of using these viruses is that they are relatively easy to manipulate and have already been safely used in cancer treatment.
The technique used to reprogramme the virus to identify the protein common to ovarian, breast, pancreatic, lung and oral cancers could also be used to manipulate it so that it would recognise proteins common to other groups of cancers.
Additional refinement to the viral DNA could also allow the virus to produce anticancer drugs, such as antibodies, during the process of infecting cancer cells. This effectively turns the cancer into a factory producing drugs that will cause its own destruction.
The research was carried out in a laboratory, using mice with ovarian cancer, and has not yet reached clinical trials. The next step is to test the technique with other cancers, with a view to starting clinical trials in five years’ time.
Dr. Catherine Pickworth from Cancer Research UK said: “It’s encouraging to see that this virus, which has been modified to recognise markers on cancer cells, has the ability to infect and kill ovarian cancer cells in the lab. Viruses are nature’s nanotechnology and harnessing their ability to hijack cells is an area of growing interest in cancer research. The next step will be more research to see if this could be a safe and effective strategy to use in people.”
The paper “Ad5NULL-A20 – a tropism-modified, αvβ6 integrin-selective oncolytic adenovirus for epithelial ovarian cancertherapies” is published in Clinical Cancer Research.
More information: Hanni Uusi-Kerttula et al. Ad5NULL-A20 – a tropism-modified, αvβ6 integrin-selective oncolytic adenovirus for epithelial ovarian cancer therapies, Clinical Cancer Research (2018). DOI: 10.1158/1078-0432.CCR-18-1089
