AT A GLANCE…
- Plezi Nutrition, a kids juice drink company, was launched by former First Lady Michelle Obama this week; Ms. Obama is the prior architect of the Let’s Move program.
- Jenny Craig, a forty year old, nutrition-forward weight loss company with over 1,000 stores, formally announced ‘…It’s with a heavy heart, we’re announcing the close of our business.’
- The American Association of Clinical Endocrinology, or AACE, published a consensus statement on ‘…Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity / Adiposity-Based Chronic Disease…’
- Results presented this week on over 55,000 patients with obesity, who underwent bariatric surgery, with the key finding that ‘…Bariatric surgery reduced the rate of de novo [or new] cancer diagnosis by half.’
EVENTS
- From my country of origin, there were some goings on this weekend at Westminster Abbey to crown King Charles III [and Queen Camilla]; conducted by the Archbishop of Canterbury.
NEWS
- Plezi Nutrition, a new company with a mission to ‘…be a driver of change and a model for how food and beverage brands can support the health of our next generation…’, was launched by former First Lady Michelle Obama this week, at the Wall Street Journal’s Future of Everything Festival. Mrs. Obama said, ‘…If you want to change the game, you can’t just work from the outside. You’ve got to get inside…’; and, ‘…you’ve got to find ways to change the food-and-beverage industry itself.’
- Plezi is a ‘…a no-sugar-added children’s drink…’ with an intent ‘…to replace sodas and other sugar-laden beverages. It contains water as the first ingredient along with fruit juices and stevia leaf extract…’
- For my part, I am skeptical. Though I applaud the intent, my concern is that this may be yet another example of getting a big name to front the brand of yet another juice drink for kids, in jazzy colorful bottles, and that there is not much of a broader impact on childhood obesity (and, the eight ounce serving size will likely be a challenge to kids who are used to much larger bottles).
- As mentioned, Jenny Craig embarked on a series of mass layoffs last week; and this week, formally announced ‘…It’s with a heavy heart, we’re announcing the close of our business.’ For those not in the know, ‘…Jenny Craig’s program provided nutritionally balanced menus, including entrees, desserts and snacks, designed to help people lose weight…’ I do think the mention from CNN that this is ‘…the latest sign of major changes in the weight-loss industry, brought on by popular new prescription diabetes drugs such as Wegovy, Ozempic, and Rybelsus…’ is too heavy-handed, and additive to the current hype on these drugs – we need a multimodal, whole-person approach.
- Stat has published a noteworthy article on Novartis’ approach to drug development in the obesity space [noting the context of past weight loss treatments having a ‘…checkered history of being ineffective or unsafe, and the few that did make it to market were commercial flops.’]. A few years ago, Novartis launched Versanius Bio with concomitant venture funding, a clinical-stage biopharmaceutical company bringing ‘…transformational treatments to people living with cardiometabolic disease…’. They are now undergoing clinical trials with bimagrumab, which was originally developed for muscle disorders; but now may be focused more on obesity. Its key differentiation is blockade of activin type II receptor (ActRII) to stimulate skeletal muscle growth, and promotion of excess adipose tissue loss to improve insulin resistance, in patients with overweight or obesity who had type 2 diabetes.
- I wonder if and when hashtags #bimagrumab and #ActRII will be as popular as the GLP-1 hashtags on TikTok and in Hollywood celebrity circles?
- More seriously, Nick Williams, a partner at Medicxi venture firm that invested in Versanius, refers to an ‘… incredible resurgence of interest in the (obesity) space, and it has also happened extremely quickly.’
- Relanis Therapeutics is an Italian start-up focused on ‘…an RNA-based treatment designed to inhibit microRNA called miR-22…’ to ‘…a reduction only in fat deposits, not lean muscle.’
- A good view of the landscape is that of ‘…roughly 80 obesity treatments that are in development, over half are GLP-1-based…’ There is also development based upon natural hormone production, including Swiss-based Aphaia with ‘…coated beads to transport glucose into the lower intestine…’, New-York based Kallyope, and Aardvark Therapeutics on bitter taste receptors in the gut.
- It seems that there are a ton of opportunities for development in the obesity drug space. My thoughts on this are fully aligned with the observation of Michael Nedelcovych, vice president of equity research at TD Cowen: ‘…Having a thriving obesity marketplace, even if it is dominated by large competitors, is probably a better thing for a small company as long as they have a differentiated offering.’
- In the UK, Kat Lay at The Times reports on the availability of Wegovy to be ‘…pushed back indefinitely, forcing millions of eligible people to wait for treatment.’ In fact, up to ‘…four million people in England are expected to be eligible for the drug…’ which, in my reckoning, at £75 per monthly dose would reach close to £4B in expenditure per year – or three percent of the total £150B UK budget for its National Health Service. [And take note, the monthly charge in the UK is a fraction of what Americans pay at $1,300/month].
- The article goes on to say that ‘…A spokesman for Novo Nordisk said they had “not confirmed a launch date for Wegovy in the UK”, but were working to make it available “as soon as possible”.’
- I am also concerned as to how many of the four million eligible will actually get the medication, how many of them will have adjunctive lifestyle and nutritional counselling, and how many of them will maintain their treatment after the two-year maximum prescription period. One to watch for sure!
- Similarly, CNBC reports from the US that Novo Nordisk was ‘… cutting the supply of starter doses of its obesity drug Wegovy in the U.S. as it struggles to keep up with surging demand.’ with shares subsequently down 7%. Chief Financial Officer Karsten Munk Knudsen told CNBC that ‘…We are careful not to launch faster than we can scale our supply base…’ which seems not only sensible, but necessary.
- The sulfur burp, an unpleasant side effect in a tenth of people enrolled in clinical trials for semaglutide, is discussed by Rachel Gutman-Wei in The Atlantic. In my opinion, this is likely due to the delayed gastric emptying effect of GLP-1 medications, and may also be due to a modification in the composition of gut bacteria – which can also lead to foul-smelling flatus… not seen any reports of that to date.
- Compounded or copycat versions of semaglutide are brought under the spotlight by Berkeley Lovelace Jr. in NBC News by a ‘…growing number of states are threatening to take legal action against pharmacies that make or dispense unauthorized versions of the weight-loss medications Ozempic and Wegovy’ in the face of growing shortages. Clamp downs are being enforced by ‘…state regulators that oversee pharmacies in Louisiana, Mississippi, North Carolina, and West Virginia.’ The key issue mentioned by Jim Yawn, the owner of Uptown Pharmacy, a compounding pharmacy in Madison, Mississippi is that ‘…patients may not always know what they are getting…’ which may be harmful, though there are no known reports of harm to date. Allison Schneider, spokesperson for Novo Nordisk weighed in too, with ‘…We will not tolerate the unauthorized and inappropriate usage of our brand trademarks by third parties.’
- The American Association of Clinical Endocrinology, or AACE, published a consensus statement on ‘…Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity / Adiposity-Based Chronic Disease…’ with support funding from Novo Nordisk. The article is long and academic in nature, though the first sentence of the main text is worth more than a brief ponder, ‘Obesity is a complex, multicausal, chronic disease with variable clinical phenotypes defined by abnormal or excessive adiposity…’
- The key definitions in Box 1 on weight bias, weight stigma, internalized weight bias, implicit weight bias, and explicit weight bias are a useful summary. And of further use is the statement on ‘…The paradigm shift from a weight/BMI-centric obesity diagnosis in which the emphasis is purely on weight loss to clinically based ABCD [Adiposity-Based Chronic Disease] that aims to improve health through prevention and treatment of complications underscores the fact to patients and health care professionals that this is a chronic disease and not a lifestyle choice.’
- The key takeaways for me are ‘…Obesity is a complex disease…’ and while ‘…obesity is not a lifestyle choice, lifestyle modifications are the critical foundation…’ to drive ‘…alterations in diet and physical activity, education, behavioral therapy, and supportive care from health care teams.’ I am passionate on the approach that a ‘…BMI-centric diagnosis of obesity is not appropriate, on its own…’ and to advance a ‘…complication-centric staging of ABCD can provide personalized interventions that match disease severity and the intensity of therapy.’ This is pretty much music to my ears and I am excited to engage further with colleagues at AACE too. The slide presentation is available here too.
OPINION
- Dr. David Ludwig from Boston, and Dr. Jens Holst from Copenhagen, Denmark, embark on their Viewpoint on childhood obesity in JAMA, or the Journal of the American Medical Association, with ‘Treatment focused on the root cause of disease generally achieves the best outcomes for efficacy and safety, a precept that has guided medical research and clinical practice for centuries.’ They reference the American Academy of Pediatrics (AAP) clinical practice guideline for the evaluation and treatment of children with obesity, such that it ‘…emphasizes weight loss drugs and bariatric surgery…’
- The authors explore the role of low glycemic load diets: ‘…Slower-digesting carbohydrates must travel farther down the intestinal tract before being fully absorbed, resulting in lower postprandial blood glucose levels and insulin secretion…’ in a mode of action that may be analogous to GLP-1 agonist drugs.
- Further, they reference a study of ‘…262 patients with type 2 diabetes treated with a ketogenic diet and intensive behavioral supports, weight had decreased by 12% vs 0.2% for a nonrandomized usual care group after 1 year.’ though fail to mention this was on adults, not children.
- The article also mentions the cost of GLP-1 medications, at individual and population levels, their appeared exacerbation of health care disparities, and the need for lifelong treatment.
- In reference to the opening sentence, the closing argument, if I may, is confusing and may be construed as harmful to state that ‘…for children, diet and lifestyle must remain at the forefront of obesity prevention and treatment.’ We need to develop multi-year programs of care, that do not pit GLP-1 medications against dietary interventions, or bariatric surgery against medication therapy, and the like. This is important, and timely – we need to drive research studies to develop and test multimodal and individualized care pathways for children and adults alike – and to do this without stigma or bias.
- ‘Employers are fielding a surge of demand from their workers for obesity care benefits — specifically, for a buzzy class of weight loss drugs — and it’s getting pricey…’ is the first sentence from Tina Reed at Axios Vitals. On GLP-1 drugs, Nadina Rosier, at Health Transformation Alliance, a cooperative of America’s largest employers, is quoted ‘…They went from being kind of non-existent in a top drug list to now in the top 25…’ The take home message is that ‘…Many employers are offering at least some coverage of GLP-1s for weight loss but are using a number of gatekeeping tools.’ including BMI requirements. In addition, what happens when an employee is on the drug, and loses weight into the normal BMI range – are they then no longer eligible?
- In the Wall Street Journal, David Wainer examines the corporate aspects of GLP-1 blockbuster drugs, in parallel to ‘…the cholesterol-drug revolution starting in the 1990s. Statins such as Lipitor and Crestor created a new category of medicine and generated billions of dollars for their manufacturers because the market was huge…’ He adds ‘…during its heyday, Pfizer’s Lipitor became the bestselling drug of all time, generating peak annual sales of $13 billion.’ which pales into comparison for the $100B plus projected annual market of GLP-1 medications.
- The burgeoning obesity medication market continues to be in super-hype mode, with Bill Sessa, chief scientific officer at Pfizer’s Internal Medicine Research Unit quoted ‘…We’re going full guns on this…’ and ‘…If we can accelerate, we will.’ In addition, Dr. Jamie Kane, chief of obesity medicine at New York’s Northwell Health, ‘…called the new weight-loss drugs very promising.’ I am, however, concerned with Pfizer’s approach to oral drugs – while this might make common sense, in lieu of a weekly subcutaneous injection, I am concerned about the degree of medication adherence which is 50% at best for most drug types.
DATA
- From Digestive Diseases Week in Chicago, the most prestigious meeting in the world for gastrointestinal professionals, Dr. Vibhu Chittajallu, a gastroenterology fellow at Case Western Reserve University and University Hospitals Cleveland presented results on over 55,000 patients with obesity, who underwent bariatric surgery, and compared them to a matched non-surgical group. The key finding was that ‘…Bariatric surgery reduced the rate of de novo [or new] cancer diagnosis by half. At ten years following the index date, the cumulative incidence of obesity-related cancers was 4% in the surgery group and 8.9% in the non-surgery group…’ which unsurprisingly is a statistically significant finding. The prevalence of cancers of the breast, colon, liver, pancreas, ovaries, thyroid gland, and multiple myeloma that affects the blood cells, was greatly reduced, at up to ten years after surgery. Dr. Chittajallu was quoted on the contemporary focus ‘…of bariatric surgery to be weight loss and the physical and psychological benefits that come with that…’ with a lesser consideration ‘…on how significant this weight loss can be to overall health, including cancer risk.’
- Academic colleagues from Medical College of Georgia, Augusta University, ask ‘What are the odds of high obesity-related cancer mortality rates in US counties with low-income food desert or food swamp environments?’ in JAMA Oncology, a peer-reviewed Journal. They note that obesity-related cancers account for 40% of all cancers in the US, and sought to ‘…analyze the association of food deserts [areas with less access to grocery stores] and food swamps [areas with higher access to fast food] with obesity-related cancer mortality in the US.’ From 3,038 US counties, high obesity-related cancer mortality rates were associated with higher percentages of non-Hispanic Black residents, persons older than 65 years, higher poverty rates, higher adult obesity rates, and higher adult diabetes rates. Importantly, there was ‘…a 77% increased odds of having high obesity-related cancer mortality rates among US counties or county equivalents with high food swamp scores’, which is pretty remarkable though just as understandable. The study provides a terrific overview of social determinants of health, and the impact upon obesity-related cancer mortality. The take home message from the authors that we need more ‘…sustainable approaches to combating obesity and cancer and establishing access to healthier food, such as creating more walkable neighborhoods and community gardens’ is a great start; but a ton more work exists to do for us all, to achieve better outcomes for those who need them the most.
Kind regards, Raj
