DaVita challenged by GLP-1 outcomes for kidney disease; the stock market is getting Ozempic’ed; more employers end GLP-1 coverage; under-representation of people with obesity in clinical trials.

AT A GLANCE

• DaVita Inc. issued a statement in response to Novo Nordisk in relation ‘…to its FLOW study that sought to demonstrate that Ozempic delays progression of chronic kidney disease (CKD) and lowers the risk of kidney and cardiovascular mortality.’
• Retatrutide, an Eil Lilly drug yet to be approved by the FDA, boasting ‘…Phase 2 trial results that showed the drug led to an average weight loss of up to 24% over 48 weeks…’ is already being sold online, according to Rolfe Winkler at The Wall Street Journal.
• ‘The stock market is getting Ozempic’ed…’ is the lead story from Matthew Fox at Business Insider.
• ‘Minneapolis-based Hennepin Healthcare is ending coverage for Wegovy and other injectable weight loss drugs from its employee health insurance plan next year…’ in reporting from Jakob Emerson at Becker’s Hospital Review.
• Christina Chow, the head of research at Emerald Lake Safety, an institution that conducts independent research to make pharmaceuticals safer was quoted in STAT News that ‘…People with obesity are underrepresented in clinical trials for drug approval.’
• Dr. Thomas Wadden from the University of Pennsylvania and colleagues publish in Nature Medicine on 579 subjects who had achieved >5.0% weight reduction, and were then randomized to GLP-1 medication tirzetapide, or a dummy placebo drug, for 72 weeks.
• Dr. Lee Kaplan, well known clinician and obesity researcher from Boston presented data from the SURMOUNT-1 trial of Eli Lilly drug Mounjaro, in terms of variation in weight loss across the enrolled subjects.

EVENTS

• ObesityWeek convened over 2,000 attendees in Dallas, Texas, under the conference theme CONNECTIONS. There were over 240 scientific presentations, many of which are detailed in the DATA section, with key lectures from clinician scientist heavyweights Drs. Lee Kaplan from Boston, Ania Jastreboff at Yale University.

NEWS

• • DaVita Inc. that provides kidney dialysis services through a network of almost 3,000 outpatient dialysis centers in the United States, serving over 200,000 patients, issued a statement in response to Novo Nordisk in relation ‘…to its FLOW study that sought to demonstrate that Ozempic delays progression of chronic kidney disease (CKD) and lowers the risk of kidney and cardiovascular mortality.’
    • Dr. Jeff Giullian, chief medical officer for DaVita Inc. believes ‘…there may be limited application of the FLOW study findings to the overall CKD patient population.’
    • In furtherance, DaVita ‘…estimates that fewer than 10% of all current CKD patients would have this combination of factors…’ in reference to the entry criteria for patients to enroll in the FLOW study.
    • And second, the relevance to DaVita of findings on study endpoints that are related to cardiovascular versus kidney complications.
  • ‘Ozempic is arguably the world’s most famous drug…’ writes Madison Muller in Bloomberg Businessweek.
    • Indeed, the ‘…far-reaching benefits of Ozempic and other medicines in the same class… appear to have a protective effect on the heart, liver and kidneys in addition to helping people lose weight…’ and there is ‘…reason to believe GLP-1s could help combat substance abuse or even Alzheimer’s disease.’
    • Matthew Taylor, an analyst who covers medical-device stocks for Jefferies LLC, is quoted ‘…The market has reached a point of near peak hysteria regarding the impact of GLP-1s.’
  • ‘Eli Lilly & Co. is planning to test its diabetes drug Mounjaro for patients six and up with obesity…’ in reporting at Bloomberg Businesweek.
    • Nadia Ahmad, Eli Lilly’s associate vice president of medical development for obesity is quoted ‘We are certainly committed to innovation in this space that’s going to address all segments of the population that’s affected.’
    • With one in five kids in the US suffering from obesity, ‘…experts say the availability of safe, effective medications is a game-changer, particularly as US childhood obesity rates have tripled in the last decade.’
  • Retatrutide, an Eil Lilly drug yet to be approved by the FDA, boasting ‘…Phase 2 trial results that showed the drug led to an average weight loss of up to 24% over 48 weeks…’ is already being sold online, according to Rolfe Winkler at The Wall Street Journal.
    • Richard DiMarchi, a professor of chemistry at Indiana University said ‘…the drug can be made fairly easily by a trained chemist with the right equipment.’ This is ‘…because Lilly has disclosed retatrutide’s chemical structure, which it is required to do to secure patent protection.’
    • More critically, unauthorized entitires will sell ‘…research-grade versions of the drug, which are sometimes used by academics in animal testing…’ and may not be safe for human use.
    • Elizabeth Knupp, a 44-year-old nurse from California ‘…decided to try retatrutide because she hopes the drug will be even more effective…’ than Mounjaro, leading her to purchase ‘…retatrutide in late August from Qingdao Sigma Chemical…’, a Chinese company that sells steroids, peptides, weight-loss drugs and more.
    • This is scary, potentially harmful, and totally wrong… though I also empathize with patients such as Knupp in their desperation to lose weight and lead a healthier life.
  • ‘The stock market is getting Ozempic’ed…’ is the lead story from Matthew Fox at Business Insider.
    • The share price plunges of kidney dialysis companies DaVita and Fresenius in response to the FLOW trial of chronic kidney disease patients on GLP-1 medication, Novo Nordisk becoming Europe’s most valuable company, and drops in value of CPAP manufacturers, insulin delivery systems, and heart valve devices, have also spread to food companies, like Costco and Walmart.
    • More broadly, ‘…even plane operators could get more efficient with lower-weight customers driving fuel savings.’
  • Ilant Health, a virtual obesity treatment company, launched this week with $3 million in funding.
    • The company ‘…helps identify members and employees who would benefit from obesity treatment and matches those patients to the care that is best for them.’
    • Elina Onitskansky, CEO of Ilant and a bariatric surgery patient herself, stated ‘…Treatment only works if you’re on it long term, when you’re actually not just losing weight initially, but maintaining the weight loss.’
  • Novo Nordisk has ‘…joined forces with GE HealthCare to develop a drug-free, noninvasive treatment for obesity and Type 2 diabetes…’ from Andrea Park at Fierce Biotech.
    • Peripheral-focused ultrasound technology, or PFUS, ‘…sends out soundwaves to activate specific areas of the nervous system, with an aim of modulating certain nerve responses.’
    • In a past study, PFUS was used to ‘…stimulate metabolic sensory neurons in the livers of mice over the course of eight weeks was associated not only with significant weight loss but also a reduction in inflammation and other obesity-related complications.’
  • ‘Minneapolis-based Hennepin Healthcare is ending coverage for Wegovy and other injectable weight loss drugs from its employee health insurance plan next year…’ in reporting from Jakob Emerson at Becker’s Hospital Review.
    • David Hilden, MD, chair of the health system’s medical department said ‘…We spent like $7 million on one drug, and that’s a lot.’
    • Indeed, ‘…St. Louis-based Ascension dropped coverage for weight loss drugs from its employee health plan in July, and the University of Texas System in Austin ended coverage under its employee and retiree health plans in September, citing high costs and low adherence rates.’
    • CEO at UnitedHealth Grooup, Andrew Witty said in a direct blow to drug manufacturers ‘…We recognize that has potential benefits, but we’re struggling, and frankly our clients are struggling, with the list prices which have been demanded of these products in the U.S., which are running at about 10 times the level of prices paid in Western Europe.’
    • More to come on this front, with additional self-insured employers balking at the costs of so-called the game changer drugs.
  • Business Insider has learned ‘…Weight-loss startup Calibrate is selling itself to the private equity firm Madryn Asset Management…’ that was ‘…announced in a Slack message to the startup’s staff on Friday.’
    • Calibrate, a virtual weight loss clinic with GLP-1 medication prescriptions has ‘…raised more than $160 million from investors…’ though recently ‘…faced complaints from its members, many of whom have reported delays in getting responses from the startup’s staff and trouble getting their weight-loss prescriptions.’

OPINION

• Christina Chow, the head of research at Emerald Lake Safety, an institution that conducts independent research to make pharmaceuticals safer was quoted in STAT News that ‘…People with obesity are underrepresented in clinical trials for drug approval.’
  • A study presented at ObesityWeek in Dallas reviewed ‘…201 drug approval studies in clinicaltrials.gov that occurred in 2022, and found that 64% did not include weight or BMI-based inclusion/exclusion criteria.’
  • And further, ‘…of the 72 studies that did have a weight or BMI-based inclusion/exclusion criteria, 75% of the trials used the criteria to exclude patients with obesity.’
  • This is important from a stigma perspective, but also because people with obesity may take longer to achieve therapeutic levels of certain drugs due to their altered physiology, and may also persist in their bodies for longer due to delayed excretion. For example, ‘…Rexulti, a drug that is indicated for use in patients with schizophrenia and depression… took extensively longer to reach effective levels in people with obesity.’
• Lotte Bjerre Knudsen is profiled in STAT News this week, as the scientist that ‘…made Novo Nordisk an obesity-drug powerhouse.’
  • Knudsen is credited to have ‘…created a longer-lasting analog of GLP-1 that became liraglutide, a medication approved in 2010 and sold as Victoza that helped diabetes patients control their blood sugar and lose weight…’ and the precursor to semaglutide.

DATA

• Dr. Thomas Wadden from the University of Pennsylvania and colleagues publish in Nature Medicine on 579 subjects who had achieved >5.0% weight reduction, and were then randomized to GLP-1 medication tirzetapide, or a dummy placebo drug, for 72 weeks.
  • Those in the GLP-1 group achieved an additional 18.5% weight loss, compared to 2.5% weight gain in the control arm.
  • Overall, 806 subjects enrolled for intensive lifestyle therapy for a 12-week period, of whom just over two-thirds [72%] achieved over 5% total weight reduction.
  • The 12-week lifestyle intervention consisted of eight in-person lifestyle counseling sessions, calorie reduction diet, and at least 150 min of moderate-intensity physical activity per week, with 3-day diet and exercise logs before each counseling visit.
  • Of note, 1 in 5 or just over 20% of patients on tirzetapide, also known by the brand name Mounjaro, discontinued the drug too.
  • The authors rightly note ‘…individuals with overweight or obesity who have lost approximately 5–10% of their body weight with supervised lifestyle intervention – or potentially through their own self-directed diet and exercise efforts – could expect to achieve further clinically meaningful weight loss with the addition of tirzepatide.’ And further that the ‘…cumulative 24.3% reduction in body weight achieved with intensive lifestyle intervention, followed by tirzepatide, approximates the 1 year weight loss induced with sleeve gastrectomy.’
  • I am really excited by this approach, to develop a multimodal approach to care for people with obesity, such that the ‘…sequential use of these interventions appeared to produce additive weight loss that approached the combined results of each intervention used alone.’
  • It would have been interesting to note what would have happened had the one-third of patients who did not achieve over 5% total weight loss from the 809 subjects, been offered tirzetapide – would they have had an inferior degree of weight loss?
  • Essentially, has this study also opened the door to risk stratification of individuals who do well with lifestyle therapy, and then do even better with anti-obesity medication?
• In reporting from Business Insider, Gabby Landsverk quotes Dr. Thomas Wadden’s press release, in his role as lead author, past president of the Obesity Society and professor of psychology in psychiatry at the Perelman School of Medicine at the University of Pennsylvania that ‘These are extraordinary findings.’
• Jonel Aleccia at abc News adds from Dr. Wadden that the ‘…study says that if you lose weight before you start the drug, you can then add a lot more weight loss after.’
  • Dr. Caroline Apovian who treats obesity at Brigham and Women’s Hospital ans was not involved in the study goes further in that ‘…We’re doing a medical gastric bypass…’ which is remarkable.
• Robert Kushner, MD, of Northwestern University Feinberg School of Medicine in Chicago, reported at the ObesityWeek annual meeting ‘…People taking antidepressants lost a similar amount of weight on semaglutide 2.4 mg (Wegovy) compared with those not taking antidepressants.’
  • To explain, several antidepressants can lead to weight gain as a side effect of therapy; Dr. Jack Yanovski, chief of the section on growth and obesity at the NIH Intramural Research Program, noted that ‘…it’s really important that we understand what goes on in patients with depression.’
• Research was presented by Dr. Donna Ryan, of Pennington Biomedical Research Center in Baton Rouge, Louisiana from the ‘…Calibrate telehealth program, including video visits plus asynchronous check-ins and messaging, uses GLP-1 medications and intensive lifestyle interventions, with one-on-one coaching and digital tracking and medical treatment provided by board-certified physicians.’
  • At one year ‘…there was an average weight loss of 16.2% of body weight, with results sustained up to 24 months…’ to 17.2% total weight loss. There were almost 13,000 subjects include in the study, from a total of 30,000 Calibrate members from across all 50 states.
• Dr. Lee Kaplan, well known clinician and obesity researcher from Boston presented data from the SURMOUNT-1 trial of Eli Lilly drug Mounjaro, in terms of variation in weight loss across the enrolled subjects.
  • In the trial, ‘…people on the drug lost on average 21% of their body weight, but there was a wide distribution of responses — over 5% of participants taking the treatment lost just 5%-10% of their weight, while another subset lost 35%-40%.’
  • Whilst the focus of Kaplan’s research was to identify the role of the melanocortin-4 (MC4) receptor, in terms of a genetic basis to weight loss, the results did not bear fruit.
  • However, I certainly believe there is a data-based approach to tailored or personalized obesity care, to guide the right patient, with the right intervention, and at the right time, to achieve the desired outcome.  

Kind regards, Raj