NIH reviews Obesity in Kids; Altimmune and Pfizer report on new Obesity Drug Trials; Novo CEO wants Shared Risk Pricing for Wegovy; Ozempic vs. Mounjaro – let the Head-to-Head games begin.
The National Institute of Health, or the NIH, held a two-day meeting this week on pharmacotherapy for obesity in children and adolescents.
Pfizer announced data for their in-house GLP-1 agonist drug danuglipron, with ‘…mean placebo-adjusted weight reductions ranging from -8% to -13% at 32 weeks…’
Altimmune announced ‘…results from its 48-week MOMENTUM Phase 2 obesity trial of pemvidutide…’, with mean weight losses of up to 15.6%, and 30% of those achieving 20% in weight loss.
A ‘Joint Statement in Support of Closing Gaps in the Drug Approval Process and Drug Labeling for People with Obesity…’ was published this week.
Novo Nordisk CEO, Lars Fruergaard Jørgensen, said the company might offer flexible pricing on Wegovy in reporting from Prarthana Prakash at FORTUNE.
The Washington Post asks ‘How to make powerful new obesity drugs available to all…’ and in essence to ‘…bring a large share of the population back to good health.’
Alan Goforth writes in Benefits Pro on the staggering costs of new GLP-1 medications such that ‘…expenditures for U.S. adults would soar by more than $1 trillion if all obese individuals initiated a treatment plan.’
Truveta announced ‘…new comparative effectiveness research exploring weight loss among patients taking semaglutide (Ozempic) and tirzepatide (Mounjaro).’
A comprehensive review of obesity management in adults is published in JAMA, or the Journal of the American Medical Association.
EVENT
The National Institute of Health, or the NIH, held a two-day meeting this week on pharmacotherapy for obesity in children and adolescents – a topic close to my heart as I led the initiation of the adolescent bariatric surgery program at Children’s Hospital of Philadelphia, over ten years ago, in 2013.
Major themes at the NIH were focused upon managing the whole person, outcomes beyond weight loss, equity and access to care, and better science.
NEWS
Pfizer announced data for their in-house GLP-1 agonist drug danuglipron, with ‘…mean placebo-adjusted weight reductions ranging from -8% to -13% at 32 weeks…’ though ‘…High discontinuation rates, greater than 50%… across all doses.’
The phase 2b clinical trial studied the twice-daily oral formulation in patients with obesity, at a BMI of greater than 30, and no current or prior diagnosis of diabetes.
Of interest, the press release mentions ‘…twice-daily danuglipron formulation will not advance into Phase 3 studies.’
Mikael Dolsten MD PhD, Chief Scientific Officer & President, Pfizer Research and Development stated ‘…We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile…’ with ‘…pharmacokinetic data anticipated in the first half of 2024.’
STAT News coverage from Andrew Joseph and Elaine Chain kicks off with ‘…Pfizer on Friday said it was stopping development of a twice-daily oral obesity medication after an underwhelming clinical trial.’
Indeed, the ‘…weight reductions were smaller than those seen in trials of rival medicines… and a high rate of patients experienced side effects and dropped out of the trial.’
The market did not take this news favorably, with ‘…Pfizer’s share price down about 6%, cutting nearly $10 billion from the company’s valuation.’
Both Eli Lilly and Novo Nordisk are also working on oral GLP-1 medications, either as modifications of their current formulation, or for Eli Lilly, as a new ‘…once-daily GLP-1 pill, orforglipron, that led to 15% weight loss in a 36-week Phase 2 study.’
Altimmune, a clinical-stage biopharmaceutical company focused on the development of novel peptide-based therapeutics for the treatment of obesity and liver diseases, announced ‘…results from its 48-week MOMENTUM Phase 2 obesity trial of pemvidutide…’, a GLP-1/glucagon dual receptor agonist.
From almost 400 patients, with a mean BMI of 37 of whom three-quarters were female, some achieved mean weight losses of up to 15.6%, primarily those on the highest 2.4mg dose, at week 48, with 30% of those achieving 20% in weight loss.
One in four patients on the drug did not complete the trial, though the ‘…majority of adverse events were predominantly mild to moderate in severity.’
Dr. Scott Harris, Chief Medical Officer of Altimmune said ‘…the trajectory of weight loss at the end of treatment with the 2.4 mg dose suggests the potential for greater weight loss with continued treatment.’
CEO Vipin K. Garg added ‘…This is an important day for Altimmune and we couldn’t be more pleased with these results…’ which was supported by investors with a hike in their stock price of 40%.
A ‘Joint Statement in Support of Closing Gaps in the Drug Approval Process and Drug Labeling for People with Obesity…’ was published this week and co-signed by the Obesity Action Coalition, The Obesity Society, the Stop Obesity Alliance, the Obesity Medicine Association, and the American Society for Metabolic and Bariatric Surgery.
The statement urges the ‘…U.S. FDA to close gaps in the testing and approval process for drugs intended for use by people with obesity for conditions other than obesity.’
For example, ‘…there is no requirement that new prescription drugs be shown to be safe and effective for people with obesity before FDA approves them…’ including medications for emergency birth control, depression, and pain relief.
Joe Nadglowski, President and CEO of the OAC said ‘…Everyone deserves to know the drugs they use are safe and effective. The FDA and drug companies need to take action now.’
Reuters reporter Patrick Wingrove refers to Novo Nordisk in that it ‘…sued one compounding pharmacy and refiled a lawsuit against another after finding their products claiming to contain the active ingredient for its in-demand weight-loss drug Wegovy were impure, some by as much as 33%.’
The drugs were ‘…tested from Wells Pharmacy and Brooksville Pharmaceuticals, both based in Florida.’
Jason Brett, a Novo Nordisk executive said ‘…Compounded products do not have the same safety, quality and effectiveness assurances as FDA-approved drugs, and adulterated and misbranded injectable compounded drugs may expose patients to significant health risks.’
Novo Nordisk CEO, Lars Fruergaard Jørgensen, said the company might offer flexible pricing on Wegovy in reporting from Prarthana Prakash at FORTUNE.
He is ‘…open to what types of arrangements we can make with health care systems that could help them serve the patients who need it the most…’ with an intent to ‘…to share that risk to get going.’
OPINION
Without much surprise or fever, ‘…Lilly is enrolling for a cardiovascular outcomes trial to examine tirzepatide’s impact on heart health in patients without type 2 diabetes…’ with the expectation of results in 2027, from Patrick Wingrove at Yahoo Finance.
And further, there is a ‘…head-to-head trial pitting Zepbound against Wegovy in overweight or obese patients with other weight-related health issues…’ with data expected in 2025.
Dr. Edmond Wickham, an endocrinologist Virginia Commonwealth University ‘…would anticipate that the cardioprotection with Wegovy would extend to Zepbound.’
The Washington Post asks ‘How to make powerful new obesity drugs available to all…’ and in essence to ‘…bring a large share of the population back to good health.’
Priced at over $1,000 per month, the necessity for lifelong treatment, and that almost one-half of the US adult population are eligible, bring onward challenges and opportunities.
The prices are subject to negotiation, by insurers ‘…buying the medicines in bulk, guaranteeing drugmakers large markets…’ such as for state Medicaid programs.
In a caveated closing, the authors note ‘…The weight-loss drugs are not miracle cures… [though] are one weapon in the obesity fight… [that] may be powerful enough to make a big difference.’
Nikhil Krishnan, outspoken and funny writer of the Out-Of-Pocket newsletter reviews GLP-1 drugs, in terms of weight loss outcomes, cardiovascular risk reduction, side effects and adherence.
The four pushbacks focus upon the US food system, the role of diet and exercise, body image issues, and unkown long-term risks.
Nikhil thinks that ‘GLP-1 manufacturers are going to get similarly creative in working with consumer companies to increase their brand awareness and market share…’ with the possibility of a Zepbound sports arena.
I agree with the notion of more focused markets, the need for wraparound services, inclusive or post-market monitoring.
From a cost perspective it is spot on that ‘…most payers are trying to figure out all the ways to NOT cover it… because people continuously churn off plans when they switch employers.’
Thanks Nikhil.
Dr. Sachin Jain, President and CEO of SCAN Group and Health Plan, a $3.4B non-profit entity that serves over 220,000 patients, writes in Forbes on his ‘Top 10 Healthcare Industry Predictions For 2024.’
Generally interesting to review, though specifically is #7 that ‘…Ozempic, Mounjaro, and other GLP-1’s will grow in popularity.’
We will see ‘…even more people will begin taking GLP-1’s… [with] more real-world studies of their effectiveness… [and] some new questions raised about their safety and effectiveness.’
I am surprised, though not surprised, aligned with Sachin’s role at SCAN Health, that he does not mention the pricing and access issues prevalent and likely to continue.
CVS Caremark, the pharmacy benefit management entity for CVS Health, ‘…recommends an evidence-based approach to efficiently manage the dynamic GLP-1 category…’ in a sponsored article from Healthcare Brew.
With a focus to ‘…evaluate the unique health needs of their covered populations…’ there should be an ability to ‘…combine[s] coverage, cost, and care.’
There are a ‘…number of utilization management options, ranging from less to more restrictive…’ with dials such as ‘…quantity limits, step therapy, and prior authorization.’
Despite the focus on GLP-1 medications per se, I am delighted to take note of a comprehensive care management program, most effective ‘…when dosed appropriately and paired with lifestyle changes including diet and exercise…’ to ‘…help control costs and ensure that weight loss is sustainable.’
Alan Goforth writes in Benefits Pro on the staggering costs of new GLP-1 medications such that ‘…expenditures for U.S. adults would soar by more than $1 trillion if all obese individuals initiated a treatment plan.’
Dr. Byron Crowe, chief medical officer for Solera, a marketplace of sorts for health plans and employers to leverage digital health solutions, recognizes the price point, mass eligibility, and the need for lifelong treatment.
A recent survey by the Business Group on Health states that ‘…46% of large employers covered GLP-1s for weight loss in 2023, another 3% plan to add coverage in 2024 and 13% are considering adding them for the 2025 or 2026 plan years.’
Becker’s Spine Reviewnotesorthopedic surgeons will need to ‘…either double their total joint arthroplasty caseload or the number of surgeons will need to increase by 10% every five years to meet the growing demand for surgery…’ as GLP-1 drugs ‘…make it possible for patients with BMI too high for surgery to lose weight.’
Ravi Bashyal MD, at NorthShore Orthopedics in Chicago, has ‘…seen more patients recently that are able to now have surgery because they’ve had additional help [losing weight].’
On the industry side, Lisa Kloes, general manager and vice president of Stryker’s knee business, thinks ‘…weight loss drugs could make it possible for patients with BMI too high for surgery to lose weight…’ and ‘…help implant volumes.’
Food is medicine, or the provision of free, nutritious food through the health care system, is reviewed by Drs. Moran and Roberto in JAMA this week.
The authors note that ‘…robust evidence to support significant salutary benefits from the wide array of food is medicine programs being offered is lacking…’ and are ‘…skeptical that food is medicine programs will lead to long-term improvements in diet or health.’
A more pragmatic focus is to change ‘…food industry behavior to ensure that unhealthy foods are not ubiquitous and not as cheap and heavily marketed while ensuring that our existing nutrition assistance programs are accessible and health promoting.’
Yasmin Tayag at The Atlanticwrites on anti-obesity medications that ‘…anyone attempting to get a prescription will inevitably confront the same obstacle: their body mass index, or BMI…’ to such an extent that ‘BMI Won’t Die.’
Tayag refers to BMI as the ‘…decrepit car you keep driving because it still sort of works and is too much of a hassle to replace.’
Rightly so, ‘…BMI becomes troubling when it is all that doctors see…’ though the current state is that ‘…obesity drugs make this metric even more consequential.’
The FDA approval of semaglutide ‘…for children ages 12 years and up, in combination with diet and exercise…’ and Mounjaro ‘…in November for chronic weight management in adults, under the brand name of Zepbound…’ are highlighted.
Newer drugs in pipeline are mentioned, namely retatrutide with an almost 25% total weight loss, survodutide, oral pill orforglipron, and a high-dose oral pill of semaglutide.
A 24% lower incidence of cancer after bariatric surgery, increasing popularity of bariatric surgery in kids with obesity, and a shift away from BMI as a key tenet of obesity care are noted too.
DATA
Truveta, with data from over 100 million patients in all 50 states from more than 800 hospitals and 20,000 clinics, announced ‘…new comparative effectiveness research exploring weight loss among patients taking semaglutide (Ozempic) and tirzepatide (Mounjaro).’
The analysis reviewed data from over 40,000 patients with overweight or obesity; over two-thirds were white or female, with close to 7 out of 10 of the population suffering from type 2 diabetes, raised lipids or hypertension.
Those on tirzetapide were ‘…1.8 times more likely than those taking semaglutide to achieve 5% weight loss…’ and almost surprisingly, ‘…three times more likely than those taking semaglutide to achieve 15% weight loss.’
A reminder that this is not clinical trial data, but a real-world analysis of outcomes, in that ‘…At one year, the mean percentage change in body weight was -15.2% for those taking tirzepatide versus -7.9% for those taking semaglutide.’
The full Truveta research manuscript is posted for review.
On deeper evaluation, there were just over 40% of those on Eli Lilly’s tirzetapide, or Mounjaro that lost over 15% of their total body weight at one year, versus just shy of 20% of those on Novo Nordisk GLP-1 medication semaglutide, or Ozempic.
More interestingly, on the other end of the spectrum, 18% or almost 1 in 5 patients on tirzetapide did not lose more than 5% of their total body weight at one year; and for semaglutide, 35%, or over 1 in 3 patients had weight loss of less than or equal to 5%.
The two caveats are to the study population, the majority of whom were female, white and suffered from type 2 diabetes – we know that weight loss in those with diabetes is inferior to those without.
Despite this, there are somewhere between 1 in 3 and 1 in 5 patients who are on a GLP-1 drug, that do not achieve significant weight loss – a 5% level of weight reduction is that achievable and related to intensive lifestyle therapy, consisting of a low-calorie diet, routine aerobic exercise, and regular counselling sessions – all of which can be delivered at a much lower cost than the price of a GLP-1 drug.
An additional strength of the study was that almost 1 in 4 of the patients had a history in the past two years of major depressive disorder – with clinical trials excluding a large proportion of such patients.
In furtherance, the gastrointestinal side effects displayed a similar profile between the two groups.
And I do wish the authors could have also reviewed resolution of chronic diseases such as type 2 diabetes, hypertension and sleep apnea in their cohort – or perhaps this is part of an onward analysis?
The Truveta GLP-1 head-to-head study is covered by Annika Kim at CNBC, in that the ‘…blockbuster diabetes drug Mounjaro is more effective for weight loss than another highly popular diabetes treatment, Ozempic, in overweight or obese adults.’
Neither Novo Nordisk or Eli Lilly were involved in the study, and take note that this was a real-world analysis, as opposed to ‘…head-to-head clinical trials in that population are not yet available.’
Dr. Nick Stucky, an author of the study and vice president of Truveta Research, said ‘…This study can help to inform patient care and outcomes today, not months from now.’
A comprehensive review of obesity management in adults is published in JAMA, or the Journal of the American Medical Association, through review of ‘…9 clinical practice guidelines from relevant medical associations published in the last 10 years….’ in addition to over 3,000 obesity-related articles.
As we well know, ‘…by 2030, 48.9% of US adults will have obesity and that racial differences in rates of obesity will increase.’
The risk factors, pathophysiology, diagnosis and classification of obesity are described.
The 5As (Assess, Advise, Agree, Assist, Arrange) can guide shared decision-making, underpinned by setting personal weight-loss targets.
Intensive behavioral lifestyle therapy, nutrition, physical exercise, pharmacotherapeutic and surgical interventions are reviewed as ‘…Components of Comprehensive, Evidence-Based Weight Management for Adults With Obesity…’ and summarized in table 2.
Follow-up and long-term obesity management ‘…is difficult and may be supported by continued clinical intervention.’
