Tag: Novo Nordisk

Tirzepatide Beats Semaglutide in Weight Loss

Posted on by Viktor Zarev

Has a king of the GLP-1s finally been crowned? Full results from the SURMOUNT-5 trial published in NEJM seem to suggest that Eli Lilly’s tirzepatide (Zepbound/Mounjarno) could be better than Novo Nordisk’s semaglutide (Wegovy/Ozempic).

  • Both tirzepatide and semaglutide are highly effective medications for obesity management. 
  • However tirzepatide’s efficacy compared to semaglutide in obese adults without T2D was unknown until now.

Weighing the weight loss benefits of each drug, SURMOUNT-5’s researchers randomized 751 obese patients without T2D to receive either tirzepatide (10mg/15mg) or semaglutide (1.7mg/2.4mg) and found that patients on tirzepatide lost far more weight after 72 weeks.

  • The average weight loss at week 72 was significantly greater with tirzepatide compared to semaglutide (−20.2% vs. −13.7%). 
  • Patients on tirzepatide also lost more waist circumference (−18.4 cm vs. −13.0 cm).
  • Tirezepatide also had fewer discontinuations due to gastrointestinal events (2.7% vs. 5.6%) and fewer vomiting adverse events (15.0% vs. 21.3%).

While Lilly takes the weight loss cake, the GLP-1 game is quickly becoming about more than just raw weight loss, with several studies in the last few years touting the cardiac benefits of Novo’s semaglutide.

  • TRANSFORM-AF recently showed that semaglutide could help reduce AFib events.
  • The STRIDE trial uncovered that semaglutide improves the impact of PAD.
  • The SELECT trial found that overweight or obese patients with CVD reduced their risk of MACE on semaglutide.
  • Results from SELECT were so strong that Novo eventually used them to secure FDA approval and payor reimbursement for semaglutide’s CV event reduction indication.

Meanwhile, tirzepatide’s SUMMIT trial found it reduced mortality risks in HFpEF patients with obesity, but Lilly has since pulled its request to the FDA to approve tirzepatide for HF.

  • It’s also worth noting that SURMOUNT-5 and the other SURMOUNT trials are funded by Lilly.

The Takeaway

SURMOUNT-5 confirms what many have suspected for a while – tirzepatide leads to more weight lost than semaglutide in the same amount of time. Whether or not that advantage will sway prescribers and patients remains to be seen.

Wegovy Gains Expanded Approval for CVD Risk Reduction

Posted on by Jake Fishman

The hottest drug class in the world just got even hotter after the FDA approved Novo Nordisk’s weight-loss drug Wegovy for cardiovascular event risk reduction, opening new cardiology-focused routes for GLP-1 care and coverage.

  • Wegovy’s expanded FDA approval now supports its use for the reduction of major adverse cardiovascular events in obese or overweight adults with established CVD.
  • Semeglutide was already approved for diabetes (via Ozempic) and weight loss (via Wegovy), although payors have largely resisted covering non-diabetic patients.

The expanded approval could have a major cardiology impact, making cardiologists a key driver of Wegovy prescriptions, while making CVD risk reduction a primary way to increase coverage of the GLP-1 (vs. out-of-pocket or on/off-label diabetes care).  

More importantly, it could lead to significantly better cardiovascular outcomes for these patients. The SELECT trial, which served as the basis for this expanded CVD approval, showed that Wegovy slashed patients’ major cardiac event risks by 20% over five years, while cutting non-fatal heart attacks by 28% and reducing cardiovascular mortality by 15%.

  • The SELECT trial included the types of patients who are most likely to be impacted by Wegovy’s expanded approval: non-diabetics with obesity and established CVD.

Considering that the overwhelming demand for GLP-1s gives Novo Nordisk little reason to reduce Wegovy’s $1,350 monthly price, the expanded coverage should further increase healthcare’s overall GLP-1 costs. 

  • However, this expansion could serve as a case study for whether GLP-1s’ ability to reduce future cardiovascular events makes both clinical and financial sense over the long term.

Wegovy’s CVD approval might also pave the way for similar expansions for Lilly’s tirzepatide (Mounjaro and Zepbound), which has shown even stronger weight loss results than semeglutide, and is now being evaluated for its cardiovascular benefits in clinical trials. 

The Takeaway

To many people, Wegovy’s expanded FDA approval is an accessibility and affordability story, giving millions of patents a new route for GLP-1 care and coverage. However, this is also very much a cardiology story, as it could reduce those same millions of patients’ major cardiac events by 20%, while giving cardiologists a central role in managing a drug class that’s poised to dominate the next decade.

Novo Nordisk Expands CV Pipeline with Ocedurenone Acquisition

Posted on by Jake Fishman

What do you do when a blockbuster drug drives up your revenue and market cap to unprecedented levels? If you’re Novo Nordisk, you take that capital and expand your cardiovascular drug pipeline by acquiring ocedurenone from KBP Biosciences for $1.3 billion.

  • Ocedurenone is a late-stage oral non-steroidal mineralocorticoid receptor antagonist (nsMRA) that has “best-in-class” potential for uncontrolled hypertension
  • It’s also viewed optimistically for treating other cardiovascular and kidney diseases

Ocedurenone has nine trials to support this optimism, including…

  • The BLOCK-CKD Phase 2b trial, in which ocedurenone significantly improved systolic blood pressure among patients with stage 3b/4 CKD and uncontrolled hypertension, without reports of hyperkalemia or acute kidney injury
  • The ongoing CLARION-CKD phase 3 trial, which evaluates the same patient groups and outcomes across a larger multi-site study population

Novo Nordisk expects to launch additional phase 3 trials in the coming years evaluating ocedurenone’s impact on cardiovascular and kidney diseases, as it seeks to “maximize” the drug’s “full potential.”

  • That combination of indications would position ocedurenone as a rival to Bayer’s nsMRA, Kerendia, which currently has FDA approval for kidney disease, but has shown benefits for hypertension and CVD.

The acquisition also closely aligns with Novo Nordisk’s strategic focus on leveraging its semaglutide windfall to expand to new serious chronic disease treatments (beyond its core focus on diabetes).

  • Novo Nordisk’s other recent acquisitions looked to bolster its leadership in the weight loss segment, including Danish startup Embark Biotech and Canadian biotech Inversago Pharma in August.

The Takeaway

Semaglutide has been very good to Novo Nordisk, driving a nearly 90% market cap increase in the last year, and setting the stage for 32% to 38% in 2023 revenue growth. Novo Nordisk’s semaglutide party won’t last forever, but this acquisition strategy suggests that it will have a full chronic disease drug pipeline when that day comes.

Novo Nordisk Expands Weight Loss Pipeline with Inversago Acquisition

Posted on by Jake Fishman

Novo Nordisk added to its leadership position in the white hot weight loss segment, acquiring Canadian biotech Inversago Pharma for up to $1.075 billion depending on certain development and commercial milestones.

Inversago Pharma develops therapies that block cannabinoid receptor type 1 proteins (CB1) to treat obesity, diabetes, and other metabolic disorders, although Novo Nordisk appears most interested in Inversago’s lead asset: INV-202.

  • INV-202 is an oral CB1 inverse agonist (a once-daily pill) that has shown promise for weight loss and appetite suppression in a Phase 1b trial, allowing users to shed an average of 7.7 pounds in 28 days (vs. 1 lb avg. gains in the placebo group)
  • INV-202 has also advanced to a Phase 2 trial for diabetic kidney disease, while Inversago’s other assets target metabolic and fibrotic disorders

Novo Nordisk was sure to position Inversago’s portfolio as “next-generation CB1 receptor blocker therapies,” highlighting their unique approach of targeting CB1 receptors in peripheral tissues (e.g. GI tract, kidneys, liver, pancreas, muscles, lungs).

  • That differentiation is notable given that Sanofi had to withdraw its Acomplia (rimonabant) CB1 weight loss drug in 2008 due to concerns about the psychiatric side-effects from inadvertently targeting brain tissue
  • It’s also quite different from Novo Nordisk’s injectable semaglutide (Ozempic and Wegovy), which mimics the GLP-1 hormone released in the gut in response to eating, prompting the body to produce more insulin and reducing blood sugar

The acquisition also suggests that an early-stage obesity drug startup land grab might be underway, led by the two pharma giants who are already leading the weight loss segment.

  • Inversago’s “up to” $1.075B acquisition price represents a nearly 10x premium over the $111M that it raised through its Series C round
  • Lilly acquired cardiometabolic disease biopharma startup Versanis for up to $1.92B just a few weeks ago for well above Versanis’s $70M Series A funding

The Takeaway

Semaglutide and tirzepatide made Novo Nordisk and Eli Lilly early leaders in the emerging weight loss segment, and their recent acquisitions reveal that the companies are now filling out their weight loss pipelines to ensure continued leadership.

These acquisitions have come with hefty potential premiums, but considering that GLP-1s generated $4.5B in global revenue last quarter (with minimal payor coverage) and given that the weight loss segment could be worth $100B by 2030, Novo Nordisk and Lilly clearly view these bets as justified.

Wegovy Cuts Weight and Cardiovascular Events

Posted on by Jake Fishman

The hottest medication in the world got even hotter this week after Novo Nordisk revealed that its weight loss drug Wegovy (semaglutide) also reduces major cardiac event risks by 20% – a revelation that could change how GLP-1s are used, perceived, and reimbursed.

Novo Nordisk’s double-blinded SELECT trial gave either semaglutide (2.4 mg weekly) or a placebo to 17,604 non-diabetic obese adults with cardiovascular disease (≥45yrs, mean BMI 33, 41 countries, 800 sites) in addition to standard of care. 

Over a 5-year follow up period, the semaglutide group…

  • Had a 20% lower risk of major cardiovascular events
  • Achieved reductions in cardiovascular death, heart attacks, and stroke
  • Showed that semaglutide was safe and well-tolerated, matching previous trials

Although the complete study hasn’t been released, these topline results were widely viewed as among the most significant from a preventative cardiology trial in recent memory. They also sparked a frenzy on CardioTwitter, and widespread coverage across cardiology and mainstream news sites, while driving a massive 14% surge in Novo Nordisk’s stock price in a single day. 

And for good reason. If semaglutide and other GLP-1s are proven to truly slash CV events by a fifth it could…

  • Improve the cardiovascular health of an untold number of GLP-1 users
  • Prompt the FDA to approve semaglutide for CV risk reduction
  • Pressure Medicare and commercial payors to finally cover weight loss drugs
  • Reverse critical narratives around weight loss medications
  • Solidify cardiology’s role in weight and cardiometabolic care
  • Further expand the (already massive) value of the weight loss segment

On a more scientific note, SELECT also prompted some interesting discussions regarding what’s driving semaglutide’s CV event reductions (e.g. directly from weight loss, cardiometabolic improvements, vascular improvements, all of the above). Further understanding of these mechanisms might lead to new CVD treatments.

The Takeaway

Although many cardiologists weren’t surprised that GLP-1 users would also have better cardiovascular outcomes, the SELECT trial’s 20% MACE reductions seemed to leave nearly everyone astounded. 

Considering that there were 135,000 new semaglutide prescriptions in the United States in May 2023 (without payor coverage or CVD evidence), GLP-1s’ long term population health impact might prove to be more astounding than any of us imagined.

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