More background on NVO

 NOVO NORDISK FY24

Note the scepticism and uncertainty around the latest trial results.

Call summary 

Lars Fruergaard Jorgensen -- President and Chief Executive Officer

In 2024, we delivered 26% sales growth and 26% operating profit growth.

Starting with our focus on purpose and sustainability, we are now serving more than 45 million patients with our diabetes and obesity treatments. This is an increase of almost 4 million patients compared to last year and reflects our continued capacity expansion efforts.

In R&D, we had several exciting obesity readouts this quarter, such as CagriSema, semaglutide 7.2 milligrams, and amycretin. These results reinforce our strategic aspiration of developing superior treatment solutions for people living with obesity. For CagriSema, we remain confident in its potent biology and look forward to further exploring its potential and to making it available to patients.

Camilla Sylvest -- Executive Vice President, Commercial Strategy and Corporate Affairs

In 2024, our total sales increased by 26%. The sales growth was driven by both operating units with North America operations growing 30% and international operations growing 19%. In the U.S., sales growth was positively impacted by gross-to-net sales adjustments.

Our GLP-1 sales in diabetes increased by 22%, driven by North America operations growing 23% and international operations growing 18%. Insulin sales increased by 17%, driven by North America operations growing 52%, positively impacted by gross-to-net sales adjustments and international operations growing 6%. Obesity care sales increased 57%, driven by North America operations growing 45% and international operations growing 107%. In both geographies, growth was driven by Wegovy, partly offset by declining Saxenda sales as the obesity care market is moving toward once weekly treatments.

Rare disease sales increased by 9%, driven by a 20% increase in North America operations, and the rare disease sales in international operations remained unchanged compared to last year.

Novo Nordisk is the global GLP-1 volume market leader, serving nearly two-thirds of all patients on GLP-1 treatments across diabetes and obesity. Our ongoing scaling efforts have supported an almost tripling of GLP-1 patient reach over the last three years. In December 2024, we announced that the acquisition of the Catalent sites from Nova Holdings was completed. This transaction supports our ongoing scaling efforts and will expand Novo Nordisk global fill and finish footprint from 11 to 14 sites. We still expect the three sites to gradually increase market supply beyond our preexisting CMO contracts to the market from 26 and allow us to reach significantly more patients in the years to come.

Within diabetes care, sales growth was 20%, driven by our GLP-1 portfolio and insulins. We sustained our diabetes value market share leadership with an unchanged market share of 33.7% compared to last year.

This remains above our strategic aspiration of reaching one-third of the global diabetes value market in 2025. In international operations, diabetes care sales increased by 12% in 2024, which was mainly driven by GLP-1 diabetes care sales growing 18%. Novo Nordisk remains the market leader in international operations with the GLP-1 diabetes value market share of almost 64%.

David Moore -- Executive Vice President, US Operations and Global Business Development

Sales of GLP-1 diabetes care products in the U.S. increased by 24%.

The sales increase was mainly driven by the continued uptake of Ozempic and the GLP-1 class growth. Novo Nordisk remains the market leader in the U.S. with more than 52% market share measured by total monthly prescriptions.

Wegovy sales increased by 86% globally, driven by a 59% growth in North America operations, and Wegovy sales in international operations have reached more than DKK 11 billion. The global total branded obesity market more than doubled with a growth rate of 119%. In the U.S., the Wegovy sales growth was driven by increased volumes, partially countered by lower realized prices in the U.S. The positive volume development was also reflected in the Wegovy prescription trends in the U.S., which currently is around 200,000 weekly prescriptions. That's compared to around 100,000 weekly prescriptions in January 2024. We have reached broad formulary access for Wegovy in the U.S. and continue to work on expanding it further. Currently, Wegovy has coverage for around 55 million people living with obesity in the United States. In international operations, Wegovy has now been launched in more than 15 countries, underlining our commitment to reaching more patients.

Our rare disease sales increased by 9%. This was driven by sales in North America operations of 20%, while sales in international operations were unchanged. Sales of rare endocrine disorder products increased by 31%, driven by launches of Sogroya and increased Norditropin supply, as well as a positive impact from gross-to-net sales adjustments in the U.S. Rare blood disorders sales increased by 3%, driven by an increase in hemophilia B sales.

Martin Holst Lange -- Executive Vice President, Development

In December, Novo Nordisk released the headline results from the first pivotal trial with CagriSema REDEFINE 1 in people living with obesity or overweight.

Based on the CagriSema weight loss data observed in Phase 1 and 2 trials, we incorporated a flexible protocol in REDEFINE 1. The protocol followed a 16-week titration schedule and permitted dose modifications based on tolerability or concerns about excessive weight loss throughout the trial. This was done to balance efficacy, tolerability, and trial dropout. REDEFINE 1 was a 68-week efficacy and safety trial with 3,417 people enrolled. Previous trials and our modeling indicated that CagriSema could provide a potential weight loss of approximately 25%, while the 25% weight loss was not observed in REDEFINE 1, we are encouraged by the weight loss profile of CagriSema which stands out as one of the most substantial weight reductions observed in a clinical Phase 3a trial.

In the REDEFINE 1 trial, the extent of dose modification prompted us to conduct a more in-depth analysis of people receiving the highest dose at 68 weeks, followed by an analysis of people on lower doses at 68 weeks. The first subgroup comprised 57% of the total population and consisted of people in the trial who ended on the highest 2.4 milligrams dose of CagriSema at 68 weeks. The second group accounted for 29% of the population consisted of those who were at lower doses of CagriSema at 68 weeks.

This suggests that additional weight loss could be achieved with a trial of longer duration.

Overall, CagriSema demonstrates a potent treatment response resulting in a superior weight loss efficacy compared to semaglutide. Furthermore, the REDEFINE 1 data indicate that a patient-centric and individualized treatment regimen which take the initial dose escalation -- dose reescalation and trial duration into account could potentially enhance efficacy of CagriSema while maintaining a favorable safety profile. While it may appear counterintuitive that lower doses of CagriSema leads to more substantial weight loss.

Based on the insights from REDEFINE 1 and the reflection I've just shared with you on the data will further explore Cagrisema potential in a new Phase 3 trial, REDEFINE 11. The trial will have a longer trial duration and focus on dose escalation and reescalation.  CagriSema. We are currently anticipating the results of REDEFINE 2 in the first quarter of 2025.

The REDEFINE 11 trial will be initiated in the first half of 2025 and we now expect to submit CagriSema in the first quarter of 2026. The adjusted timelines are not related to the redefined development program but driven by supply chain reticentness when launching into a large and rapidly expanding market of obesity.

We are very encouraged by the results for subcutaneous amycretin for people living with overweight obesity. And based on the results, we are now planning for further clinical development of amycretin in people with overweight obesity.  Overall, we have a competitive portfolio in obesity underlined by the recent readouts from CagriSema, semaglutide 7.3 milligrams, and subcutaneous amycretin. Our strategic ambitions remains to build a portfolio of superior treatment options in obesity and a focus on efficacy, safety, and scalability, be it injectable or oral.

Karsten Munk Knudsen -- Executive Vice President, Chief Financial Officer

In 2024, our sales grew by 25% in Danish kroner and by 26% at constant exchange rates, driven by both operating units. In the U.S., sales growth was positively impacted by gross-to-net sales adjustments.

The gross margin increased to 84.7%, compared to 84.6% in 2023. The increase is mainly driven by a positive price impact due to growth to net sales adjustments in the U.S. and the positive product mix. This is partially countered by costs related to ongoing capacity expansions.

Operating profit is positively impacted by gross-to-net sales adjustments in the U.S. and negatively impacted by impairment losses.

Guidance

Consequently, following the further step-up in capex, Novo Nordisk is not initiating a new share buyback program at this point in time. We continued the growth momentum in 2025 and expect the sales growth to be between 16% and 24% at constant exchange rates. This is based on several assumptions as described in the company announcements. The guidance reflects expansion expectations for sales growth in both North America operations and international operations. the sales growth is expected to be mainly driven by volume growth of GLP-1-based treatment for obesity and diabetes care, also reflecting our continued scaling of our supply chain. Our reported sales are expected to be 3 percentage points higher compared to constant exchange rates and operating profit is expected to be 5 percentage points higher compared to constant exchange rates.

We expect that the operating profit will grow between 19% and 27% at constant exchange rates. This primarily reflects the sales growth outlook and continued investments in current and future growth drivers within research, development, and commercial. And negative mid-single-digit operating profit growth impact related to the acquisition of the three Catalent manufacturing sites is also included in the guidance. For 2025, we expect net financial items to amount to a loss of around DKK 9 billion.

This mainly reflects losses on currencies, primarily the U.S. dollar, and increased interest expenses related to funding of the Catalent site transaction as this acquistition was mainly debt financed.

Capex is expected to be around DKK 65 billion in 2025, reflecting expansion of the supply chain. In the coming years, capex to sales ratio is still expected to be in the low double digits. The free cash flow is expected to be DKK 75 million to DKK 85 billion, reflecting the sales growth, a favorable impact from rebates in the U.S. countered by increased investments in manufacturing facilities.

Questions & Answers:

Wegovy meeting demand in the US

I think it's important to remember that the total market for anti-obesity medicines grew in the U.S. last year by 160%. And so the story continues to be about market expansion for obesity. And for our brand, Wegovy, recall, we started last year with around 100,000 prescriptions and ended with over 200,000 prescriptions. And so the scaling efforts are recognized and that's being pulled through in the market. At the beginning of the year, and this is normal, there are movements in benefit plans and patients changing in terms of their co-pays and co-insurance.

It's important to remember, we're treating 1.2 million patients with Wegovy today, and we have access of 55 million people living with obesity in the U.S. Driving new prescriptions is, of course, our focus. We are shipping more of the starter doses as we speak. Those started doses are making their way through the supply chain from the wholesaler to a retailer, which is also new for us to have this amount of new starter doses.

CariSema Trial results REDEFINE 4

REDEFINE 4, as you rightly mentioned, this had trial CagriSema versus semaglutide. The first statistical testing will be non-inferiority and based on what we've seen with REDEFINE 1, there's a good assumption that will come out with non-inferiority established. Second test for superiority. And again, I think it's too early to speculate, but we will see the data when we will see them, but that is test number two.

Hi there. Thank you for taking my questions. It's Harry Sephton from UBS. I'd like to start with the REDEFINE 1 results, and can we address this difference between the weight loss profile that doesn't show a typical dose response? You talked about the fact that fewer patients finished at the higher dose in the initial results as a potential explanation to the weaker weight loss versus your modeling, the data you've shown today somewhat contradicts this.

So what have you seen to explain this discrepancy? Is it a speed of titration issue? Or are there other factors you can help explain this? And what read across can you take from these data for the imminent REDEFINE 2 data? My second question is following the amycretin subcu data. How do you see the positioning of this product versus CagriSema in the future? Do we need incremental efficacy from here? Or does the benefit from amycretin more come from scalability and the flexibility of both the injectable and oral formulations? And what is the timing for the initiation of your Phase 3 program for amycretin? Thank you.

Jacob Martin Wiborg Rode -- Head of Investor Relations

Thank you, Harry, for those two questions. On the first one, in terms of REDEFINE 1 data, we'll turn it to you, Martin.

REDEFINE 1 results

So first of all, I think it's important to call out, we don't really see discrepancies. We see a picture emerging that we've seen to an extent in the step certainly in the step-up study programs, and we see that also now in REDEFINE 1. We see a group of people who titrate with very strong safety and tolerability to the fullest dose. They have a very substantial weight loss. And specifically in REDEFINE 1, we see the potential for even further weight loss with longer treatment duration. Then we see some early responders who clearly lose weight faster than the other group. They also appear to have the potential to lose more than the other group. And what we can see from this is basically that on average, that group which is bigger than what we've normally seen in our trials, loses a mean of 25.2 percentage point at the end of trial, approaching a BMI that would indicate nonobesity. That actually then plays into a dynamic because these patients have slightly more gastrointestinal side effects, they also -- some of them expressed concerns about the speed of weight loss. And therefore, they start to titrate a little bit down. That, again, is a big potential because they can actually lose more weight. It's to your point, allowing them to do individual dose titration. -- titrate a little bit slower and then coming up to higher doses, balancing the speed of their weight loss and the gastrointestinal side effects. Obviously, this population also seems to be benefiting from an even -- or could be benefiting from an even longer trial duration. And that basically means we see two distinct groups, one being what we call early or high responders. But both groups actually show more weight loss potential. We can utilize that in the future programs for Cagrisema, specifically starting with REDEFINE 11. But we can certainly also use those data when we designed the amycretin program using the same biology.

Addressing the market

There's no doubt that with the size of the obesity market, it will be a key strength to have a broad portfolio of products. We believe we have a very strong portfolio that enables us to work with optionality, optionality in terms of different patient segments and different markets to address the big unmet need that there is. Remember, there are very few percentage points of the total population that is currently being treated. And I think historically, we've talked about sort of the people with obesity as one group. But as we expand our portfolio, we will be able to target different needs of different segments, as well as different geographies.

Scaling Production

So actually, we have grown faster in terms of serving more patients over the last 12 months based on IQVIA -- then I'd say as a forward-looking statement in terms of our scaling into 2025. With the guidance we have and the size of the base we have, you can say, a sales growth in, say, a midpoint of 20%, then you apply rebate enhancement and few mix impacts and share of the total portfolio, then then you get to a scaling of GLP-1 franchise in terms of patients served nicely in excess of 30% into this year. So I think we are very competitive in terms of scaling.

Products in Obesity 25ml v 50ml

High-level value proposition back to what we talked about before. It is likely that there will be an all segments in obesity as there has been actually also before, but due to tolerability issues, this has been quite small. Now we have product that is moving in terms of clinical trials and efficacy with a 16% weight loss or semaglutide 25 milligram. And of course, that gives us an opportunity to launch this in selected markets.

And with that, we will, of course, benefit from the benefits of semaglutide in general, and this gives us optionality to address an oral more specifically. So that's part of our plans and our order portfolio.

 

 

Marketing confusing results?

Yeah. So agree, of course, with the results we have seen, we are very confident in the product. We are very confident in our portfolio, and it's the optionality that we are working with on how to target specific segments and specific geographies. I think it's a little bit premature for us to reveal our full commercial approach as to how we are utilizing the benefits of these different options that we have in our pipeline, but it is the sum of the pipeline that we just talked to that will really enable us to address more and more people living with obesity. And why you will also see us addressing different types of products with different optionalities as we just discussed all now CagriSema, amycretin, and of course, also higher-dose Wegovy. This is all part of our opportunity to play in obesity.

Swing factors in Guidance

I would call out three main ones, one being supply as we've seen in prior years and more supply can make us reach more patients and and more markets. And of course, negative supply fluctuations would impact the other way. Number two is competition and magnitude of competition. of course, we do not have forward-looking visibility to we see what's in the market today. So it's based on our current read of the markets. And then the third factor is gross-to-net adjustments where we've seen some sizable gross-to-net adjustments in the U.S. over the past few years, reflecting a 69% spread between gross and net sales in the U.S. and that swing factor can also both be positive and negative. So that would be the main three factors.

Result inconsistencies

 We have seen a difference in how patients respond. That has been based on, say, lower potency products. So we saw a similar -- when we developed Wegovy but with less, say, spread, so to say. And in our view, we have to relate to that when you develop highly potent biologies like what we see with CagriSema, these differences will be amplified. So the fact that patients are different and respond in a different way means that we'll see increasingly as we move up and develop highly efficacy products, you will see this difference in response. And in terms of use in the market also to the prior question, I think it's perhaps less confusing for physicians than we believe because they actually use to patients responding quite differently on treatment. And that goes for obesity, but it also goes for any, say, chronic disease that patients respond differently to medicines. So physicians are used to a more patient-centric treatment regime. And I think what really matters here is that we have a highly potent biology that kind of does the job.

So in the group where patients did not titrate to full dose at end of trial, the mean dose at week 20 was around 1.5 milligrams, indicating that very few actually opted to try the full 2.4 milligram dose. This is more to be seen as a group of fast and high response. And therefore, with the weight loss that they accrued, which was then also faster than the other group, they started to slow down to balance the speed of their weight loss, their gastrointestinal side effects, but also the fact that they were approaching a level below the definition of obesity. And therefore, again, it speaks to the very powerful biology that we see, but also the need to individualize treatment. And again, I'll just remind you, this is the trial at a population level where we've seen very few gastrointestinal side effects at the level of Wegovy. And therefore, that is not the key driver of how patients choose to titrate. Patients know how to do this together with their physicians.

But when you get into, say, the next-generation products, where you amplify the weight loss, you tease out the difference between different patients who we are still trying to look into the omics and figure out what defines the difference. And we have a lot of data. So we can start actually finding ideas about who will respond in certain ways and from a speed of weight loss, etc. So that -- then we're into the topic of, say, quality of weight loss. And I think in the early days of obesity, we have all been obsessed with the percentage over time. And I think that's a problematic ratio because if you have lived with obesity, a good part of your life and suddenly, you lose, say 25%, in some even more per cent weight loss in a matter of, say, half year to a year, that's a very, very dramatic, say, change in your life and not necessarily what anyone would like. And then, of course, we have all the comorbidities. And increasingly, I think with the establishment of CV benefits, liver benefits, etc., it also becomes a matter of, say, the health outcome improvements you have. So in this, say, opportunity space, I think it's important to be able to address those opportunities with different types of agents, to cater for these differences. Short term, as I mentioned before, I think patients together with the physician are quite comfortable managing this journey. And I think we are perhaps struggling a bit in doing the perfect segmentation of what this market will look like. But I think we can look into all the data we have and find ways to also more targeted direct specific products to certain subsegments. So I think this is another example of the fact that we're in the early days of understanding obesity, and how patients are different. And I think it's all opportunity for us with the breadth of the portfolio we have and all the data we have. So yes, the percentage of weight loss matters what quality of weight loss and the benefit of comorbidities, etc., etc., also matters. And it's a net total equation that I think we have a really exciting opportunity for continuous leadership in the space.

What matters in building a market

We must reiterate that -- it's our belief that building a sustainable obesity market for the long term is through market access and having patients that have a reasonable co-pay and access to the medicine. I'm happy to say for 2025 that we have maintained our broad access for Wegovy, covering 55 million people with obesity.

There were no major changes with opt-ins and opt-outs. It's important to note that these patients have Wegovy available at a low out-of-pocket cost, more than 80% of them paying less than $25 for a prescription. And this is also, in addition, we have now more than 20 states that also cover Wegovy through Medicaid.

Impact of Compounding

Our latest market intelligence does tell us and show us that it is having an impact, and it is growing faster than we had anticipated. I want to remind everyone that we do not supply compounding, and we have significant actions in place to curtail this. Our focus is on patient safety and educating patients and providers that this is not sema and also to work with the regulators to curtail compounding as well. As you mentioned, we are still listed on the drug shortage list. We are in active dialogue with FDA. It is ongoing. Of course, as we increase the resilience in our supply that has an impact on our ability to get off the drug shortage list, and we are focused on doing that as fast as possible as we believe this will help our further actions to curtail compounding in the future.

Pricing in IRA/CMS

As expected, semaglutide-containing products, Ozempic, Rybelsus, Sema, Wegovy. They are selected for the second round of CMS negotiations. It's too early to speculate on the potential impact. As we've stated in the past, we oppose government price setting like we have from the beginning. The process, though, is as follows: the negotiations will end at the beginning of November. The maximum fair price will be published by the end of November, and it will be effective on the 1st of January 2027. And just for background, the rough U.S. channel mix across our portfolio is about 50%, commercial; 30%, Medicare; 10%, Medicaid; and 10%, other.

Amycretin

So as you know, we have generated the data on the oral version of amycretin. They are very consistent with the data that we see with the subcutaneous version of amycretin in patients with obesity. We have an ongoing Phase 2 trial in patients with type 2 diabetes. Our current assessment is that we live up to the spirit of the FDA draft guidance.

It's early days. And obviously, what we can say at this point in time is we are working with two powerful biologies. They appear to have similar efficacy, but also safety and tolerability potential. And obviously, that also means that we have to think about the power of the combination biology into our amycretin development program to accrue the full potential, both in terms of weight loss, but also safety and tolerability and potentially comorbidities when we do develop amycretin and CagriSema moving forward.

Loss of exclusivity

So in terms of whether we have changed anything in our view toward loss of exclusivity, I would say we have not. What we have learned now is, of course, that little bit more clarity on different segments. We talked about individual life treatment. We learn more about how each product works, but it only gives rise to us getting more information about how we are going to position this portfolio of opportunities that we have. So the short answer is no, and we also continue to, of course, build on the semaglutide franchise. You just saw the new indications that we got.

Jacob Martin Wiborg Rode -- Head of Investor Relations

Thank you, Martin, and also thank you to you, Michael. Now that concludes the Q&A session. Thank you for participating and feel free to contact investor relations regarding any follow-up questions that you may have. Before we fully close the call, I would like to hand over the word to you, Lars, for final remarks.

 

Here's a comprehensive analysis of the obesity market and key players:

 

The Global Obesity Market: A Transformative Era

 

The obesity treatment market is undergoing a revolutionary transformation driven by the emergence of highly effective GLP-1 receptor agonists. What was once a relatively small market dominated by lifestyle interventions and marginally effective medications has evolved into what analysts project could become a $100+ billion market by 2030.

 

Market Leaders and Their Products

Novo Nordisk

Currently leading the market with two key products:

- Wegovy (semaglutide): First FDA-approved GLP-1 for obesity in 2021

- Saxenda (liraglutide): Earlier generation product

Market position: First-mover advantage in obesity-specific GLP-1s has given Novo Nordisk a dominant position, though manufacturing constraints have limited potential market share.

Eli Lilly

Emerged as a strong competitor with:

- Zepbound (tirzepatide): Recently approved for obesity, showing superior weight loss results in trials

- Mounjaro (tirzepatide): Same molecule as Zepbound, approved for diabetes

Market position: Potentially gaining significant share due to superior efficacy data and increasing manufacturing capacity.

Viking Therapeutics

Emerging player with:

- VK2735: Dual GIP/GLP-1 receptor agonist in development

- Early trial results showing promising efficacy

Market position: Still in clinical development phase but showing potential to compete in this growing market.

 

Market Growth Projections

 

Overall Market:

- Current size: Approximately $10-15 billion (2024)

- Projected growth: Expected to reach $100-150 billion by 2030 (47% cagr)

- Key growth drivers: Increasing obesity rates, improved insurance coverage, growing acceptance of medical intervention

 

Company-Specific Projections:

 

Novo Nordisk:

- Current obesity revenue: Approximately $3-4 billion

- Expected growth: 20-25% annual growth through 2025

- Constraints: Manufacturing capacity limitations

- Opportunities: Label expansion, new formulations

 

Eli Lilly:

- Current obesity revenue: Ramping up with the recent Zepbound launch

- Expected growth: 30-35% annual growth potential

- Advantages: Superior efficacy data

- Focus: Expanding manufacturing capacity

 

Viking Therapeutics:

- Current revenue: Pre-commercial stage

- Potential: Could capture meaningful market share post-2025 if development successful

- Key differentiator: Potential for competitive efficacy profile

 

Market Dynamics and Future Outlook

 

The obesity market is expected to support multiple successful players due to:

1. Large patient population (>650 million people globally with obesity)

2. Current low penetration rates (<1% of eligible patients treated)

3. Growing acceptance of medical treatment

4. Improving insurance coverage

5. Potential for combination therapies

 

Challenges and Considerations:

 

1. Manufacturing Capacity

- Both Novo Nordisk and Eli Lilly are investing heavily in manufacturing expansion

- Supply constraints likely to persist through 2025

 

2. Pricing and Access

- Current annual cost: $10,000-15,000 per patient

- Insurance coverage improving but still variable

- Potential political pressure on pricing

 

3. Competition

- Additional companies entering development space

- Potential for oral formulations

- Future biosimilar competition

 

4. Market Evolution

- Potential for combination therapies

- Development of improved delivery methods

- Integration with digital health solutions

 

The obesity market represents one of the largest opportunities in pharmaceuticals, with potential for sustained growth over the next decade. While Novo Nordisk and Eli Lilly currently dominate the space, the market size could support multiple successful players, including emerging companies like Viking Therapeutics. The key to success will likely be a combination of manufacturing capability, clinical differentiation, and effective commercialization strategies.

 

This analysis is based on current information and projections may change based on clinical trial results, regulatory decisions, and market dynamics. Specific revenue projections and market share estimates should be verified against latest company reports and analyst forecasts.

Combination therapies in the obesity/diabetes space refer to using multiple medications together to potentially achieve better results than single drugs alone. Here's a breakdown:

 

Current Development Areas:

 

1. GLP-1 + Other Incretin-Based Drugs

- Combining GLP-1 receptor agonists with GIP or glucagon receptor agonists

- Example: Tirzepatide (Mounjaro/Zepbound) already combines GLP-1 and GIP effects

- Several companies developing triple receptor agonists (GLP-1/GIP/Glucagon)

 

2. GLP-1 + Amylin Analogues

- Novo Nordisk developing CagriSema (combines Wegovy with amylin analogue)

- Potential for greater weight loss than GLP-1 alone

- Different mechanism of action could complement GLP-1 effects

 

3. GLP-1 + Small Molecules

- Companies exploring combinations with:

  - Appetite suppressants

  - Metabolic modulators

  - Novel target compounds

 

Potential Benefits:

- Greater weight loss than monotherapy

- Different mechanisms addressing multiple pathways

- Potential for better maintenance of weight loss

- Possible reduction in side effects through lower doses

 

Challenges:

- Increased complexity in manufacturing

- Higher cost of therapy

- More complex regulatory pathway

- Potential for increased side effects

- Drug-drug interactions

 

Companies Active in Combination Development:

- Novo Nordisk: Leading with CagriSema development

- Eli Lilly: Exploring various combinations

- Structure Therapeutics: Working on oral combinations

- Several biotechs exploring novel combinations

 

This is an active area of research and development that could represent the next wave of innovation in obesity treatment after the current generation of GLP-1 based therapies.

 

Semaglutide vs. Tirzepatide: Comprehensive Comparison

Efficacy

Weight Loss

• Tirzepatide (Zepbound/Mounjaro): Superior weight loss profile
• Phase 3 SURMOUNT-1 trial: 15-20.9% weight loss at highest dose (15mg)
• Average weight loss: ~22.5% at 72 weeks (15mg dose)
• Semaglutide (Wegovy/Ozempic): Strong but less pronounced effect
• Phase 3 STEP trials: 15-17% weight loss at highest dose (2.4mg)
• Average weight loss: ~15% at 68 weeks (2.4mg dose)

Glycemic Control (for diabetes)

• Tirzepatide: Superior A1C reduction
• A1C reduction: 1.8-2.1% (15mg dose)
• Higher percentage of patients reaching A1C targets
• Semaglutide: Effective but slightly less potent
• A1C reduction: 1.4-1.8% (1mg dose in diabetes)
• Still achieves significant improvements over standard of care

Side Effects

Common Side Effects (both drugs)

• Nausea, vomiting, diarrhea
• Constipation
• Decreased appetite

Differentiating Factors

• Tirzepatide: Possibly higher rates of GI side effects in clinical trials
• Discontinuation rates: 5-7% due to adverse events
• May have slightly higher incidence of nausea initially
• Semaglutide: Established safety profile with more real-world data
• Discontinuation rates: 4-7% due to adverse events
• More long-term safety data available

Cost

• Tirzepatide:
• List price: ~$1,000-1,100/month
• Similar insurance coverage patterns emerging
• Semaglutide:
• List price: ~$1,300-1,400/month
• More established insurance coverage
• Greater availability of patient assistance programs

Commercial Factors

Novo Nordisk (Semaglutide) Advantages

• First-mover advantage in obesity
• Established brand recognition
• Longer market presence
• More extensive formulary placement
• Recently approved lower doses for maintenance

Eli Lilly (Tirzepatide) Advantages

• Superior efficacy data
• Dual mechanism of action (GLP-1 and GIP)
• Potentially better benefit-risk profile
• Ramping up manufacturing capacity
• More recent clinical data

Market Dynamics

Supply Constraints

• Semaglutide: Significant supply limitations through 2023-2024
• Tirzepatide: Initially limited but capacity expanding rapidly

Formulations

• Semaglutide: Available in both injectable (Wegovy/Ozempic) and oral (Rybelsus) forms
• Tirzepatide: Currently injectable only, oral formulation in development

Pipeline

• Semaglutide: Combination with amylin analogue (CagriSema) showing enhanced efficacy
• Tirzepatide: Various combinations and formulations in development

Key Differentiators for Sales Success

1. Manufacturing capacity: Currently a major limiting factor for both
2. Insurance coverage expansion: Critical for widespread adoption
3. Patient persistence: Adherence rates will impact lifetime value
4. Provider familiarity: Prescriber comfort with respective products
5. Marketing execution: DTC advertising and provider education

The superior efficacy profile of tirzepatide gives it a potential advantage, but Novo Nordisk's first-mover position with semaglutide provides established market presence. The winner in this market will likely be determined by a combination of manufacturing capability, marketing execution, and insurance coverage expansion rather than just clinical profile alone.