Report: Semaglutide and the Way Forward - Price Erosion, impact of GLP-1 agonist
Report
Semaglutide and the Way Forward
Price Erosion, impact of GLP-1 agonist
Table of Contents
Various antidiabetic molecules are available, affecting different organs with their MOA. 5
What is so special about semaglutide? 5
Different Semaglutide Brands 5
When could patients avail of low-cost injectable semaglutide? 7
Patent and Regulatory Scenario: 7
LoE dates for injectable dosage forms: 8
How safe is Semaglutide today? 10
Price erosion calculations for Semaglutide: 10
Case 1: 50% erosion, the situation would be as follows: 11
Case 2: 70% erosion, the situation would be as follows: 11
The potential impact of generic Semaglutide launch on other GLPs 11
Generic launches in key countries in APAC, MENA, and Asia 12
Technical and Commercial Information 12
Possibility of price erosion post-low-cost Semaglutide 12
Generic launches in critical countries in APAC, MENA, and Asia 12
Technical and Commercial Information 13
Possibility of price erosion post-low-cost Semaglutide 13
Generic launches in critical countries in APAC, MENA, and Asia 13
Technical and Commercial Information 13
Possibility of price erosion post-low-cost Semaglutide 13
Generic launches in critical countries in APAC, MENA, and Asia 14
Technical and Commercial Information 14
Possibility of price erosion post-low-cost Semaglutide 14
Executive summary
Generic Semaglutide entries will be very eventful. The brand will do everything to deter generics from launching.
SRM generic entries will be in 2031.
Semaglutide prices may drop to at least 50% in LRMs.
Total Semaglutide sales in China and RoW after patent expiration in 2026 could be USD 1.8 bn to USD 3 bn.
Liraglutide and Dulaglutide prices will be impacted due to low-priced Semaglutide generic launches.
According to their investor presentation, Novo Nordisk is clearly in the leading position in diabetic and obesity care. Here. The report's objective is to understand the impact of generic Semaglutide.
PART I
Various antidiabetic molecules are available, affecting different organs with their MOA.
Metformin increases glucose uptake by targeting liver and skeletal muscles to reduce gluconeogenesis
Thiazolidinediones (TZDs) act as insulin sensitizers in skeletal muscle, adipose tissue and the liver by binding to peroxisome proliferator-activated receptors (PPARs).
Sulfonylurea and Meglitinides increase insulin secretion in the pancreas by binding sulfonylurea receptors (SURs) on the surface of beta cells and causing potassium ion channel inhibition.
Dipeptidyl-peptidase IV (DPP-4) inhibitors increase the levels of active incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which inhibit the release of glucagon and increase insulin secretion.
Sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduce renal glucose reabsorption, independent of insulin secretion.
GLP-1 receptor (GLP-1R) agonists target the pancreas to increase insulin secretion, reduce glucagon production and reduce gastric emptying.
Weight-loss
It is reported that a 2.4 mg once-a-week SC dose of semaglutide caused 16.1% average weight loss from baseline. Weight loss peaks at week 60, and reduction was maintained for 104 weeks. More details about the study could be found here
What is so special about semaglutide?
Different Semaglutide Brands
Ozempic (injection) is FDA-approved to reduce blood sugar levels in adults with type 2 diabetes. It’s also approved to lower the risk of serious cardiac events such as stroke, heart attack and death in individuals with diabetes and heart disease. Weekly doses range from 0.25 milligrams to 2 milligrams. Clinically recommended for patients with T2DM with a BMI more than 27, comfortable taking an SC injection once a week.
Wegovy (injection) is FDA-approved for use in adults and children over the age of 12 who have obesity or who have weight-related health issues such as high cholesterol, type 2 diabetes or high blood pressure. It’s taken weekly in doses ranging from 0.25 milligrams to 2.4 milligrams. Clinically recommended for patients who are comfortable with a weekly self-injection and have a BMI of 30 (with or without weight-related health complications) or a BMI of at least 27 with at least one weight-related health complication (like high cholesterol or hypertension). It should be used alongside a reduced-calorie diet and increased physical activity.
Ozempic and Wegovy are different brand names for semaglutide formulations. The difference is that Wegovy is approved to manage those who are obese. Ozempic is approved to lower blood sugar with type 2 diabetes (T2D)
Rybesus (tablet) is FDA-approved to lower blood sugar levels in adults diagnosed with type 2 diabetes. It’s taken daily in doses ranging from 3 milligrams to 14 milligrams. Clinically recommended for patients with T2DM with BMI more than 27.
SNAC Technology
SNAC (Sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate) technology is used in oral semaglutide.
It has been used to enhance the absorption of semaglutide and protect it from degradation by gastric enzymes when administered orally, leading to its approval as the first oral glucagon-like peptide 1 receptor agonist for treating type 2 diabetes.
Novo Nordisk's patent families WO2013139694 and WO2014177683A1 protect this technology. Though these families are being litigated in many countries, and the outcome of the litigations is awaited, they will expire in 2033/2034.
The oral dosage of semaglutide will be very interesting for the patients. However, this paper does not emphasise oral semaglutide much because generic oral semaglutide formulations are far away.
Efficacy:
The SELECT trial is the largest study of GLP-1 receptor agonists to date. The details are available here.
Clinician’s perspective:
In addition to glycaemic control, semaglutide has the added advantage of reducing weight. Studies have suggested up to 16% weight reduction, which gives this molecule a distinct advantage.
The SELECT trial suggests the cardiovascular benefits to obese or overweight patients. Considering the chronic nature of the disease, the injectable route of administration, especially for type 2 DM, can be restrictive.
Semaglutide scores over other GLP-1s due to the availability of its oral formulations. The cost of therapy will play an important role. Hence, already-controlled diabetics may not be given unless weight reduction is clinically warranted, such as patients at risk of fatty liver or women with PCOS.
A more economical brand, if available, may expand its use even in controlled diabetics for offering weight reduction benefits.
Tirzepatide, the most recent T2DM medication, is a twincretin (a synthetic drug that helps control blood sugar levels and reduce weight ) with a dual action: it is an agonist of the GIP and an agonist of GLP-1 receptors. It is effective in the treatment of NASH, T2DM, and overweight and obese patients independent of their diabetes status.
The SURPASS group of trials has studied the effects of Tirzepatide 5.10 or 15mg administered subcutaneously once a week. Tirzepatide has demonstrated the most astounding weight loss results and has outperformed all other comparable drugs, including semaglutide.
Despite this, more research is needed to determine the long-term efficacy & safety of these agents.
Owing to their substantial effect on weight, semaglutide and tripeptide are likely recommended by non-medicos for weight reduction. Hollywood celebrities have openly talked about taking these medicines for weight loss. This may boost sales initially, but it may increase the risk of reporting serious adverse events if used in non-indicated patients.
Our view:
Semaglutide and Tirzepatide will capture most of the GLP-1 market this decade. There is no competition soon.
When could patients avail of low-cost injectable semaglutide?
Patent and Regulatory Scenario:
It is a very complex patent landscape.
However, WO20060975371 should be considered a basic patent family. Expiration of equivalents of this patent family.
Novo Nordisk has filed more than 20 patent families in several jurisdictions. Generic players must address these secondary patent families before the launch on Day-1. This will be very challenging as Novo Nordisk’s lawyers will try to keep generics away.
The very general IP and regulatory scenario of Semaglutide is as follows.
NA: Data Exclusivity provisions are not available by law.
Many of these patents are being litigated.
In the EU, there is an 8+2(+1) formula for data and marketing exclusivity, which means that the originator’s data is protected for 8 years, and originators have marketing exclusivity for a maximum of 11 years from the first marketing approval in the EU. Exclusivity period: 8+2(+1)
LoE dates for injectable dosage forms:
Many LRMs and countries, like CA and CN, will have a LoE date in March 2026.
In Europe, LoE would be in March 2031
In the US, LoE would be December 2030.
This is based on the expiration of the basic patent and data exclusivity. This will change as soon as generic companies prepare to launch. One can see a lot of litigations in these countries, and Novo will try to extend the generic launch dates.
Our view:
Generic entries will be in March 2026 in countries like China, India, and Canada, and Novo will make great efforts to deter the generic competition. Too many litigations will start in Q1/Q2 2026, and new generic launch dates will be decided after settlements between generic companies and Novo.
Price erosion:
There are several reports on price erosion post-patent expirations. A summary of some of those is below.
US-Market
The IQVIA report, published in 2019, deals with the price erosion of complex generics. Semaglutide could be considered a complex generic. The report explains how prices of complex generics would go down with the increase in the number of players in the market. It is a study specific to the US market2.
Europe-Markets
In Europe, there is a price approval process. However, we found no price erosion study specific to a complex generic. One report from IQVIA states that prices of medicines following patent expiry dropped 61% in 14 European countries due to market access to generic drugs3.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1200641/full
India
One study in India deals with price erosion after patent expiration. The following are some examples from the report, prepared in 2018 by Sudeep Chaudhari, a retired professor at the Indian Institute of Management Calcutta4.
In March 2016, the costliest medicine in India was Cabazitexal. It was protected then by a patent and Emcure if the marketing arrangement with Sanofi was the sole seller, charging a price of Rs. 3,30,000 for 60MG/1 ML injection. The price was reduced to Rs 32359 when the first generic product was introduced in June 2016. After that, as additional generic companies entered the market, the price fell to Rs 32359 in October 2016, Rs 19947 in March 2017, and Rs 18947 in August 2017.
Similarly, the price erosion that has taken place in Luliconazole after patent expiry is about 33%. Ranbaxy introduced the patented medicine Luliconazole in India in January 2010 under licence from a Japanese firm, Summit. In March 2016, it was the sole supplier and charged Rs 299 for 20 GM cream. After patent expiry, by June 2018, 39 other sellers were available at Rs 199.
Micafungin experiences a much smaller price erosion of about 9%. GSK introduced it in May 2010 and charged Rs 5911 for a 50 MG injection, 1 Ml. By June 2018, three other sellers were in the market. GSK reduced its price to Rs 5602, also available from a generic company at Rs 5389.
In short, markets like India do not show a specific trend for price erosion like the US and Europe. There are no good, reported studies on price erosion after patent expiration. However, it is safe to assume that generics would be available at about 50% of the brand price.
What is it for Semaglutide?
The price erosion would depend upon the number of players in the market and complexity. API process of Semaglutide is complex. The route from Fmoc-glycine 4-alkoxy benzyl alcohol resin is challenging to optimise. Many companies filed IP around the process.
As per the USFDA website, 37 DMFs were filed.
At least 7 ANDAs were filed for Ozempic, one for Wegovy and one for Rybelsus.
Sandoz declared their launch in Canada in 2026
Biocon expects to launch in Brazil in 2026
There will be generics in China in 2026, as per press releases by several companies.
So, this will be a highly competitive market, even though the API process is complex.
Many companies are planning the launch.
API and FDF dossiers are available on the market, but no one is willing to shoulder IP risk with this blockbuster product.
High capital expenditure could be necessary for Gxs to deliver billions of injection devices5. Reference here
API Price: USD 600-1000/GRAM
FDF India price: Tablets INR 3170 ($ 38) to INR 3870 ($ 45) for three variants6. Details here
Our view
Though this is a complex product, prices could erode by more than 50% since there will be many D1 entrants. If there are more than ten entrants on the D1, the price could be dropped to 30% of the Brand price.
How safe is Semaglutide today?
The most common adverse events included nausea, diarrhoea, vomiting, constipation, abdominal pain, headache, fatigue, indigestion, dizziness, and hypoglycemia in patients with diabetes
The most frequent reason for cessation is gastrointestinal adverse effects
A new study suggests that patients taking semaglutide — the active ingredient in Ozempic and Wegovy — may be at a higher risk of developing an eye condition that can cause blindness. Non-arteritic anterior ischemic optic neuropathy or NAION, happens when blood flow to the optic nerve is blocked, causing sudden, painless vision loss in one eye. A study published July 3 in JAMA Ophthalmology. More plaintiffs are continuing to join the diabetes drug Ozempic lawsuits against Novo Nordisk ahttps://www.jdsupra.com/legalnews/ozempic-lawsuit-update-new-study-links-2733216/
Our view:
Even though there are adverse reports, nothing will be proven soon.
Price erosion calculations for Semaglutide:
Methodology followed
The annual report of Novo Nordisk provides sales data for all Semaglutide brands in China and RoW markets up to CY 20237. Here
The growth rate for 2024 and 2025 is assumed to be constant. This is a reasonable assumption, as all market reports indicate that Ozempic's growth is phenomenal in 2024.
Oral dosage Rabelsus is not accounted for in this analysis as the IP situation around oral solid dosage form is very complicated, and the patent is being litigated in many jurisdictions. In our assessment, generic oral semaglutide will not be launched before 2033/2034.
Two scenarios were considered. Though erosion in the best-case scenario would start in March 2026, the entire year 2026 is considered for simplicity.
50% erosion in 2026
70% erosion in 2026
Case 1: 50% erosion, the situation would be as follows:
Total = USD mio 1743+ 1253 =~ USD 3 Bn
Case 2: 70% erosion, the situation would be as follows:
Total = USD mio 1046+ 752=~ USD 1.8 Bn
Our view:
Total Semaglutide sales in China and RoW after patent expiration in 2026 could be USD 1.8 bn to USD 3 bn.
PART II
The potential impact of generic Semaglutide launch on other GLPs
Liraglutide-Victoza
IP and regulatory scenario
Victoza is approved for type 2 diabetes, while Saxenda is approved for weight loss. Saxenda is used in a higher dosage than Victoza and has additional warnings and side effects. Both Victoza and Saxenda have lost basic patent protection as per Novo Nordisk. Here
Dose: 18MG/3ML (6MG/ML); subcutaneous
Generic launches in key countries in APAC, MENA, and Asia
Generic launch in the US was litigation-driven; Teva launched AG in June 20248, and others will follow. Here
In Europe, generics started launches.
Technical and Commercial Information
Key FDF players: Teva, Sandoz, Glenmark
DMF filers: 21
API Price: Many sources, such as DRL, MSN, etc. The API is priced at> USD 3000-5000/Gram.
API process: The probable synthetic route from Fmoc-Glycine is very complex.
FDF price: The branded (Victoza) price in India is about INR 5300/- (~$66/-), and Gx versions are priced at INR 1800 (~$ 22).
A comprehensive price comparison is here.9
Possibility of price erosion post-low-cost Semaglutide
Liraglutide is ~ $ 2 bn market.
There will be many generic launches, and soon, price erosion will occur. In SRMs, prices will be determined by price approval processes in respective countries.
Liraglutide is the first-generation GLP-1; it produces only a fraction of the weight loss that Wegovy or Zepbound can achieve.
Liraglutide price erosion would be normal like any other complex generics (ca. 25-40% of Brand), and it would not be driven by low-cost Semaglutide in 2026.
Dulaglutide
IP and regulatory Scenario
Dulaglutide, the active ingredient in Trulicity
Approved in 2014 Type 2 diabetes (T2D).
Dose: Inj 75 MG and 150 MG, once a week.
It is used to treat many patients with T2D, resulting in significant reductions in HbAlc with a low risk of hypoglycemia and reductions in body weight.
Generic launches in critical countries in APAC, MENA, and Asia
It is safe to assume only brand products are on the market.
This 2038 generic launch would be the most optimistic scenario. It is unlikely to happen; it is based on the expiration of WO2019103875A2
Technical and Commercial Information
Key FDF players: Only Brand product Eli Lilly.
DMF filers: - Nil (This is more than 40 amino acids and hence will not be considered a small molecule by the FDA)
API Price: No API supplier is available.
API process: Dulaglutide is a biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker.
FDF price: INR 5497 ( ~$70). Details here.10 Lupin is offering Eli Lilly’s product.
Possibility of price erosion post-low-cost Semaglutide
Though Dolaglutide is once a week, it is not yet approved for Type-1 diabetes or weight loss.
SUSTAIN trials with subcutaneous Semaglutide are not encouraging page 41 here (11)
On page 7 (here)11, GLP-1 patients and value market share from Feb 22 to Feb 24 show a declining trend for dulaglutide.
AWARD‐11 clinical study for weight loss is being conducted, and if it meets the endpoint, dulaglutide could compete with low-cost Semaglutide 12. Here
Price erosion and patient switches would depend on ongoing clinical studies.
Lixisenatide
IP and regulatory Scenario
Lixisenatide (trade name Lyxumia in the European Union and Adlyxin in the U.S.)
Once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes.
Sanofi withdrew the product from the US market in January 2023 for business reasons.13 Here
Generic launches in critical countries in APAC, MENA, and Asia
It is safe to assume only brand products are on the market. Generic launches could be as follows:
Technical and Commercial Information
Key FDF players: Only Brand product Sanofi
DMF filers: - Nil (There are 44 amino acids and hence will not be considered a small molecule by the FDA)
API Price: No API supplier is available.
API process: Lixisenatide is an Injectable form of naturally occurring peptide. No synthetic route has been published yet.
FDF price: Insulin Glargine (100u/ml) + Lixisenatide (0.05mg/ml): INR 1685 ($ 20). 14 Here
Possibility of price erosion post-low-cost Semaglutide
Lixisenatide is a once-a-day treatment, whereas Semaglutide is a once-a-week treatment.
Launching generic low-cost Semaglutide might affect the brands' sales (if they exit until the launch of low-cost Semaglutide) in ways other than technical reasons.
Sanofi withdrew the product in the US for business reasons in 2023 and may do so in other jurisdictions.
The patient shift from low-cost Semaglutide to lixisenatide will be unlikely.
Tirzepatide
IP and regulatory Scenario
Different dosages and dosage forms have been approved in the US since 2022. EU approval was in April 2024. It would enjoy 8+2+1 Years of Data Exclusivity in Europe.
Many strong patent families protect the product in different jurisdictions.
Generic launches are unlikely before 2036-2039.
Generic launches in critical countries in APAC, MENA, and Asia
No information is available in the public domain.
It is safe to assume only brand products are on the market. Generic launches could be as follows:
These are not LoE dates; these dates are based on a preliminary understanding of IP and regulatory scenarios.
Technical and Commercial Information
Key FDF players: Only Brand Eli Lilly
DMF filers: - 7
API process: The process is reported by Eli Lilly in WO2020159949 and appears very complex at first glance.
FDF price: US price information can be found here. (15)
Possibility of price erosion post-low-cost Semaglutide
Tirzepatide is superior to Semaglutide in reducing HbA1c levels and preventing hypoglycemia. Reference Here (16)
Tirzeptide was approved in India in July 2024, and similar situations would occur in other Asian, LatAm, and MENA countries.
Tirzepatide will be marketed as any other Branded product, and generic versions of Tirzepatide are far away.
Tirzepatide price will not be impacted by generic low-priced Semaglutide.
Conclusions:
Generic Semaglutide entries will be very eventful. The brand will do everything to deter generics from launching.
Semaglutide prices may drop to at least 50% in LRMs.
SRM generic entries will be in 2031.
Liraglutide and Dulaglutide prices will be impacted due to low-priced Semaglutide generic launches.
Novo Nordisk’s obesity drug monlunabant showed only modest weight loss in a Phase 2a trial.
In the short term, there might not be good competition for anti-obesity pills of semaglutide. However, this document does not focus too much on semaglutide pills, as generic competition for the pills is far away. (18).
https://finance.yahoo.com/news/novo-nordisk-shares-drop-more-141137692.html.
Orforglipron (LY-3502970) is an oral, non-peptide small molecule in early-phase clinical trials. It will be cheaper and easier to produce than GLP-1s, but it will take time to hit the market.
Total Semaglutide sales in China and RoW after patent expiration in 2026 could be USD 1.8 bn to USD 3 bn.
References
WO2006097537: https://patents.google.com/patent/WO2008047082A2/en
IQVIA report: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.iqvia.com/-/media/iqvia/pdfs/india/us-generics-market-evolution-of-indian-players.pdf
IQVIA report: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1200641/full
Impact of Product Patents on Pharmaceutical Market Structure and Prices in India http://facultylive.iimcal.ac.in/workingpapers
https://www.barrons.com/articles/generic-weight-loss-drugs-e5a1754c
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https://www.goodrx.com/zepbound/weight-loss-tirzepatide-cost
https://www.jdsupra.com/legalnews/ozempic-lawsuit-update-new-study-links-2733216/
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