EMPAGLIFLOZIN; LINAGLIPTIN - Generic Drug Details

What are the generic sources for empagliflozin; linagliptin and what is the scope of freedom to operate?

Empagliflozin; linagliptin is the generic ingredient in two branded drugs marketed by Boehringer Ingelheim and is included in two NDAs. There are nineteen patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Empagliflozin; linagliptin has five hundred and sixty-two patent family members in forty-seven countries.

One supplier is listed for this compound. There are three tentative approvals for this compound.

Summary for EMPAGLIFLOZIN; LINAGLIPTIN

International Patents:	562
US Patents:	19
Tradenames:	2
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Clinical Trials:	23
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for EMPAGLIFLOZIN; LINAGLIPTIN
DailyMed Link:	EMPAGLIFLOZIN; LINAGLIPTIN at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for EMPAGLIFLOZIN; LINAGLIPTIN

Constraining patent/regulatory exclusivity:

8,551,957*PED

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for EMPAGLIFLOZIN; LINAGLIPTIN

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Diabetes & Endocrinology Foundation	N/A
Medanta, The Medicity, India	N/A
Wuxi People's Hospital	N/A

See all EMPAGLIFLOZIN; LINAGLIPTIN clinical trials

Generic filers with tentative approvals for EMPAGLIFLOZIN; LINAGLIPTIN

Applicant	Application No.	Strength	Dosage Form
		25MG;5MG	TABLET;ORAL
		25MG/5MG	TABLET;ORAL
		10MG/5MG	TABLET; ORAL

The 'tentative' approval signifies that the product meets all FDA standards for marketing, and, but for the patents / regulatory protections, it would approved.

Pharmacology for EMPAGLIFLOZIN; LINAGLIPTIN

Drug Class	Dipeptidyl Peptidase 4 Inhibitor Sodium-Glucose Cotransporter 2 Inhibitor
Mechanism of Action	Dipeptidyl Peptidase 4 Inhibitors Sodium-Glucose Transporter 2 Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for EMPAGLIFLOZIN; LINAGLIPTIN

A10BH	Dipeptidyl peptidase 4 (DPP-4) inhibitors
A10B	BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
A10	DRUGS USED IN DIABETES
A	Alimentary tract and metabolism

A10BK	Sodium-glucose co-transporter 2 (SGLT2) inhibitors
A10B	BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
A10	DRUGS USED IN DIABETES
A	Alimentary tract and metabolism

Paragraph IV (Patent) Challenges for EMPAGLIFLOZIN; LINAGLIPTIN

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
GLYXAMBI	Tablets	empagliflozin; linagliptin	10 mg/5 mg and 25 mg/5 mg	206073	9	2018-08-01

US Patents and Regulatory Information for EMPAGLIFLOZIN; LINAGLIPTIN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-001	Jan 30, 2015		RX	Yes	No	8,551,957*PED				Y
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-002	Jan 30, 2015		RX	Yes	Yes	7,407,955*PED				Y
Boehringer Ingelheim	TRIJARDY XR	empagliflozin; linagliptin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	212614-002	Jan 27, 2020		RX	Yes	No	7,713,938*PED				Y
Boehringer Ingelheim	TRIJARDY XR	empagliflozin; linagliptin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	212614-002	Jan 27, 2020		RX	Yes	No	7,579,449*PED				Y
Boehringer Ingelheim	TRIJARDY XR	empagliflozin; linagliptin; metformin hydrochloride	TABLET, EXTENDED RELEASE;ORAL	212614-001	Jan 27, 2020		RX	Yes	No	8,551,957*PED				Y

Expired US Patents for EMPAGLIFLOZIN; LINAGLIPTIN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-002	Jan 30, 2015	7,459,428
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-002	Jan 30, 2015	8,178,541
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-001	Jan 30, 2015	8,119,648
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-001	Jan 30, 2015	6,303,661
Boehringer Ingelheim	GLYXAMBI	empagliflozin; linagliptin	TABLET;ORAL	206073-002	Jan 30, 2015	6,303,661

EU/EMA Drug Approvals for EMPAGLIFLOZIN; LINAGLIPTIN

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Boehringer Ingelheim International GmbH	Glyxambi	empagliflozin, linagliptin	EMEA/H/C/003833 Glyxambi, fixed dose combination of empagliflozin and linagliptin, is indicated in adults aged 18 years and older with type 2 diabetes mellitus:to improve glycaemic control when metformin and/or sulphonylurea (SU) and one of the monocomponents of Glyxambi do not provide adequate glycaemic control;when already being treated with the free combination of empagliflozin and linagliptin.	Authorised	no	no	no	2016-11-11

International Patents for EMPAGLIFLOZIN; LINAGLIPTIN

Country	Patent Number	Title	Estimated Expiration
China	105377267	Therapeutic uses of empagliflozin
Ukraine	100221	СПОСОБ ПОЛУЧЕНИЯ ХИРАЛЬНЫХ 8-(3-АМИНОПИПЕРИДИН-1-ИЛ)КСАНТИНОВ;СПОСІБ ОДЕРЖАННЯ ХІРАЛЬНИХ 8-(3-АМІНОПІПЕРИДИН-1-ІЛ)КСАНТИНІВ (METHOD FOR PRODUCING CHIRAL 8-(3-AMINO-PIPERIDIN-1-YL)-XANTHINES)
New Zealand	572863	USES OF DPP-IV INHIBITORS
Portugal	2397142
Poland	3029040

Supplementary Protection Certificates for EMPAGLIFLOZIN; LINAGLIPTIN

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1532149	11C0052	France		PRODUCT NAME: LINAGLIPTINE SES ENANTIOMERES ET SELS; REGISTRATION NO/DATE: EU/1/11/707/001 20110830
1730131	PA2014035,C1730131	Lithuania		PRODUCT NAME: EMPAGLIFLOZINUM; REGISTRATION NO/DATE: EU/1/14/930 20140522
1532149	621	Finland
2187879	C20170016 00337	Estonia		PRODUCT NAME: EMPAGLIFLOSIIN/LINAGLIPTIIN;REG NO/DATE: EU/1/16/1146 15.11.2016
1532149	2011C/038	Belgium		PRODUCT NAME: 8-(3-AMINOPIPERIDIN-1-YL)-7-BUT-2-INYL-3-METHYL-1-(4-METHYLCHINAZOLIN-2--YLMETHYL)-3,7-DIHYDROPURIN-2,6-DIONE SES ENANTIOMERES OU L'UN DES SES SELS, EN PARTICULIER LA LINAGLIPTINE; AUTHORISATION NUMBER AND DATE: EU/1/11/707/001 20110830

EMPAGLIFLOZIN; LINAGLIPTIN Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for Empagliflozin and Linagliptin

Introduction

Empagliflozin and linagliptin are two significant drugs in the treatment of type 2 diabetes, each belonging to different classes of antidiabetic medications. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, while linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. This article delves into the market dynamics and financial trajectory of these drugs, highlighting their impact on the antidiabetic market.

Market Dynamics of Empagliflozin

Sales Growth

Empagliflozin, marketed under the brand name Jardiance, has seen significant growth in sales since its introduction. From 2014 to 2021, the sales of empagliflozin increased dramatically, from $1 million to $355 million, respectively. This growth is attributed to its efficacy in reducing blood glucose levels and its additional benefits such as weight loss and cardiovascular risk reduction[1].

Combination Therapies

Empagliflozin is often used in combination with other antidiabetic drugs, including linagliptin and metformin. These combination therapies have shown superior efficacy in reducing HbA1c levels compared to monotherapies. For instance, the combination of empagliflozin and linagliptin significantly reduced HbA1c levels and achieved better glycemic control in patients with type 2 diabetes[2][4][5].

Regulatory Approvals

The FDA has approved various formulations of empagliflozin, including a triple fixed-dose combination (FDC) with linagliptin and metformin. This approval has expanded the treatment options for patients with type 2 diabetes, enhancing the drug's market presence[4].

Market Dynamics of Linagliptin

Sales Performance

Linagliptin, marketed under the brand name Tradjenta, has maintained a stable market presence. From 2012 to 2021, its sales ranged from $170 million to $514 million, indicating a consistent demand for this DPP-4 inhibitor. The drug's sales have been driven by its efficacy as an add-on therapy to metformin and other antidiabetic medications[1].

Combination Therapies

Similar to empagliflozin, linagliptin is often used in combination with other drugs. The combination of linagliptin with empagliflozin has been particularly effective, showing significant reductions in HbA1c levels and weight loss. These combination therapies have contributed to linagliptin's continued market relevance[2][4][5].

Clinical Efficacy

Clinical trials have consistently shown that linagliptin, when used alone or in combination with other antidiabetic drugs, is effective in reducing blood glucose levels without increasing the risk of hypoglycemia. This safety profile has been a key factor in its market success[2][5].

Financial Trajectory of Empagliflozin and Linagliptin

Revenue Growth

The revenue generated by empagliflozin and linagliptin has been substantial. Empagliflozin's sales grew from $0 million in 2012 to $355 million in 2021, while linagliptin's sales peaked at $514 million in 2020. These figures reflect the increasing adoption of these drugs in the treatment of type 2 diabetes[1].

Impact on Eli Lilly's Financials

Eli Lilly, the manufacturer of both drugs, has seen significant financial benefits from their sales. In Q1 2023, Jardiance (empagliflozin) was one of the growth products that contributed to an 18% increase in revenue for Eli Lilly's growth products segment, reaching $4.56 billion. This growth underscores the financial importance of these drugs to the company[3].

Market Competition

The antidiabetic market is highly competitive, with various classes of drugs vying for market share. However, the combination therapies involving empagliflozin and linagliptin have carved out a niche, offering a competitive edge due to their efficacy and safety profiles. This competitive advantage has helped maintain their financial trajectory despite market pressures[2][4][5].

Clinical Efficacy and Safety

Glycemic Control

Both empagliflozin and linagliptin have demonstrated significant reductions in HbA1c levels when used alone or in combination. For example, the combination of empagliflozin 25 mg and linagliptin 5 mg reduced HbA1c levels by 1.8% in patients with baseline HbA1c levels of 8.5% or greater[5].

Weight Loss and Cardiovascular Benefits

Empagliflozin has additional benefits such as weight loss and cardiovascular risk reduction, which have contributed to its popularity. The combination with linagliptin maintains these benefits while enhancing glycemic control[2][5].

Safety Profile

The safety profile of both drugs is favorable, with low rates of hypoglycemia and other adverse events. This safety profile has been a crucial factor in their market success and continued use in clinical practice[2][4].

Regulatory and Clinical Developments

FDA Approvals

The FDA has approved various formulations and combinations of empagliflozin and linagliptin, including the triple FDC with metformin. These approvals have expanded treatment options and reinforced the market position of these drugs[4].

Clinical Trials

Several clinical trials have evaluated the efficacy and safety of empagliflozin and linagliptin, both as monotherapies and in combination. These trials have consistently shown positive outcomes, supporting their use in clinical practice[2][4][5].

Market Trends and Future Outlook

Increasing Demand for Combination Therapies

The trend towards combination therapies is expected to continue, driven by the superior efficacy and convenience of these regimens. This trend is likely to benefit both empagliflozin and linagliptin, as they are often used together or with other antidiabetic drugs[2][4][5].

Expanding Indications

The potential for expanding indications, such as the use of empagliflozin in cardiovascular disease management, could further boost the market for these drugs. Ongoing research and clinical trials may uncover additional benefits, enhancing their market trajectory[3].

Key Takeaways

• Sales Growth: Empagliflozin and linagliptin have shown significant sales growth, driven by their efficacy and safety profiles.
• Combination Therapies: The combination of empagliflozin and linagliptin has been particularly effective, offering superior glycemic control and additional benefits like weight loss.
• Regulatory Approvals: FDA approvals for various formulations, including the triple FDC with metformin, have expanded treatment options and reinforced their market position.
• Clinical Efficacy: Both drugs have demonstrated significant reductions in HbA1c levels and a favorable safety profile.
• Financial Impact: These drugs have contributed substantially to Eli Lilly's financial performance, particularly within the growth products segment.

FAQs

Q: What is the primary mechanism of action of empagliflozin? A: Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which works by reducing glucose reabsorption in the kidneys, thereby lowering blood glucose levels.

Q: How does linagliptin differ from empagliflozin in terms of its mechanism of action? A: Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which works by increasing the levels of incretin hormones, enhancing the release of insulin when glucose levels are elevated, and decreasing the release of glucagon.

Q: What are the benefits of combining empagliflozin and linagliptin? A: The combination of empagliflozin and linagliptin offers superior glycemic control, weight loss, and a favorable safety profile, including low rates of hypoglycemia.

Q: Have there been any significant regulatory approvals for the combination of empagliflozin and linagliptin? A: Yes, the FDA has approved a triple fixed-dose combination (FDC) of empagliflozin, linagliptin, and metformin, expanding treatment options for patients with type 2 diabetes.

Q: How have empagliflozin and linagliptin impacted Eli Lilly's financial performance? A: Both drugs have contributed significantly to Eli Lilly's revenue, particularly within the growth products segment, with Jardiance (empagliflozin) being one of the key drivers of revenue growth in recent years.

Sources

1. Market Intelligence Report: Antidiabetic Drugs, 2012-2021. Canada.ca.
2. Combination of Empagliflozin and Linagliptin as Second-Line Therapy for Type 2 Diabetes. Diabetes Care.
3. Eli Lilly and Company Q1 2023 Financial Results. Investor.Lilly.com.
4. Triple Fixed-Dose Combination Empagliflozin, Linagliptin, and Metformin XR. Tandfonline.com.
5. Type 2 Diabetes: Investigational Empagliflozin/Linagliptin Combination Tablet. Investor.Lilly.com.