Difelikefalin acetate - Generic Drug Details

What are the generic drug sources for difelikefalin acetate and what is the scope of freedom to operate?

Difelikefalin acetate is the generic ingredient in one branded drug marketed by Cara Therap and is included in one NDA. There are twelve patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Difelikefalin acetate has fifty patent family members in twenty-five countries.

One supplier is listed for this compound.

Summary for difelikefalin acetate

International Patents:	50
US Patents:	12
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
DailyMed Link:	difelikefalin acetate at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for difelikefalin acetate

Dosage:

SOLUTION;INTRAVENOUS

^*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.

Pharmacology for difelikefalin acetate

Drug Class	Kappa Opioid Receptor Agonist
Mechanism of Action	Opioid kappa Receptor Agonists

Anatomical Therapeutic Chemical (ATC) Classes for difelikefalin acetate

V03AX	Other therapeutic products
V03A	ALL OTHER THERAPEUTIC PRODUCTS
V03	ALL OTHER THERAPEUTIC PRODUCTS
V	Various

US Patents and Regulatory Information for difelikefalin acetate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes			Y	Y
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes				Y
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes			Y	Y
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes			Y	Y
Cara Therap	KORSUVA	difelikefalin acetate	SOLUTION;INTRAVENOUS	214916-001	Aug 23, 2021		RX	Yes	Yes			Y	Y

International Patents for difelikefalin acetate

Country	Patent Number	Title	Estimated Expiration
Cyprus	2022032
Japan	2010509343
China	101535336	Synthetic peptide amides and dimers thereof
Israel	197924	אמידים פפטידים סינתטיים, תכשירים רוקחים המכילים אותם ושימושים שלהם (Synthetic peptide amides, pharmaceutical compositions comprising the same and uses thereof)
Hungary	S2200045
Slovenia	2064228
Russian Federation	2500685	СИНТЕТИЧЕСКИЕ ПЕПТИДНЫЕ АМИДЫ (SYNTHETIC PEPTIDE AMIDES)

Supplementary Protection Certificates for difelikefalin acetate

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2064228	C20220035 00379	Estonia		PRODUCT NAME: DIFELIKEFALIIN;REG NO/DATE: EU/1/22/1643 27.04.2022
2064228	CA 2022 00045	Denmark		PRODUCT NAME: DIFELIKEFALIN IN ALL FORMS COVERED BY THE BASIC PATENT; REG. NO/DATE: EU/1/22/1643 20220427
2064228	PA2022522	Lithuania		PRODUCT NAME: DIFELIKEFALINAS, BET KOKIA FORMA, KURIAI TAIKOMA PAGRINDINIO PATENTO APSAUGA ; REGISTRATION NO/DATE: EU/1/22/1643 20220425
2064228	C202230052	Spain		PRODUCT NAME: DIFELICEFALINA, OPCIONALMENTE EN FORMA DE UNA SAL FARMACEUTICAMENTE ACEPTABLE,HIDRATO, SOLVATO, HIDRATO DE SAL DE ACIDO O N-OXIDO; NATIONAL AUTHORISATION NUMBER: EU/1/22/1643; DATE OF AUTHORISATION: 20220425; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/22/1643; DATE OF FIRST AUTHORISATION IN EEA: 20220425
2064228	22C1054	France		PRODUCT NAME: DIFELIKEFALINE DANS TOUTES LES FORMES PROTEGEES PAR LE BREVET DE BASE; REGISTRATION NO/DATE: EU/1/22/1643 20220427
2064228	301199	Netherlands		PRODUCT NAME: DIFELIKEFALIN, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AANVAARDBAAR ZOUT, HYDRAAT, SOLVAAT, ZUURZOUT-HYDRAAT OF N-OXIDE; REGISTRATION NO/DATE: EU/1/22/1643 20220427
2064228	2022C/546	Belgium		PRODUCT NAME: DIFELIKEFALINE SOUS TOUTES LES FORMES COUVERTES PAR LE BREVET DE BASE; AUTHORISATION NUMBER AND DATE: EU/1/22/1643 20220427

Difelikefalin acetate Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for Difelikefalin Acetate

Introduction

Difelikefalin acetate, marketed as KORSUVA® or Kapruvia, is a groundbreaking treatment for moderate-to-severe pruritus associated with chronic kidney disease (CKD) in patients undergoing hemodialysis. This article delves into the market dynamics and financial trajectory of this innovative drug.

Mechanism of Action and Safety Profile

Difelikefalin is a kappa opioid receptor agonist with a unique peptidic structure that distinguishes it from other opioid agonists. It primarily acts on the peripheral nervous system, minimizing the risk of central nervous system (CNS) side effects such as respiratory depression and abuse potential[1][3].

Clinical Efficacy

The drug has demonstrated significant efficacy in large-scale clinical trials, including the KALM-1 and KALM-2 trials. These trials showed that difelikefalin significantly improved the Worst Itch Numeric Rating Scale (WI-NRS) scores in patients, with 52% and 50% of patients achieving at least a 3-point improvement in the WI-NRS score from baseline to week 12 in the KALM-1 and KALM-2 trials, respectively[4].

Market Approval and Availability

Difelikefalin is the only approved treatment for CKD-associated pruritus (CKD-aP) in the U.S. and Europe. It is distributed through specialized clinics, primarily dialysis centers, which helps in minimizing the potential for diversion and abuse[1][3].

Financial Performance

Revenue Generation

In the first quarter of 2024, KORSUVA® generated net sales of approximately $1.8 million. During this period, wholesalers shipped 111,720 vials to dialysis centers. The total revenue for the first quarter included $0.8 million in collaborative revenue, $0.6 million in commercial supply revenue, and $0.6 million in other revenue related to royalty payments[2].

For the full year 2023, total revenue was $12.9 million, with $12.9 million coming from collaborative revenue related to the profit share from CSL Vifor’s sales of KORSUVA injection. Commercial supply revenue was $5.8 million, and there was an additional $0.9 million from license and milestone fees[5].

Sales and Distribution

The drug is sold through a partnership with CSL Vifor, and the revenue is generated through both collaborative and commercial supply agreements. In 2023, the company received a significant regulatory milestone payment from Maruishi Pharmaceuticals Co. Ltd. for the marketing approval of KORSUVA injection in Japan[5].

Cash Runway and Financial Projections

Cara Therapeutics, the developer of difelikefalin, has extended its cash runway into 2026 through strategic financial management, including a Royalty Purchase and Sale Agreement with HealthCare Royalty for up to $40 million. This financial stability is crucial for the ongoing development and commercialization of difelikefalin[5].

Market Uptake and Patient Population

The estimated population size for CKD-aP patients is significant, although the exact proportion is uncertain. The KALM-1 and KALM-2 trials indicated that a substantial number of patients were using anti-itch medications and had other specified medical conditions, highlighting the need for effective treatments like difelikefalin[4].

Competitive Landscape

Difelikefalin stands out in the market due to its unique mechanism of action and improved safety profile compared to other treatments for CKD-aP, which are often used off-label and may have limited efficacy and higher toxicity risks[1].

Regulatory Environment

The drug has been approved by regulatory bodies in the U.S. and Europe, and it is not recommended for scheduling under the Controlled Substances Act (CSA) due to its lack of abuse potential. This regulatory approval and the restricted access to healthcare professionals further support its market position[3].

Future Developments

Cara Therapeutics is prioritizing the development of oral difelikefalin for the treatment of pruritus associated with notalgia paresthetica and other conditions. The company has completed enrollment in the KOURAGE 1 Part A trial and is planning further clinical trials, which could expand the market for difelikefalin[5].

Key Takeaways

• Efficacy and Safety: Difelikefalin has demonstrated strong efficacy and a favorable safety profile in treating CKD-aP.
• Market Approval: It is the only approved treatment for CKD-aP in the U.S. and Europe.
• Financial Performance: The drug has generated significant revenue through collaborative and commercial supply agreements.
• Market Uptake: The market uptake is promising, with a substantial patient population and limited competition.
• Future Developments: Ongoing clinical trials and strategic financial management position difelikefalin for continued growth.

FAQs

What is difelikefalin acetate used for?

Difelikefalin acetate, marketed as KORSUVA® or Kapruvia, is used for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD) in patients undergoing hemodialysis.

How does difelikefalin differ from other opioid agonists?

Difelikefalin is a kappa opioid receptor agonist that primarily acts on the peripheral nervous system, minimizing CNS side effects and abuse potential, unlike other opioid agonists.

What are the key clinical trial results for difelikefalin?

In the KALM-1 and KALM-2 trials, difelikefalin significantly improved the Worst Itch Numeric Rating Scale (WI-NRS) scores in patients, with 52% and 50% of patients achieving at least a 3-point improvement from baseline to week 12, respectively.

How much revenue has KORSUVA® generated in recent quarters?

In the first quarter of 2024, KORSUVA® generated net sales of approximately $1.8 million. For the full year 2023, total revenue was $12.9 million.

What are the future development plans for difelikefalin?

Cara Therapeutics is prioritizing the development of oral difelikefalin for the treatment of pruritus associated with notalgia paresthetica and other conditions, with ongoing clinical trials and strategic financial management.

Sources

1. Difelikefalin for the treatment of moderate-to-severe pruritus ... - Tandfonline
2. Cara Therapeutics Reports First Quarter 2024 Financial Results - Cara Therapeutics
3. 214916Orig1s000 - accessdata.fda.gov - FDA
4. Difelikefalin (Korsuva) - Canada's Drug Agency - CADTH Reimbursement Review
5. Cara Therapeutics Announces Fourth Quarter and Full Year 2023 - Cara Therapeutics