Ivacaftor - Generic Drug Details

What are the generic sources for ivacaftor and what is the scope of freedom to operate?

Ivacaftor is the generic ingredient in three branded drugs marketed by Vertex Pharms Inc and Vertex Pharms, and is included in five NDAs. There are forty-three patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Ivacaftor has two hundred and fifty-five patent family members in thirty-three countries.

There are three drug master file entries for ivacaftor. One supplier is listed for this compound. There is one tentative approval for this compound.

Summary for ivacaftor

International Patents:	255
US Patents:	43
Tradenames:	3
Applicants:	2
NDAs:	5
Drug Master File Entries:	3
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	104
Clinical Trials:	126
Patent Applications:	1,473
Drug Prices:	Drug price trends for ivacaftor
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for ivacaftor
What excipients (inactive ingredients) are in ivacaftor?	ivacaftor excipients list
DailyMed Link:	ivacaftor at DailyMed

See drug prices for ivacaftor

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

Constraining patent/regulatory exclusivity:

8,883,206

Dosage:

GRANULE;ORAL

Constraining patent/regulatory exclusivity:

10,646,481

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 ivacaftor

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

Sponsor	Phase
Qanatpharma Canada LTD	Phase 1
University of North Carolina, Chapel Hill	Phase 4
Chiesi USA, Inc.	Phase 4

See all ivacaftor clinical trials

Generic filers with tentative approvals for IVACAFTOR

Applicant	Application No.	Strength	Dosage Form
		150MG	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 ivacaftor

Drug Class	Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Mechanism of Action	Chloride Channel Activation Potentiators Cytochrome P450 2C9 Inhibitors Cytochrome P450 3A Inhibitors P-Glycoprotein Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for ivacaftor

R07AX	Other respiratory system products
R07A	OTHER RESPIRATORY SYSTEM PRODUCTS
R07	OTHER RESPIRATORY SYSTEM PRODUCTS
R	Respiratory system

Paragraph IV (Patent) Challenges for IVACAFTOR

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
KALYDECO	Oral Granules	ivacaftor	25 mg, 50 mg and 75 mg	207925	1	2022-04-13
KALYDECO	Tablets	ivacaftor	150 mg	203188	1	2020-06-10

US Patents and Regulatory Information for ivacaftor

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No	8,324,242
Vertex Pharms Inc	SYMDEKO (COPACKAGED)	ivacaftor; ivacaftor, tezacaftor	TABLET;ORAL	210491-002	Jun 21, 2019		RX	Yes	No	9,931,334		Y
Vertex Pharms Inc	SYMDEKO (COPACKAGED)	ivacaftor; ivacaftor, tezacaftor	TABLET;ORAL	210491-001	Feb 12, 2018		RX	Yes	Yes	10,206,877		Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	TABLET;ORAL	206038-001	Jul 2, 2015		RX	Yes	Yes	10,646,481		Y
Vertex Pharms Inc	KALYDECO	ivacaftor	GRANULE;ORAL	207925-004	May 3, 2023		RX	Yes	No
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-002	Aug 7, 2018		RX	Yes	Yes	8,754,224		Y	Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	TABLET;ORAL	206038-002	Sep 28, 2016		RX	Yes	No	8,993,600		Y

EU/EMA Drug Approvals for ivacaftor

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Vertex Pharmaceuticals (Ireland) Limited	Kalydeco	ivacaftor	EMEA/H/C/002494 Kalydeco tablets are indicated:As monotherapy for the treatment of adults, adolescents, and children aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4.4 and 5.1).In a combination regimen with tezacaftor/ivacaftor tablets for the treatment of adults, adolescents, and children aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G, and 3849+10kbC→T.In a combination regimen with ivacaftor/tezacaftor/elexacaftor tablets for the treatment of adults, adolescents, and children aged 6 years and older with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene (see section 5.1).Kalydeco granules are indicated for the treatment of infants aged at least 4 months, toddlers and children weighing 5 kg to less than 25 kg with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4.4 and 5.1).	Authorised	no	no	no	2012-07-23

International Patents for ivacaftor

Country	Patent Number	Title	Estimated Expiration
Cyprus	1118980
Poland	2502911
European Patent Office	2502912	Modulateurs de transporteurs de cassette de liaison à l ́ATP (Modulators of ATP-binding cassette transporters)
Japan	2014111656	PHARMACEUTICAL COMPOSITION AND ADMINISTRATIONS THEREOF
Mexico	365890	MODULADORES DE TRANSPORTADORES CON CASETE DE UNIÓN CON ATP. (MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS.)
Canada	2783314	4-OXO-1H-QUINOLINE-3-CARBOXAMIDES UTILES COMME MODULATEURS DES TRANSPORTEURS DE CASSETTE SE LIANT A L'ATP (4-OXO-1H-QUINOLINE-3-CARBOXAMIDES AS MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS)
Cyprus	1119963

Supplementary Protection Certificates for ivacaftor

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1773816	CR 2015 00038	Denmark		PRODUCT NAME: N-(5-HYDROXY-2,4-DITERT-BUTYL-PHENYL)-4-OXO-1H-QUINOLIN-3-CARBOXAMID ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF; REG. NO/DATE: EU/1/12/782/001-002 20120725
1773816	C01773816/01	Switzerland		PRODUCT NAME: IVACAFTOR; REGISTRATION NO/DATE: SWISSMEDIC 62686 13.01.2014
1773816	C20150028 00162	Estonia		PRODUCT NAME: IVAKAFTOOR;REG NO/DATE: EU/1/12/782/001-002 25.07.2012
2826776	2021C/517	Belgium		PRODUCT NAME: SYMKEVI - TEZACAFTOR/IVACAFTOR; EEN COMBINATIE VAN (A) (R)-1-(2,2-DIFLUOROBENZO(D)(1,3)DIOXOL-5-YL)-N-(1-(2,3-DIHYDROXYPROPYL)-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL)CYCLOPROPANECARBOXAMIDE OF EEN VANUIT FARMACEUTISCH OOGPUNT GESCHIKT ZOUT DAARVAN EN (B) N-(5-HYDROXY-2,4-DITERT-BUTYL-PHENYL)-4-OXO-1H-QUINOLINE-3-CARBOXAMIDE OF EEN VANUIT FARMACEUTISCH OOGPUNT GESCHIKT ZOUT DAARVAN; AUTHORISATION NUMBER AND DATE: EU/1/18/1306 20181106
1773816	35/2015	Austria		PRODUCT NAME: N-(5-HYDROXY-2,4DITERT-BUTYL-PHENYL)-4-OXO-1H-QUINOLIN-3-CARBOXAMID ODER EIN PHARMAZEUTISCH ANNEHMBARES SALZ DAVON; REGISTRATION NO/DATE: EU/1/12/782/001, EU/1/12/782/002 (MITTEILUNG) 20120725
2826776	132021000000062	Italy		PRODUCT NAME: UNA COMBINAZIONE DI (A) TEZACAFTOR O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE E (B) IVACAFTOR O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE(SYMKEVI); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/18/1306, 20181106
3170818	2020C/005	Belgium		PRODUCT NAME: ORKAMBI (LUMACAFTOR + IVACAFTOR); AUTHORISATION NUMBER AND DATE: EU/1/15/1059 20151124

Ivacaftor Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory of Ivacaftor

Introduction

Ivacaftor, a groundbreaking treatment for cystic fibrosis (CF) patients, particularly those with the G551D genetic mutation, has significantly impacted the CF therapeutics market. This article delves into the market dynamics and financial trajectory of ivacaftor, highlighting its clinical efficacy, cost implications, and market performance.

Clinical Efficacy of Ivacaftor

Ivacaftor has demonstrated substantial clinical benefits for CF patients. Studies have shown that it improves lung function, increases life expectancy, and enhances quality-adjusted life-years (QALYs). For patients with the G551D mutation, ivacaftor is associated with an average of 18.25 additional life-years and 15.03 additional QALYs compared to usual care alone[1].

Cost Implications

Despite its clinical efficacy, ivacaftor comes with a high cost. The incremental lifetime cost of ivacaftor is estimated at $3,374,584, with the drug costing $426.72 per tablet[1]. However, the budget impact analysis indicates that this cost translates to a relatively limited budget impact of $0.087 per member per month over a 3-year time horizon[1].

Market Performance

Revenue Growth

Ivacaftor, marketed as Kalydeco, has been a significant contributor to the revenue of Vertex Pharmaceuticals. In the third quarter of 2017, Kalydeco generated $213 million in revenue, representing a 22% increase from the previous year[2]. This trend continued, with Kalydeco being one of the top-selling drugs for Vertex, along with other CF treatments like Orkambi and Symdeko[4].

Market Expansion

The global cystic fibrosis therapeutics market, driven in part by ivacaftor and other CFTR modulators, is expected to reach $20.9 billion by 2031, growing at a CAGR of 7.8%[4]. The adoption of new CFTR-targeting therapies, including ivacaftor, has been a key factor in this market expansion.

Competitive Landscape

Dominance of Vertex Pharmaceuticals

Vertex Pharmaceuticals dominates the CF therapeutics market, with ivacaftor being a cornerstone of their product portfolio. The company's triple combination regimen, Trikafta (elexacaftor/tezacaftor/ivacaftor), has further solidified their position, addressing approximately 90% of the CF patient population[4].

Regulatory and Pricing Challenges

Despite its dominance, Vertex faces regulatory and pricing challenges, particularly in Europe where governments have imposed restrictions due to the high cost of treatment. The list price for Trikafta, which includes ivacaftor, is $311,503 per year, highlighting the ongoing debate about the affordability of these life-saving treatments[4].

Financial Trajectory of Vertex Pharmaceuticals

Quarterly and Annual Revenues

In the third quarter of 2017, Vertex's total CF product revenues were $549.6 million, with Kalydeco contributing significantly to this figure[2]. By 2023, Vertex's full-year product revenue had increased to $9.87 billion, an 11% increase from the previous year, with continued growth projected for 2024[3].

Research and Development Expenses

The development and marketing of ivacaftor and other CF treatments have been supported by substantial research and development (R&D) investments. In the third quarter of 2017, Vertex's non-GAAP R&D expenses were $243.2 million, driven by the clinical development of their triple combination regimens for CF[2].

Impact on Patient Care and Life Expectancy

Improved Life Expectancy

The introduction of ivacaftor and other CFTR modulators has significantly improved the life expectancy of CF patients. The mean life expectancy has increased to 37 years, with continued improvements expected as new treatments are adopted[4].

Quality of Life

Ivacaftor has not only extended life but also improved the quality of life for CF patients. Studies have shown that treatment with ivacaftor significantly improves growth in prepubertal children and enhances overall lung function[5].

Future Outlook

New Drug Applications and Pipeline

Vertex is on track to submit new drug applications for additional CF treatments, including the Vanzacaftor Triple, by mid-2024. Their broad and deep clinical-stage pipeline continues to advance across multiple disease areas, ensuring ongoing innovation in CF therapeutics[3].

Market Growth and Challenges

The CF therapeutics market is expected to continue growing, driven by the adoption of new treatments. However, challenges related to the high cost of treatment and limited availability for all mutations will need to be addressed to ensure equitable access to these life-saving therapies[4].

Key Takeaways

• Clinical Efficacy: Ivacaftor significantly improves life expectancy and quality-adjusted life-years for CF patients.
• Cost Implications: Despite high costs, ivacaftor has a relatively limited budget impact.
• Market Performance: Ivacaftor has been a key revenue driver for Vertex Pharmaceuticals.
• Competitive Landscape: Vertex dominates the CF therapeutics market, but faces regulatory and pricing challenges.
• Financial Trajectory: Vertex's revenues have consistently grown, supported by significant R&D investments.
• Impact on Patient Care: Ivacaftor has improved life expectancy and quality of life for CF patients.

FAQs

What is the primary genetic mutation targeted by ivacaftor?

Ivacaftor primarily targets the G551D genetic mutation in cystic fibrosis patients.

How much does ivacaftor cost per tablet?

The cost of ivacaftor per tablet is approximately $426.72[1].

What is the estimated incremental lifetime cost of ivacaftor?

The estimated incremental lifetime cost of ivacaftor is $3,374,584[1].

How has ivacaftor impacted the life expectancy of CF patients?

Ivacaftor has increased the life expectancy of CF patients by an average of 18.25 additional life-years[1].

What is the projected market size for the global cystic fibrosis therapeutics market by 2031?

The global cystic fibrosis therapeutics market is expected to reach $20.9 billion by 2031[4].

Sources

1. Forecasting US ivacaftor outcomes and cost in cystic fibrosis ... - ERS Publications
2. Vertex Reports Third-Quarter 2017 Financial Results - Vertex Pharmaceuticals
3. Vertex Reports Fourth Quarter and Full Year 2023 Financial Results - Vertex Pharmaceuticals
4. Global Cystic Fibrosis Therapeutics Market $20.9 Billion by 2031 - iHealthcareAnalyst
5. Growth in Prepubertal Children With Cystic Fibrosis Treated With ... - Pediatrics