Elexacaftor, ivacaftor, tezacaftor; ivacaftor - Generic Drug Details

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

Elexacaftor, ivacaftor, tezacaftor; ivacaftor is the generic ingredient in one branded drug marketed by Vertex Pharms Inc and is included in two NDAs. There are thirty-two patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Elexacaftor, ivacaftor, tezacaftor; ivacaftor has five hundred and four patent family members in forty-five countries.

One supplier is listed for this compound.

Summary for elexacaftor, ivacaftor, tezacaftor; ivacaftor

International Patents:	504
US Patents:	32
Tradenames:	1
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Clinical Trials:	21
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for elexacaftor, ivacaftor, tezacaftor; ivacaftor
DailyMed Link:	elexacaftor, ivacaftor, tezacaftor; ivacaftor at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for elexacaftor, ivacaftor, tezacaftor; ivacaftor

Constraining patent/regulatory exclusivity:

10,793,547

Dosage:

TABLET, TABLET;ORAL

Constraining patent/regulatory exclusivity:

10,793,547

Dosage:

GRANULES;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 elexacaftor, ivacaftor, tezacaftor; ivacaftor

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

Sponsor	Phase
Chiesi USA, Inc.	Phase 4
University of North Carolina, Chapel Hill	Phase 4
The Marcus Foundation, Inc.	Phase 4

See all elexacaftor, ivacaftor, tezacaftor; ivacaftor clinical trials

Anatomical Therapeutic Chemical (ATC) Classes for elexacaftor, ivacaftor, tezacaftor; ivacaftor

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

US Patents and Regulatory Information for elexacaftor, ivacaftor, tezacaftor; 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	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULES;ORAL	217660-001	Apr 26, 2023		RX	Yes	No	9,974,781		Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-002	Jun 8, 2021		RX	Yes	No	7,776,905		Y	Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULES;ORAL	217660-001	Apr 26, 2023		RX	Yes	No	8,410,274		Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULES;ORAL	217660-002	Apr 26, 2023		RX	Yes	Yes	10,272,046		Y

International Patents for elexacaftor, ivacaftor, tezacaftor; ivacaftor

Country	Patent Number	Title	Estimated Expiration
Canada	2869945	MODULATEURS DES TRANSPORTEURS DE CASSETTES DE LIAISON DE L'ATP (MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS)
China	102892764	Solid forms of (r)-1(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihyderoxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide
China	102497859	Pharmaceutical composition and administrations thereof
Portugal	3219705

Supplementary Protection Certificates for elexacaftor, ivacaftor, tezacaftor; ivacaftor

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1773816	237 5014-2015	Slovakia		PRODUCT NAME: N-(5-HYDROXY-2,4-DITERC-BUTYL-FENYL)-4-OXO- -1H-CHINOLIN-3-KARBOXAMID (IVACAFTOR); REGISTRATION NO/DATE: EU/1/12/782/001 - EU/1/12/782/002 20120725
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	C01773816/01	Switzerland		PRODUCT NAME: IVACAFTOR; REGISTRATION NO/DATE: SWISSMEDIC 62686 13.01.2014
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

Elexacaftor, ivacaftor, tezacaftor; ivacaftor Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for Elexacaftor, Tezacaftor, Ivacaftor (ELX-TEZ-IVA)

Introduction

Elexacaftor, tezacaftor, and ivacaftor (ELX-TEZ-IVA), commonly known as Trikafta, is a groundbreaking triple combination therapy for cystic fibrosis (CF). This treatment has significantly altered the management and outcomes of CF, but its market dynamics and financial trajectory are complex and multifaceted.

Clinical Efficacy and Impact

ELX-TEZ-IVA has demonstrated remarkable clinical efficacy in improving lung function, reducing pulmonary exacerbations, and enhancing the overall quality of life for patients with CF. Studies have shown substantial increases in percent predicted forced expiratory volume in the first second (ppFEV1) and significant reductions in pulmonary exacerbations compared to placebo and other CFTR modulators[3][4].

Market Adoption

The adoption of ELX-TEZ-IVA has been rapid, particularly in regions where it has been approved and reimbursed. In the UK, for example, the proportion of patients taking ELX-TEZ-IVA increased to 86% by December 2022, reflecting its preference over earlier CFTR modulators like lumacaftor-ivacaftor (LUM-IVA) and tezacaftor-ivacaftor (TEZ-IVA)[2].

Cost-Effectiveness and Economic Evaluations

Despite its clinical benefits, the cost-effectiveness of ELX-TEZ-IVA is a significant concern. Economic evaluations by health technology assessment bodies such as CADTH and NICE have highlighted the high costs associated with this treatment. In CADTH's analysis, the incremental cost-effectiveness ratio (ICER) for ELX-TEZ-IVA compared to best supportive care (BSC) ranged from $1,284,953 to $1,644,869 per quality-adjusted life-year (QALY) gained, depending on the genotype. This is far beyond the conventional willingness-to-pay threshold of $50,000 per QALY[1].

Pricing and Commercial Arrangements

The high cost of ELX-TEZ-IVA is a major barrier to its widespread adoption. The treatment is priced at approximately £14,000 per 56-sachet pack in the UK, excluding VAT. However, commercial arrangements with health services like the NHS can provide discounts, though the exact sizes of these discounts are confidential[2].

Long-Term Uncertainties

There are significant uncertainties regarding the long-term clinical efficacy and cost-effectiveness of ELX-TEZ-IVA. Current data are limited to a maximum follow-up period of 192 weeks, and there is no evidence on the long-term impact on the rate of decline in lung function or pulmonary exacerbations beyond this period[1].

Patient and Carer Impact

The financial burden of caring for someone with CF is substantial, and the introduction of ELX-TEZ-IVA has had a mixed impact. While the treatment has improved the quality of life for patients and their carers, the financial strain remains significant. Many carers have had to leave their jobs to care for family members with CF, highlighting the broader economic implications[2].

Regulatory and Reimbursement Landscape

Regulatory approvals and reimbursement decisions play a crucial role in the market dynamics of ELX-TEZ-IVA. In the UK, NICE has recommended the use of ELX-TEZ-IVA based on its clinical effectiveness and the commercial arrangements in place. However, the cost-effectiveness remains a point of contention, and ongoing negotiations between manufacturers and health authorities are necessary to ensure sustainable access[2].

Future Outlook

The future outlook for ELX-TEZ-IVA is influenced by several factors, including ongoing clinical trials, pricing negotiations, and the development of new CF treatments. As more data become available on its long-term efficacy and safety, there may be adjustments in its cost-effectiveness evaluations. Additionally, any price reductions or changes in commercial arrangements could significantly impact its market trajectory[1][3].

Key Drivers of Cost

The primary drivers of the high costs associated with ELX-TEZ-IVA are the drug acquisition costs and the assumptions about its long-term benefits. For ELX-TEZ-IVA to be considered cost-effective at conventional thresholds, a price reduction in excess of 94% would be required[1].

Patient Submissions and Expert Testimonies

Patient submissions and expert testimonies have highlighted the transformative impact of ELX-TEZ-IVA on the lives of individuals with CF. Patients have reported better physical health, mental wellbeing, increased energy levels, and fewer medical interventions. These benefits underscore the need for continued access to this treatment despite its high costs[2].

Conclusion

The market dynamics and financial trajectory of ELX-TEZ-IVA are characterized by its exceptional clinical efficacy, high costs, and complex regulatory and reimbursement landscape. While it has revolutionized the treatment of CF, its long-term cost-effectiveness remains uncertain. Ongoing negotiations and future clinical data will be crucial in determining its sustainable place in the market.

Key Takeaways

• Clinical Efficacy: ELX-TEZ-IVA significantly improves lung function and reduces pulmonary exacerbations.
• High Costs: The treatment is associated with high drug acquisition costs, making it challenging to meet conventional cost-effectiveness thresholds.
• Regulatory Approvals: NICE and CADTH have evaluated its cost-effectiveness, with NICE recommending its use under certain conditions.
• Patient Impact: The treatment has transformed the lives of patients and their carers, despite the financial burden.
• Future Outlook: Ongoing clinical trials and pricing negotiations will influence its future market trajectory.

FAQs

Q: What are the primary clinical benefits of ELX-TEZ-IVA? A: ELX-TEZ-IVA improves lung function, reduces pulmonary exacerbations, and enhances overall quality of life for patients with CF.

Q: Why is ELX-TEZ-IVA considered expensive? A: The high drug acquisition costs and the assumptions about its long-term benefits drive the high costs associated with ELX-TEZ-IVA.

Q: What are the regulatory bodies' stances on ELX-TEZ-IVA? A: NICE has recommended its use under certain conditions, while CADTH has highlighted its high ICER values, indicating it is not cost-effective at conventional thresholds.

Q: How has ELX-TEZ-IVA impacted patients and carers? A: Patients and carers have reported significant improvements in physical health, mental wellbeing, and reduced treatment burden, despite the financial challenges.

Q: What are the future prospects for ELX-TEZ-IVA? A: Ongoing clinical trials, pricing negotiations, and the development of new CF treatments will influence its future market trajectory and cost-effectiveness.

Sources

1. CADTH Pharmacoeconomic Review: Elexacaftor-Tezacaftor-Ivacaftor and Ivacaftor for Cystic Fibrosis.
2. NICE Guidance: Ivacaftor–tezacaftor–elexacaftor, tezacaftor–ivacaftor and lumacaftor–ivacaftor for treating cystic fibrosis.
3. NCBI Clinical Review: Elexacaftor-Tezacaftor-Ivacaftor and Ivacaftor for Cystic Fibrosis.
4. MDPI Article: Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination Therapy for Cystic Fibrosis.