Ivacaftor; lumacaftor - Generic Drug Details

What are the generic sources for ivacaftor; lumacaftor and what is the scope of patent protection?

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

Ivacaftor; lumacaftor has four hundred and fifty-eight patent family members in thirty-six countries.

One supplier is listed for this compound.

Summary for ivacaftor; lumacaftor

International Patents:	458
US Patents:	22
Tradenames:	1
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Clinical Trials:	36
DailyMed Link:	ivacaftor; lumacaftor at DailyMed

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

Constraining patent/regulatory exclusivity:

8,993,600

Dosage:

GRANULE;ORAL

Constraining patent/regulatory exclusivity:

8,993,600

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; lumacaftor

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

Sponsor	Phase
Qanatpharma Canada LTD	Phase 1
Children's Hospital Medical Center, Cincinnati	N/A
University of North Carolina	Early Phase 1

See all ivacaftor; lumacaftor clinical trials

Pharmacology for ivacaftor; lumacaftor

Drug Class	Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Mechanism of Action	Chloride Channel Activation Potentiators Cytochrome P450 2B6 Inducers Cytochrome P450 2C19 Inducers Cytochrome P450 2C8 Inducers Cytochrome P450 2C8 Inhibitors Cytochrome P450 2C9 Inducers Cytochrome P450 2C9 Inhibitors Cytochrome P450 3A Inducers Cytochrome P450 3A Inhibitors P-Glycoprotein Inducers P-Glycoprotein Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for ivacaftor; lumacaftor

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

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

US Patents and Regulatory Information for ivacaftor; lumacaftor

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	9,670,163		Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No	8,993,600		Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-003	Sep 2, 2022		RX	Yes	No	10,597,384		Y	Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No	11,564,916
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No	8,716,338		Y

EU/EMA Drug Approvals for ivacaftor; lumacaftor

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Vertex Pharmaceuticals (Ireland) Limited	Orkambi	lumacaftor, ivacaftor	EMEA/H/C/003954 Orkambi tablets are indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation in the CFTR gene.Orkambi granules are indicated for the treatment of cystic fibrosis (CF) in children aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.	Authorised	no	no	no	2015-11-19

International Patents for ivacaftor; lumacaftor

Country	Patent Number	Title	Estimated Expiration
China	102933206	Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
Spain	2900353
Hungary	E053357
Eurasian Patent Organization	201070698	ТВЕРДЫЕ ФОРМЫ 3-(6-(1-(2,2-ДИФТОРБЕНЗО[D][1,3]-ДИОКСОЛ-5-ИЛ)ЦИКЛОПРОПАНКАРБОКСАМИДО)-3-МЕТИЛПИРИДИН-2-ИЛ)БЕНЗОЙНОЙ КИСЛОТЫ
Israel	252421
Japan	2013523836

Supplementary Protection Certificates for ivacaftor; lumacaftor

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3170818	301060	Netherlands		PRODUCT NAME: EEN COMBINATIE VAN (A) 3-(6-(1-(2,2-DIFLUORBENZO(D)(1,3)DIOXOL-5-YL)CYCLOPROPAANCARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOEZUUR EN (B) N-(5-HYDROXY-2,4-DITERT-BUTYL-FENYL)-4-OXO-1H-CHINOLINE-3-CARBOXAMIDE OF EEN FARMACEUTISCH AANVAARDBAAR ZOUT DAARVAN; REGISTRATION NO/DATE: EU/1/15/1059 20151124
2404919	SPC/GB16/026	United Kingdom		PRODUCT NAME: LUMACAFTOR, OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, OR AN ESTER PRODRUG THEREOF; REGISTERED: UK EU/1/15/1059/001 20151124; UK EU/1/15/1059/002 20151124
1773816	300748	Netherlands		PRODUCT NAME: N-(5-HYDROXY-2,4-DI-TERT-BUTYL-FENYL)-4-OXO-1H-CHINOLINE-3-CARBOXAMIDE (INN: IVACAFTOR) OF EEN FARMACEUTISCH AANVAARDBAAR ZOUT DAARVAN; REGISTRATION NO/DATE: EU/1/12/782/001-002 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	C 2015 027	Romania		PRODUCT NAME: IVACAFTOR SAU O SARE ACCEPTABILA FARMACEUTIC A ACESTUIAN-(5-HIDROXI-2,4-DITERT-BUTIL-FENIL)-4-OXO-1H-CHINOLIN-3-CARBOXAMIDA SAU O SARE ACCEPTABILA FARMACEUTIC AACESTUIA; NATIONAL AUTHORISATION NUMBER: EU/1/12/782/001, EU/1/12/782/002; DATE OF NATIONAL AUTHORISATION: 20120723; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/12/782/001, EU/1/12/782/002; DATE OF FIRST AUTHORISATION IN EEA: 20120723
2225230	2017009	Norway		PRODUCT NAME: 3-6-(1-(2,2-DIFLUOR-1,3-; REG. NO/DATE: EU/1/15/1059 20151210

Ivacaftor; lumacaftor Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory of Lumacaftor-Ivacaftor

Introduction

Lumacaftor-ivacaftor, marketed under the brand name Orkambi, is a groundbreaking treatment for cystic fibrosis (CF) patients who are homozygous for the Phe508del mutation in the CFTR gene. This combination therapy has significantly impacted the management of CF, but its market dynamics and financial trajectory are complex and multifaceted.

Clinical Efficacy and Safety

The clinical efficacy of lumacaftor-ivacaftor has been well-documented. Studies have shown that the treatment improves lung function, reduces pulmonary exacerbations, and enhances nutritional status in patients who tolerate the therapy[1][3].

However, the safety profile is not without challenges. A significant number of patients discontinue treatment due to adverse events, particularly respiratory and non-respiratory adverse events. Factors such as adult age, low lung function (ppFEV1 < 40%), and frequent intravenous antibiotic courses before treatment initiation increase the risk of discontinuation[1].

Market Uptake and Revenue

The market uptake of lumacaftor-ivacaftor has been robust, driven by its approval by regulatory bodies such as the FDA and the European Medicines Agency. In 2017, Vertex Pharmaceuticals, the manufacturer, reported significant revenue growth from Orkambi, with third-quarter revenues of $336 million, a 44% increase from the previous year[2].

The total 2017 revenue guidance for Orkambi was increased to $1.29 to $1.32 billion, reflecting strong market demand and expanded patient access. This growth was part of a broader trend in CF product revenues, which saw a 34% increase in the third quarter of 2017 compared to the same period in 2016[2].

Financial Performance and Guidance

Vertex Pharmaceuticals' financial performance has been heavily influenced by the success of Orkambi. The company's combined GAAP and non-GAAP R&D and SG&A expenses were substantial, but the revenue growth from Orkambi and another CF drug, Kalydeco, helped drive non-GAAP net income to $136.4 million in the third quarter of 2017, a 216% increase from the previous year[2].

The financial guidance for 2017 was adjusted upward to reflect the strong performance of Orkambi and Kalydeco, with total CF product revenues expected to be between $2.10 and $2.15 billion. This adjustment underscored the market's positive response to these treatments and their financial impact on the company[2].

Cost-Effectiveness and Budget Impact

Despite its clinical benefits, the high cost of lumacaftor-ivacaftor has raised concerns about its cost-effectiveness and budget impact. A cost-effectiveness analysis (CEA) and budget impact analysis (BIA) were conducted to evaluate these aspects.

The CEA showed that while lumacaftor-ivacaftor improves FEV1% predicted and reduces pulmonary exacerbations, its high cost results in a significant average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER). The BIA indicated a substantial total budget impact, highlighting the need for careful consideration by health plans and payers[5].

Impact on Lung Microbiome and Metabolome

The treatment also has implications for the lung microbiome and metabolome. Studies have shown that lumacaftor-ivacaftor temporarily alters the respiratory microbial composition, particularly reducing the relative abundance of Pseudomonas aeruginosa. However, these changes are often transient and do not persist beyond 12 months. The metabolomic changes in the breath and sputum suggest a relationship with inflammation and oxidative stress rather than microbial metabolism[4].

Patient Access and Affordability

The high cost of lumacaftor-ivacaftor poses significant challenges for patient access and affordability. The drug's pricing has been a subject of debate, with many advocating for more affordable options to ensure that all eligible patients can benefit from this life-changing therapy.

Regulatory and Market Expansion

Regulatory approvals and label expansions have played a crucial role in the market dynamics of lumacaftor-ivacaftor. The drug has been approved for use in patients aged 2 and older with the Phe508del mutation, and ongoing clinical trials are exploring its efficacy in younger patients and those with different mutations[2].

Competitive Landscape

The CF treatment market is evolving, with new therapies and combinations being developed. The introduction of other CFTR modulators, such as tezacaftor-ivacaftor, has expanded treatment options for patients. However, lumacaftor-ivacaftor remains a key player in the market due to its established efficacy and widespread use[2].

Future Outlook

The future outlook for lumacaftor-ivacaftor is promising but complex. Ongoing research aims to improve its safety profile and expand its use to more patient populations. However, the financial and access challenges must be addressed to ensure that this valuable treatment reaches all who need it.

Key Takeaways

• Clinical Efficacy: Lumacaftor-ivacaftor improves lung function, reduces pulmonary exacerbations, and enhances nutritional status in CF patients.
• Market Uptake: Strong revenue growth driven by regulatory approvals and expanded patient access.
• Financial Performance: Significant revenue contribution to Vertex Pharmaceuticals, but high costs and substantial R&D and SG&A expenses.
• Cost-Effectiveness: High cost-effectiveness ratios and substantial budget impact, necessitating careful health plan considerations.
• Patient Access: Affordability challenges due to high pricing, affecting patient access.
• Regulatory and Market Expansion: Ongoing label expansions and clinical trials to explore broader patient populations.

FAQs

Q: What is the primary indication for lumacaftor-ivacaftor? A: Lumacaftor-ivacaftor is primarily indicated for the treatment of cystic fibrosis in patients who are homozygous for the Phe508del mutation in the CFTR gene.

Q: What are the common adverse events associated with lumacaftor-ivacaftor? A: Common adverse events include respiratory and non-respiratory adverse events, with respiratory events being more frequent, especially in patients with low lung function.

Q: How has the market responded to lumacaftor-ivacaftor? A: The market has responded positively, with significant revenue growth and expanded patient access following regulatory approvals.

Q: What are the cost-effectiveness concerns surrounding lumacaftor-ivacaftor? A: The high cost of the treatment results in significant cost-effectiveness ratios and budget impact, making it a challenge for health plans and payers.

Q: Are there ongoing studies to improve or expand the use of lumacaftor-ivacaftor? A: Yes, ongoing clinical trials are exploring the efficacy of lumacaftor-ivacaftor in younger patients and those with different mutations, as well as combinations with other treatments.

Sources

1. Real-Life Safety and Effectiveness of Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis. ATS Journals.
2. Vertex Reports Third-Quarter 2017 Financial Results. Vertex Pharmaceuticals.
3. Longitudinal changes in lung function following initiation of lumacaftor and ivacaftor. Cystic Fibrosis Journal.
4. Lumacaftor/ivacaftor changes the lung microbiome and metabolome in adult CF patients. European Respiratory Journal Open Research.
5. Cost-Effectiveness and Budget Impact of Lumacaftor/Ivacaftor in the Management of Cystic Fibrosis. PubMed.