TENOFOVIR ALAFENAMIDE FUMARATE - Generic Drug Details

What are the generic drug sources for tenofovir alafenamide fumarate and what is the scope of freedom to operate?

Tenofovir alafenamide fumarate is the generic ingredient in three branded drugs marketed by Lupin Ltd, Apotex, and Gilead Sciences Inc, and is included in three NDAs. There are three patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Tenofovir alafenamide fumarate has one hundred and thirty-two patent family members in fifty countries.

There are six drug master file entries for tenofovir alafenamide fumarate. One supplier is listed for this compound. There is one tentative approval for this compound.

Summary for TENOFOVIR ALAFENAMIDE FUMARATE

International Patents:	132
US Patents:	3
Tradenames:	3
Applicants:	3
NDAs:	3
Drug Master File Entries:	6
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	113
Clinical Trials:	82
Patent Applications:	488
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for TENOFOVIR ALAFENAMIDE FUMARATE
DailyMed Link:	TENOFOVIR ALAFENAMIDE FUMARATE at DailyMed

Recent Clinical Trials for TENOFOVIR ALAFENAMIDE FUMARATE

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

Sponsor	Phase
ANRS, Emerging Infectious Diseases	Phase 3
Assistance Publique - Hôpitaux de Paris, FRANCE	Phase 3
Ministry of Health, Thailand	Phase 3

See all TENOFOVIR ALAFENAMIDE FUMARATE clinical trials

Generic filers with tentative approvals for TENOFOVIR ALAFENAMIDE FUMARATE

Applicant	Application No.	Strength	Dosage Form
		EQ 25MG BASE	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 TENOFOVIR ALAFENAMIDE FUMARATE

Drug Class	Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
Mechanism of Action	Nucleoside Reverse Transcriptase Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for TENOFOVIR ALAFENAMIDE FUMARATE

J05AF	Nucleoside and nucleotide reverse transcriptase inhibitors
J05A	DIRECT ACTING ANTIVIRALS
J05	ANTIVIRALS FOR SYSTEMIC USE
J	Antiinfectives for systemic use

Paragraph IV (Patent) Challenges for TENOFOVIR ALAFENAMIDE FUMARATE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
VEMLIDY	Tablets	tenofovir alafenamide fumarate	25 mg	208464	6	2019-11-05

US Patents and Regulatory Information for TENOFOVIR ALAFENAMIDE FUMARATE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Gilead Sciences Inc	VEMLIDY	tenofovir alafenamide fumarate	TABLET;ORAL	208464-001	Nov 10, 2016	AB	RX	Yes	Yes					Y
Gilead Sciences Inc	VEMLIDY	tenofovir alafenamide fumarate	TABLET;ORAL	208464-001	Nov 10, 2016	AB	RX	Yes	Yes					Y
Lupin Ltd	TENOFOVIR ALAFENAMIDE	tenofovir alafenamide fumarate	TABLET;ORAL	214226-001	Mar 30, 2023	AB	RX	No	No
Gilead Sciences Inc	VEMLIDY	tenofovir alafenamide fumarate	TABLET;ORAL	208464-001	Nov 10, 2016	AB	RX	Yes	Yes					Y
Gilead Sciences Inc	VEMLIDY	tenofovir alafenamide fumarate	TABLET;ORAL	208464-001	Nov 10, 2016	AB	RX	Yes	Yes
Apotex	TENOFOVIR ALAFENAMIDE FUMARATE	tenofovir alafenamide fumarate	TABLET;ORAL	213867-001	Mar 21, 2024		DISCN	No	No

Expired US Patents for TENOFOVIR ALAFENAMIDE FUMARATE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Gilead Sciences Inc	VEMLIDY	tenofovir alafenamide fumarate	TABLET;ORAL	208464-001	Nov 10, 2016

International Patents for TENOFOVIR ALAFENAMIDE FUMARATE

Country	Patent Number	Title	Estimated Expiration
Japan	2015038149	テノホビルアラフェナミドヘミフマレート (TENOFOVIR ALAFENAMIDE HEMIFUMARATE)
Canada	2893174
Montenegro	02612	TENOFOVIR ALAFENAMID HEMIFUMARAT (TENOFOVIR ALAFENAMIDE HEMIFUMARATE)
Colombia	6880063	Hemifumarato de tenofovir alafenamida
Norway	20030270
Poland	2744810

Supplementary Protection Certificates for TENOFOVIR ALAFENAMIDE FUMARATE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1663240	PA2015038	Lithuania		PRODUCT NAME: RILPIVIRINUM + TENOFOVIRUM DISOPROXILUM; REGISTRATION NO/DATE: EU/1/11/737/001, 2011 11 28, EU/1/11/737/002 20111128
2924034	C02924034/01	Switzerland		PRODUCT NAME: DORAVIRIN, LAMIVUDIN UND TENOFOVIRDISOPROXIL; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 67066 17.12.2019
2924034	132019000000062	Italy		PRODUCT NAME: DORAVIRINA O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE IN COMBINAZIONE CON LAMIVUDINA O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE IN COMBINAZIONE CON TENOFOVIR O UN SUO ESTERE, IN PARTICOLARE UN ESTERE DI DISOPROXIL O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE, IN PARTICOLARE UN SALE FUMARATO(DELSTRIGO); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/18/1333/001-002, 20181127
1301519	11/2016	Austria		PRODUCT NAME: TENOFOVIRALAFENAMID ODER EIN SALZ ODER SOLVAT DAVON, INSBESONDERE TENOFOVIRALAFENAMIDFUMARAT; REGISTRATION NO/DATE: EU/1/15/1061/001-002 (MITTEILUNG) 20151123
1663240	93382	Luxembourg		PRODUCT NAME: COMBINAISON DE RILPIVIRINE OU UNE FORME THERAPEUTIQUE EQUIVALENTE QUI EN DERIVE TELLE QUE PROTEGEE PAR LE BREVET DE BASE, TEL QU'UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE RILPIVIRINE, INCLUANT LE SEL CHLORHYDRATE DE RILPIVIRINE ET TENOFOVIR ALAFENAMIDE, OU UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, EN PARTICULIER LE FUMARATE DE TENOFOVIR ALAFENAMIDE; AUTHORISATION NUMBER AND DATE: EU/1/16/1112 ODEFSEY - EMTRICITABINE
1663240	379 5033-2016	Slovakia		PRODUCT NAME: RILPIVIRIN VO VSETKYCH FORMACH CHRANENYCH ZAKLADNYM PATENTOM/TENOFOVIR-ALAFENAMID VO VSETKYCH FORMACH CHRA- NENYCH ZAKLADNYM PATENTOM; REGISTRATION NO/DATE: EU/1/16/1112 20160623

TENOFOVIR ALAFENAMIDE FUMARATE Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for Tenofovir Alafenamide Fumarate

Introduction

Tenofovir alafenamide fumarate (TAF) is a crucial antiviral medication used in the treatment of HIV and chronic hepatitis B. Its market dynamics and financial trajectory are influenced by several factors, including clinical efficacy, market competition, and regulatory environments.

Clinical Efficacy and Preference

TAF is preferred over its predecessor, tenofovir disoproxil fumarate (TDF), due to its lower dosing requirements and reduced side effects, such as decreased bone mineral density and renal proximal tubular dysfunction[5].

Clinical Considerations

• TAF is more readily absorbed in target cells, resulting in higher concentrations of the active agent TFV-diphosphate with lower serum exposure to tenofovir. This makes it a safer option for patients with osteoporosis or impaired kidney function[5].
• The World Health Organization (WHO) recommends TAF for special circumstances, including adults and adolescents with established osteoporosis or impaired kidney function, and as an alternative regimen for children weighing at least 25kg[1].

Market Demand and Adoption

Global Fund Procurement

• As of 2024, an increasing number of Global Fund-supported countries are adopting TAF, despite initial limited procurement. This trend is driven by the need for equitable treatment options for people living with HIV (PLHIV) who cannot take TDF[1].

Market Expansion

• The global market for TAF is projected to expand significantly from 2023 to 2031, driven by increasing demand and the upward trend in market dynamics[4].

Financial Implications

Cost and Budget Impact

• TAF-based products are approximately 30% more expensive than TDF-based products. For instance, $1 million can treat 2,242 PLHIV annually with TLD (a TDF-based regimen) compared to 1,388 with TAFED (a TAF-based regimen)[1].
• The higher cost of TAF can significantly impact grant budgets and the scale-up of HIV treatment coverage.

Revenue and Sales

• Gilead Sciences, the primary manufacturer of TAF-based products, reported significant revenue growth. For example, sales of Biktarvy (a combination therapy including TAF) increased by 24% year-over-year in the second quarter of 2021, and Vemlidy (TAF for hepatitis B) sales increased by 32% during the same period[3].

Patent and Generic Challenges

• TAF products are facing potential patent challenges, with multiple companies filing Drug Master Files (DMFs) for tenofovir alafenamide fumarate. However, the timeline for generic entry can be long due to evolving standards of care and the complexity of antiviral treatments[2].

Market Competition and Pricing

Pricing Dynamics

• The pricing of TAF-based products is expected to be influenced by the potential for lower prices at higher volumes due to the lower amount of active pharmaceutical ingredient (API) needed[1].
• The market competition is also driven by the availability of generic alternatives, although the entry of generics into the market is slower for antiviral products compared to other therapeutic areas[2].

Programmatic and Supply Chain Considerations

Implementation Challenges

• Introducing TAF-based products into national health programs increases the complexity of delivering first-line regimens for PLHIV. This requires updates to in-country guidelines, healthcare worker training, and integration into supply chain systems[1].

Supply Chain Efficiency

• TAF products offer advantages such as smaller pill and bottle sizes, which are preferable for both patients and supply chains. However, there is a potential increase in stock-out risks due to the reliance on multiple first-line products[1].

Regulatory Environment

Approval and Recommendations

• TAF has been approved by regulatory bodies such as the FDA for the treatment of HIV and chronic hepatitis B. The WHO recommendations also support its use in specific circumstances[1][5].

Ongoing Studies and Efficacy

• Ongoing Phase 3 trials have demonstrated the efficacy of TAF in treating hepatitis B, showing non-inferior results compared to TDF[5].

Financial Performance of Key Players

Gilead Sciences

• Gilead Sciences has seen significant financial growth driven by the sales of TAF-based products. In the second quarter of 2021, total product sales increased by 21% to $6.2 billion, with Biktarvy and Vemlidy contributing substantially to this growth[3].

Future Outlook

Market Projections

• The global TAF market is expected to continue its upward trend, driven by increasing demand and the expanding use of TAF in various therapeutic areas[4].

Challenges and Opportunities

• While the higher cost of TAF poses challenges, the potential for lower prices at higher volumes and the increasing adoption by health programs present opportunities for market growth and financial stability.

Key Takeaways

• TAF offers clinical advantages over TDF, including lower dosing and reduced side effects.
• The market demand for TAF is increasing, driven by its adoption in Global Fund-supported countries and other health programs.
• The financial trajectory of TAF is influenced by its higher cost, patent challenges, and regulatory approvals.
• Gilead Sciences has seen significant revenue growth from TAF-based products.
• The future outlook is positive, with projected market expansion and potential for lower prices at higher volumes.

FAQs

What are the clinical advantages of TAF over TDF?

TAF is more readily absorbed in target cells, resulting in higher concentrations of the active agent TFV-diphosphate with lower serum exposure to tenofovir. This reduces side effects such as decreased bone mineral density and renal proximal tubular dysfunction.

How does the cost of TAF compare to TDF?

TAF-based products are approximately 30% more expensive than TDF-based products, which can significantly impact grant budgets and the scale-up of HIV treatment coverage.

What are the potential challenges for generic entry into the TAF market?

Generic challengers face long timelines due to evolving standards of care and the complexity of antiviral treatments. Additionally, the risk of devoting resources to a product that may not be the standard of care by the time it reaches the market is a significant consideration.

How has Gilead Sciences' financial performance been affected by TAF sales?

Gilead Sciences has seen significant financial growth driven by the sales of TAF-based products, such as Biktarvy and Vemlidy, which contributed substantially to the company's revenue increase in 2021.

What are the programmatic challenges associated with introducing TAF into national health programs?

Introducing TAF-based products increases the complexity of delivering first-line regimens for PLHIV, requiring updates to in-country guidelines, healthcare worker training, and integration into supply chain systems.

Sources

1. Briefing Note Managing Tenofovir Alafenamide (TAF) Demand. The Global Fund, July 11, 2024.
2. Tenofovir alafenamide fumarate raises targeting questions. Clarivate, October 17, 2019.
3. Gilead Sciences Announces Second Quarter 2021 Financial Results. Business Wire, July 29, 2021.
4. Global Tenofovir Alafenamide Fumarate Tablets Market Size, Trends. Market Research Intellect.
5. 208464Orig1s000 - accessdata.fda.gov. FDA, January 11, 2016.