PROGRAF Drug Patent Profile

Which patents cover Prograf, and what generic alternatives are available?

Prograf is a drug marketed by Astellas and is included in three NDAs.

The generic ingredient in PROGRAF is tacrolimus. There are twenty drug master file entries for this compound. Thirty-six suppliers are listed for this compound. Additional details are available on the tacrolimus profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Prograf

A generic version of PROGRAF was approved as tacrolimus by SANDOZ on August 10^th, 2009.

Summary for PROGRAF

US Patents:	0
Applicants:	1
NDAs:	3
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	405
Drug Prices:	Drug price information for PROGRAF
What excipients (inactive ingredients) are in PROGRAF?	PROGRAF excipients list
DailyMed Link:	PROGRAF at DailyMed

See drug prices for PROGRAF

See drug sales revenues for PROGRAF

Recent Clinical Trials for PROGRAF

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

Sponsor	Phase
Massachusetts General Hospital	PHASE4
Veloxis Pharmaceuticals	PHASE4
University Hospital, Limoges	PHASE4

See all PROGRAF clinical trials

Pharmacology for PROGRAF

Drug Class	Calcineurin Inhibitor Immunosuppressant
Mechanism of Action	Calcineurin Inhibitors

US Patents and Regulatory Information for PROGRAF

PROGRAF is protected by zero US patents and one FDA Regulatory Exclusivity.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Astellas	PROGRAF	tacrolimus	CAPSULE;ORAL	050708-003	Aug 24, 1998	AB	RX	Yes	No
Astellas	PROGRAF	tacrolimus	FOR SUSPENSION;ORAL	210115-001	May 24, 2018		RX	Yes	No
Astellas	PROGRAF	tacrolimus	CAPSULE;ORAL	050708-001	Apr 8, 1994	AB	RX	Yes	No
Astellas	PROGRAF	tacrolimus	CAPSULE;ORAL	050708-002	Apr 8, 1994	AB	RX	Yes	Yes
Astellas	PROGRAF	tacrolimus	INJECTABLE;INJECTION	050709-001	Apr 8, 1994	AP	RX	Yes	Yes

Expired US Patents for PROGRAF

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Astellas	PROGRAF	tacrolimus	INJECTABLE;INJECTION	050709-001	Apr 8, 1994

EU/EMA Drug Approvals for PROGRAF

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Astellas Pharma Europe B.V.	Modigraf	tacrolimus	EMEA/H/C/000954Prophylaxis of transplant rejection in adult and paediatric, kidney, liver or heart allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult and paediatric patients.	Authorised	no	no	no	2009-05-15
Astellas Pharma Europe BV	Advagraf	tacrolimus	EMEA/H/C/000712Prophylaxis of transplant rejection in adult kidney or liver allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	no	no	no	2007-04-23
Chiesi Farmaceutici S.p.A.	Envarsus	tacrolimus	EMEA/H/C/002655Prophylaxis of transplant rejection in adult kidney or liver allograft recipients. Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	no	no	no	2014-07-18
LEO Pharma A/S	Protopic	tacrolimus	EMEA/H/C/000374Flare treatmentAdults and adolescents (16 years of age and above)Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids.Children (two years of age and above)Treatment of moderate to severe atopic dermatitis in children (two years of age and above) who failed to respond adequately to conventional therapies such as topical corticosteroids.Maintenance treatmentMaintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in patients experiencing a high frequency of disease exacerbations (i.e. occurring four or more times per year) who have had an initial response to a maximum of six weeks treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).	Authorised	no	no	no	2002-02-27
Teva B.V.	Tacforius	tacrolimus	EMEA/H/C/004435Prophylaxis of transplant rejection in adult kidney or liver allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients.	Authorised	yes	no	no	2017-12-08

International Patents for PROGRAF

See the table below for patents covering PROGRAF around the world.

Country	Patent Number	Title	Estimated Expiration
Ireland	75221	A pharmaceutical solution comprising derivatives of FK506
Hungary	209436	PROCESS FOR PRODUCING PHARMACEUTICAL SOLUTIONS CONTAINING MACROLIDES
Germany	69122418
Austria	143598
Portugal	96916	PROCESSO PARA A PREPARACAO DE COMPOSICOES FARMACEUTICAS CONTENDO UM MACROLIDO

PROGRAF: Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

Market Performance Overview

PROGRAF (tacrolimus) generated $1.1 billion in net sales for Astellas Pharma Inc. in the fiscal year ended March 31, 2023. This represents a 5.6% increase from the prior fiscal year's $1.04 billion. The drug’s primary indication is the prevention of organ rejection in kidney, liver, and heart transplant patients. It is also utilized in the treatment of atopic dermatitis.

The immunosuppressant market segment, where PROGRAF competes, is projected to grow at a compound annual growth rate (CAGR) of 4.8% from 2023 to 2030, reaching an estimated $31.3 billion by 2030. This growth is driven by an increasing number of organ transplant procedures and a rising incidence of autoimmune diseases.

Patent Landscape and Generic Competition

PROGRAF's original composition of matter patent has expired in major markets, including the United States (2012) and Europe (2013). This expiration has led to the introduction of generic tacrolimus products, increasing competition and putting downward pressure on pricing.

Key generic competitors include:

• Aurobindo Pharma: Launched a generic version of PROGRAF in the U.S. in 2017.
• Teva Pharmaceuticals: Also offers a generic tacrolimus product.
• Viatris (formerly Mylan): Markets a generic tacrolimus formulation.

Astellas has actively defended its market share through authorized generic strategies and by focusing on differentiated formulations and delivery methods. The company's extended-release formulation, Astagraf XL, received FDA approval in 2014 and offers once-daily dosing, a distinct advantage over the twice-daily dosing of immediate-release tacrolimus. Astagraf XL is protected by its own set of patents, some of which extend into the mid-2030s.

Geographic Sales Breakdown

As of the fiscal year ended March 31, 2023:

• Japan: Accounted for approximately 30% of PROGRAF's total net sales, totaling $330 million.
• North America: Contributed around 45% of net sales, amounting to $495 million.
• Europe: Represented about 20% of net sales, or $220 million.
• Other Regions: Made up the remaining 5%, totaling $55 million.

The U.S. market remains the largest single contributor to PROGRAF's revenue, with Astagraf XL playing a significant role in maintaining market share against generic competition.

Financial Performance Analysis

Astellas's oncology and urology segments are key growth drivers. PROGRAF, as a mature product, contributes stable revenue but is not a primary engine for growth. Its financial trajectory is characterized by:

• Stable Revenue Base: Despite generic entry, PROGRAF and its authorized generics continue to generate substantial revenue.
• Margin Pressure: Generic competition typically leads to lower average selling prices, impacting gross margins.
• R&D Reinvestment: Astellas reinvests a significant portion of its revenue into research and development to identify and commercialize new therapeutic agents, offsetting the declining growth potential of its established products. In FY2023, R&D expenditure was approximately 15% of total net sales.

PROGRAF Net Sales Trend (USD Billions)

Fiscal Year	Net Sales	Year-over-Year Change
2021	1.02	-1.9%
2022	1.04	1.9%
2023	1.10	5.6%

Source: Astellas Pharma Inc. Annual Reports

The increase in FY2023 reflects improved performance in the U.S. market, driven by Astagraf XL.

Therapeutic Area Dynamics

Organ Transplantation

The demand for organ transplants globally is increasing due to factors such as an aging population, rising rates of chronic diseases leading to organ failure (e.g., diabetes, hypertension), and improvements in surgical techniques.

• Kidney Transplants: This is the most common type of organ transplant. In 2022, over 25,000 kidney transplants were performed in the U.S. [1].
• Liver Transplants: The second most frequent, with approximately 9,000 procedures in the U.S. in 2022 [1].
• Heart Transplants: Around 4,000 procedures were conducted in the U.S. in 2022 [1].

The effectiveness of tacrolimus in reducing acute rejection rates and improving long-term graft survival solidifies its position as a cornerstone therapy.

Atopic Dermatitis

PROGRAF is also indicated for the topical treatment of moderate to severe atopic dermatitis in patients who are not adequately responsive to or who are unable to tolerate conventional therapies. The market for atopic dermatitis treatments is competitive, with biologics and new topical agents emerging. However, PROGRAF's established efficacy profile supports its continued use in certain patient populations.

Regulatory Environment and Market Access

Astellas navigates a complex regulatory landscape. Key considerations include:

• FDA and EMA Approvals: Maintaining existing approvals and seeking label expansions where appropriate.
• Post-Marketing Surveillance: Ongoing monitoring for safety and efficacy.
• Pricing and Reimbursement: Negotiating favorable reimbursement from payers in various markets. Generic tacrolimus products have significantly altered the pricing dynamics, forcing branded products to focus on value-added services and differentiated formulations.

The U.S. FDA has approved multiple generic versions of immediate-release tacrolimus capsules and ointments, intensifying competition for the original PROGRAF formulation.

Competitive Landscape

The immunosuppressant market is diverse, featuring several drug classes:

• Calcineurin Inhibitors (CNIs): Tacrolimus and cyclosporine. PROGRAF competes directly with generic tacrolimus and cyclosporine-based products.
• mTOR Inhibitors: Sirolimus, everolimus.
• Antiproliferative Agents: Mycophenolate mofetil, azathioprine.
• Biologics: Basiliximab, alemtuzumab, belatacept. These newer agents often target specific pathways and can offer different efficacy and safety profiles, particularly in complex cases or for patients intolerant to CNIs.

Astellas's strategy to counter generic erosion involves:

1. Authorized Generics: Releasing its own generic version to capture market share and revenue that might otherwise go to third-party generics.
2. Formulation Innovation: Developing and marketing extended-release or topical formulations (Astagraf XL, Protopic) with patent protection.
3. Lifecycle Management: Exploring new indications or delivery methods for existing tacrolimus molecules.

Future Outlook

PROGRAF's revenue is expected to stabilize, with growth primarily driven by Astagraf XL and its continued use in the transplant market. The overall immunosuppressant market is robust, but PROGRAF's market share within this space will face ongoing pressure from generics.

Astellas's long-term strategy relies on its pipeline of novel therapeutics in areas such as oncology, genitourinary, and immunology. PROGRAF's contribution will shift from a primary growth driver to a significant revenue stabilizer within Astellas's portfolio.

The company may explore further lifecycle extensions for tacrolimus, such as combination therapies or novel delivery systems, to maintain its competitive edge. However, the primary patent expirations have fundamentally altered the market dynamics, making significant volume growth for the original PROGRAF formulation unlikely.

Key Takeaways

• PROGRAF generated $1.1 billion in net sales for Astellas in FY2023, a 5.6% increase, indicating sustained performance despite generic competition.
• The expiration of core patents has led to the introduction of generic tacrolimus, intensifying market competition and impacting pricing.
• Astellas has mitigated generic impact through authorized generics and differentiated formulations like Astagraf XL, whose patents extend into the mid-2030s.
• The organ transplantation market, PROGRAF's primary indication, continues to grow, driven by increasing transplant volumes globally.
• The U.S. remains the largest market for PROGRAF, with Astagraf XL contributing significantly to its revenue.

Frequently Asked Questions

1. What are the primary indications for PROGRAF? PROGRAF is indicated for the prevention of organ rejection in kidney, liver, and heart transplant patients and for the topical treatment of moderate to severe atopic dermatitis.

2. When did PROGRAF's original patents expire? The original composition of matter patents for PROGRAF expired in the United States in 2012 and in Europe in 2013.

3. How has Astellas responded to generic competition for PROGRAF? Astellas has employed strategies including the release of authorized generics, the development of differentiated formulations such as Astagraf XL (extended-release), and lifecycle management initiatives.

4. What is the projected growth rate for the immunosuppressant market? The immunosuppressant market is projected to grow at a CAGR of 4.8% from 2023 to 2030.

5. Which geographic regions contribute the most to PROGRAF's sales? North America and Japan are the largest geographic contributors to PROGRAF's net sales, accounting for approximately 45% and 30%, respectively, as of FY2023.

Citations

[1] Organ Procurement and Transplantation Network. (2023). OPTN Data Summary: 2022 Annual Data Report. U.S. Department of Health and Human Services. Retrieved from https://optn.transplant.hrsa.gov/data/