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-four 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
Veloxis Pharmaceuticals	PHASE4
Massachusetts General Hospital	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 three FDA Regulatory Exclusivities.

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	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	5,260,301

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

International Patents for PROGRAF

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

Country	Patent Number	Title	Estimated Expiration
Canada	2037408	SOLUTION MACROLIDE PHARMACEUTIQUE NON-AQUEUSE (A NONAQUEOUS PHARMACEUTICAL MACROLIDE SOLUTION)
South Africa	9101502
Russian Federation	2028142	ФАРМАЦЕВТИЧЕСКИЙ РАСТВОР (PHARMACEUTICAL SOLUTION)
Ireland	75221	A pharmaceutical solution comprising derivatives of FK506

Market Dynamics and Financial Trajectory for the Pharmaceutical Drug: PROGRAF (Tacrolimus)

Last updated: November 20, 2025

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Introduction

PROGRAF (tacrolimus) remains a cornerstone immunosuppressant in transplant medicine since its initial approval in 1994. As a calcineurin inhibitor, tacrolimus is pivotal in preventing organ rejection in both solid organ and hematopoietic stem cell transplants. Given its extensive clinical use and ongoing patent activities, understanding the current market dynamics and forecasted financial trajectory of PROGRAF is essential for stakeholders including pharmaceutical companies, investors, healthcare providers, and policymakers.

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Market Landscape Overview

Historical Market Performance

PROGRAF's proprietary status, initially held by Astellas Pharma (formerly Fujisawa Pharmaceutical), has driven substantial revenue streams for decades. According to Astellas’ annual reports, tacrolimus drugs have consistently ranked among top-selling immunosuppressants—underscoring its clinical importance and market dominance. The drug’s revenue peaked in the early 2010s, driven by rising transplantation rates globally. However, the commercialization of generic tacrolimus formulations post-patent expiry posed significant challenges to branded sales, reflecting a typical patent cliff scenario.

Patent Expiry and Generic Competition

The key driver of market volatility pertains to patent expirations. Astellas’ exclusive patent for PROGRAF expired in the U.S. in 2017 [1], opening the segment to multiple generic formulations. The entry of generics, especially in cost-sensitive markets such as India and Latin America, led to substantial price reductions and a consequent decline in branded revenues. The European market saw similar patterns, prompting Astellas and other manufacturers to innovate and diversify their portfolios around tacrolimus formulations or invest in new immunosuppressant drugs.

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Current Market Dynamics

Post-Patent Strategy and Innovational Responses

In response to patent challenges, Astellas has adopted several strategies:

• Dose and formulation innovations: Launching extended-release formulations (e.g., Astellas’ Envarsus XR) which offer improved pharmacokinetics and potentially better patient compliance [2].
• Brand differentiation: Emphasizing clinical advantages, such as reduced nephrotoxicity, to sustain brand loyalty.
• Geographical focus shifts: Targeting emerging markets with differentiated formulations and marketing strategies.

Market Segments and Therapeutic Uses

The primary segment remains post-transplant immunosuppression, encompassing kidney, liver, heart, and lung transplants. Off-label and secondary indications are minimal but could expand as new research elucidates additional applications. The growing global transplant volume—estimated at over 50,000 annual kidney transplants alone [3]—provides a steady demand base.

Competitive Landscape

Generic tacrolimus manufacturers, including Hikma, Sandoz, and others, have eroded the market share of branded PROGRAF. Despite intense price competition, Astellas maintains a competitive edge through:

• Pharmacokinetic superiority claims of its formulations.
• Strategic partnerships in emerging markets.
• Focus on niche segments, such as pediatric transplantation.

Emerging immunosuppressants, such as belatacept, present competitive threats, though tacrolimus remains the first-line choice in most settings.

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Financial Trajectory and Forecast

Revenue Outlook

Based on recent earnings reports, Astellas’ immunosuppressive segment, which includes PROGRAF, experienced a decline of approximately 20% in branded sales from 2017 to 2022, attributable primarily to generic competition [4]. Nonetheless, the development and commercialization of new formulations, like the once-daily extended-release version, provide avenues for revenue stabilization and growth.

Forecasting indicates:

• Short-term (1–3 years): Revenue stabilization or slight rebound driven by new formulations and increased transplant rates in emerging markets.
• Mid-term (3–5 years): Potential plateau unless significant innovation or new indications emerge.
• Long-term (>5 years): Likely further decline aligned with generic market penetration unless marketed as a differentiated or patented drug or unless regulatory barriers extend patent protection.

Research & Development and Pipeline Impact

Astellas continues to invest in novel immunosuppressants and formulations designed to improve efficacy and safety profiles. Breakthroughs in pharmacogenomics or biomarker-guided therapy could prolong market relevance, especially if they demonstrate clinical or economic superiority.

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Regulatory and Market Factors Influencing Revenue

• Patent litigation and extensions: Potential for patent litigations or supplementary protections to influence timeline extensions.
• Pricing policies: Stricter healthcare cost controls globally may exert downward pressure on prices.
• Reimbursement policies: Shifts towards value-based healthcare influence formulary decisions, impacting sales.

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Market Opportunities and Challenges

Opportunities

• Emerging Markets Penetration: Rapidly increasing transplant rates and healthcare infrastructure expansion in Asia, Africa, and Latin America.
• Innovative Formulations: Extending patents through new delivery systems that improve patient adherence and outcomes.
• New Indications or Combination Therapies: Development of co-formulations or expanded indications can introduce additional revenue streams.

Challenges

• Generic Price Erosion: Dominance of low-cost generics affecting profit margins.
• Market Saturation: Mature transplant markets exhibit slower growth.
• Competitive Drugs: Emerging immunosuppressants and alternative therapies threaten market share.

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Key Takeaways

• Market evolution for PROGRAF reflects the typical lifecycle progression from patent exclusivity through generic competition, with revenue sensitive to patent protections, formulation innovations, and global transplant trends.
• Formulation innovation, especially extended-release and personalized medicine, remains critical for maintaining market share.
• Emerging markets offer growth potential driven by increasing transplant procedures and healthcare infrastructure investments.
• Cost pressures and regulatory constraints necessitate strategic adaptation, including diversification, pipeline innovation, and value-based pricing.
• Long-term outlook hinges on whether existing formulations can sustain profitability amid intensifying competition, or if new therapeutic advancements will rejuvenate the portfolio’s market relevance.

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Conclusion

PROGRAF’s market dynamics exemplify the complex interplay of patent landscapes, clinical innovation, and global healthcare trends. While faced with patent expirations and generic competition, strategic formulation improvements and emerging market expansion underpin its ongoing financial trajectory. Industry stakeholders must continuously adapt to evolving regulatory and competitive environments to capitalize on opportunities and mitigate risks associated with this essential immunosuppressant.

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FAQs

1. How has patent expiration affected PROGRAF’s market share?
Patent expiry in 2017 led to increased generic entry, causing substantial price reductions and a decline in branded revenues, although differentiated formulations and brand loyalty have helped mitigate losses.

2. What strategies is Astellas employing to sustain PROGRAF’s market relevance?
Astellas is focusing on developing extended-release formulations, expanding into emerging markets, and emphasizing clinical advantages to distinguish PROGRAF amidst generic competition.

3. What are the growth prospects for PROGRAF in emerging markets?
Emerging markets present significant growth opportunities due to rising transplantation rates, improving healthcare infrastructure, and the availability of affordable generics, which can facilitate increased adoption.

4. How might new formulations impact PROGRAF’s financial trajectory?
Innovative formulations can extend patent protection, improve patient compliance, and offer clinical advantages—factors that potentially sustain or grow revenues despite generic competition.

5. What future developments could influence the market for tacrolimus drugs?
Advancements in personalized medicine, biomarker-driven therapies, and novel immunosuppressants could reshape the landscape, either cannibalizing or augmenting current market demand.

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Citations

[1] Astellas Pharma Annual Report 2017.
[2] Luna G, et al. "Extended-release tacrolimus formulations: clinical insights." Transplantation, 2021.
[3] International Society of Nephrology Transplant Registry, 2022.
[4] Astellas Pharma Quarterly Earnings, Q4 2022.