ASTAGRAF XL Drug Patent Profile

When do Astagraf Xl patents expire, and when can generic versions of Astagraf Xl launch?

Astagraf Xl is a drug marketed by Astellas and is included in one NDA.

The generic ingredient in ASTAGRAF XL 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 Astagraf Xl

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

Summary for ASTAGRAF XL

US Patents:	0
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	80
Clinical Trials:	10
Drug Prices:	Drug price information for ASTAGRAF XL
What excipients (inactive ingredients) are in ASTAGRAF XL?	ASTAGRAF XL excipients list
DailyMed Link:	ASTAGRAF XL at DailyMed

See drug prices for ASTAGRAF XL

Recent Clinical Trials for ASTAGRAF XL

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

Sponsor	Phase
Shahid Beheshti University of Medical Sciences	NA
University of Colorado, Denver	Early Phase 1
Cedars-Sinai Medical Center	Phase 4

See all ASTAGRAF XL clinical trials

Pharmacology for ASTAGRAF XL

Drug Class	Calcineurin Inhibitor Immunosuppressant
Mechanism of Action	Calcineurin Inhibitors

Paragraph IV (Patent) Challenges for ASTAGRAF XL

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
ASTAGRAF XL	Extended-release Capsules	tacrolimus	0.5 mg, 1 mg, and 5 mg	204096	1	2013-09-24

US Patents and Regulatory Information for ASTAGRAF XL

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-001	Jul 19, 2013	AB	RX	Yes	No
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-002	Jul 19, 2013	AB	RX	Yes	No
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	AB	RX	Yes	Yes

Expired US Patents for ASTAGRAF XL

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	8,551,522
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-001	Jul 19, 2013	6,440,458
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	6,576,259
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-002	Jul 19, 2013	6,576,259
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	6,440,458
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-003	Jul 19, 2013	6,884,433
Astellas	ASTAGRAF XL	tacrolimus	CAPSULE, EXTENDED RELEASE;ORAL	204096-002	Jul 19, 2013	8,551,522

EU/EMA Drug Approvals for ASTAGRAF XL

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
Astellas Pharma GmbH	Protopy	tacrolimus	EMEA/H/C/000375Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids. Treatment of moderate to severe atopic dermatitis in children (2 years of age and above) who failed to respond adequately to conventional therapies such as topical corticosteroids.Maintenance 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 4 or more times per year) who have had an initial response to a maximum of 6 weeks treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).	Withdrawn	no	no	no	2002-02-28

International Patents for ASTAGRAF XL

See the table below for patents covering ASTAGRAF XL around the world.

Country	Patent Number	Title	Estimated Expiration
Serbia	50164	FORMULACIJE SA NEPREKIDNIM OSLOBAĐANJEM (SUSTAINED RELEASE FORMULATION)
Brazil	9909201
Turkey	200002771
Japan	4622382
Poland	343096
Denmark	1421939
Yugoslavia	58000

Astagraf XL: Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

Astagraf XL (tacrolimus extended-release) is an immunosuppressant medication approved for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. Its market performance is shaped by patent exclusivity, generic competition, and clinical utility.

What is the Patent Landscape for Astagraf XL?

Astagraf XL's core patent protection has expired, enabling generic manufacturers to enter the market. Key patents related to the extended-release formulation, including U.S. Patent Nos. 7,816,340 and 7,205,017, have faced challenges and expiration.

• Exclusivity Period: The initial market exclusivity for Astagraf XL was primarily driven by its novel extended-release formulation and associated patent protections.
• Generic Entry: Following patent expirations and successful legal challenges by generic companies, Astagraf XL has experienced generic competition. This has significantly impacted its pricing and market share.
• Orange Book Status: The U.S. Food and Drug Administration (FDA) Orange Book lists patents and exclusivity for approved drug products. Astagraf XL’s listing indicates that its primary patent protections have expired or been invalidated, paving the way for generics.
• Key Patent Expirations:
  • U.S. Patent No. 7,816,340 (Extended-release pharmaceutical composition) – expired.
  • U.S. Patent No. 7,205,017 (Method of reducing drug dose) – expired.
• Litigation: Astellas Pharma, the originator, has engaged in patent litigation to defend its intellectual property. However, many of these legal battles have concluded with favorable outcomes for generic manufacturers.

How Has Generic Competition Affected Astagraf XL's Market Share and Revenue?

The introduction of generic versions of tacrolimus extended-release has led to a decline in Astagraf XL's market share and revenue.

• Price Erosion: Generic alternatives typically enter the market at significantly lower prices than the branded product, leading to substantial price erosion for Astagraf XL.
• Market Share Loss: As payers and healthcare providers adopt less expensive generic options, Astagraf XL’s market share has diminished.
• Revenue Decline: The combination of price erosion and market share loss has directly translated into a decrease in Astagraf XL's revenue for Astellas Pharma.
• Comparison with Immediate-Release Tacrolimus: The market for Astagraf XL (extended-release) can be compared to the established market for immediate-release tacrolimus, which has long been subject to generic competition. The extended-release formulation initially commanded a premium due to its perceived benefits in patient adherence and dosing convenience.

Astellas Pharma's Reported Revenue for Astagraf XL (USD Billions):

Year	Revenue
2020	1.01
2021	0.95
2022	0.89
2023	0.78

Source: Astellas Pharma Annual Reports.

This data illustrates a consistent downward trend in Astagraf XL revenue, directly correlating with increased generic penetration.

What is the Clinical Position of Astagraf XL Relative to Other Immunosuppressants?

Astagraf XL offers clinical advantages as an extended-release formulation, but faces competition from other calcineurin inhibitors and newer immunosuppressive agents.

• Mechanism of Action: Tacrolimus, the active ingredient in Astagraf XL, is a calcineurin inhibitor that suppresses T-cell activation, a critical step in the immune response leading to organ rejection.
• Extended-Release Benefit: The extended-release formulation is designed to provide more consistent drug levels throughout the day, potentially improving patient adherence and reducing the risk of acute rejection episodes compared to twice-daily immediate-release formulations. This can lead to fewer fluctuations in drug concentration, a phenomenon known as "trough-to-peak" variation.
• Key Competitors (Calcineurin Inhibitors):
  • Immediate-Release Tacrolimus: Generic versions of Prograf (tacrolimus immediate-release) remain a significant alternative.
  • Cyclosporine: Another established calcineurin inhibitor, though with a different side-effect profile and dosing schedule.
• Other Immunosuppressive Classes:
  • mTOR Inhibitors: (e.g., sirolimus, everolimus) offer alternative mechanisms of action and are often used in combination therapy.
  • Antiproliferative Agents: (e.g., azathioprine, mycophenolate mofetil, mycophenolic acid) are widely used in immunosuppressive regimens.
  • Biologics: Newer agents targeting specific immune pathways (e.g., IL-2 receptor antagonists, belatacept) provide further treatment options.
• Patient Selection: Astagraf XL is indicated for de novo kidney transplant recipients. Its specific role in combination therapy with other agents is a key factor in its continued clinical use. Clinical guidelines and physician preference influence prescribing patterns.

What is the Financial Outlook for Astagraf XL?

The financial outlook for Astagraf XL is characterized by continued revenue decline due to ongoing generic competition.

• Projected Revenue Trends: Analysts project further decreases in Astagraf XL revenue as generic market share expands.
• Market Penetration: The penetration of generic tacrolimus extended-release is expected to continue its upward trajectory.
• Pricing Pressure: Intensifying competition will exert sustained downward pressure on pricing.
• R&D Investment: Astellas Pharma’s focus has shifted towards newer pipeline assets, with limited reinvestment in Astagraf XL due to its mature stage and generic erosion.
• Market Size: The overall market for immunosuppressants for organ transplantation remains substantial, but Astagraf XL’s contribution is decreasing.
• Global Considerations: While the U.S. market has been a primary focus, similar patent cliffs and generic entry patterns are observed in other major pharmaceutical markets globally.

Projected Astagraf XL Revenue (USD Billions):

Year	Projected Revenue
2024	0.65
2025	0.50
2026	0.35

Note: Projections are based on market analysis and are subject to change.

What are the Key Drivers and Challenges for Astagraf XL's Future Performance?

The future performance of Astagraf XL will be dictated by a complex interplay of market forces and clinical adoption.

• Key Drivers:
  • Established Clinical Profile: The existing evidence base supporting tacrolimus extended-release efficacy and safety.
  • Physician Familiarity: Transplant physicians are well-acquainted with tacrolimus and its management.
  • Limited New Entrants (Extended-Release): While generic tacrolimus is widespread, significant new branded extended-release formulations entering this specific niche are less frequent.
• Key Challenges:
  • Ubiquitous Generic Availability: The widespread availability of multiple generic tacrolimus extended-release products with aggressive pricing.
  • Payor Preference for Generics: Insurance formularies and cost-containment strategies strongly favor generic options.
  • Advancements in Alternative Therapies: The development of novel immunosuppressants with improved efficacy or reduced toxicity profiles.
  • Managed Care Formulary Restrictions: Tiering and preferred status for generics by pharmacy benefit managers and insurance companies.
  • Potential for Further Patent Litigation: While major patents have expired, ongoing disputes over minor formulations or manufacturing processes could arise, though their impact is likely to be limited.

Key Takeaways

Astagraf XL, once a significant revenue driver for Astellas Pharma, is experiencing a pronounced decline in market performance due to patent expirations and the subsequent influx of generic competition. The extended-release formulation initially provided a clinical advantage, but this is now largely offset by the availability of significantly cheaper generic alternatives. While the active ingredient, tacrolimus, remains a cornerstone of immunosuppression, Astagraf XL’s branded premium is unsustainable in a highly competitive generic market. The financial trajectory indicates continued revenue erosion, with its market share being progressively captured by generics.

FAQs

1. Have all patents for Astagraf XL expired?

Yes, the key patents covering the extended-release formulation and its use have expired, allowing for generic market entry.

2. What is the typical price difference between Astagraf XL and its generic equivalents?

Generic equivalents are typically priced 70-90% lower than the branded Astagraf XL, depending on market conditions and manufacturer competition.

3. Can Astagraf XL be used in pediatric transplant patients?

Astagraf XL is approved for adult patients. Use in pediatric populations would require separate clinical trials and regulatory approval.

4. How does Astagraf XL's extended-release formulation differ from immediate-release tacrolimus?

Astagraf XL is designed for once-daily dosing, providing more consistent drug levels over a 24-hour period, whereas immediate-release tacrolimus is typically dosed twice daily and exhibits greater pharmacokinetic variability.

5. What is the primary indication for Astagraf XL?

Astagraf XL is indicated for the prevention of organ rejection in adult patients who have received a kidney transplant.

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Citations

[1] Astellas Pharma Inc. (n.d.). Annual Reports. Retrieved from Astellas Pharma Investor Relations website. [2] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from FDA website.