RAPAMUNE Drug Patent Profile

When do Rapamune patents expire, and what generic alternatives are available?

Rapamune is a drug marketed by Pf Prism Cv and is included in two NDAs.

The generic ingredient in RAPAMUNE is sirolimus. There are twenty-one drug master file entries for this compound. Twenty suppliers are listed for this compound. Additional details are available on the sirolimus profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Rapamune

A generic version of RAPAMUNE was approved as sirolimus by ZYDUS PHARMS on January 8^th, 2014.

Summary for RAPAMUNE

US Patents:	0
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	2
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	233
Patent Applications:	3,499
Drug Prices:	Drug price information for RAPAMUNE
What excipients (inactive ingredients) are in RAPAMUNE?	RAPAMUNE excipients list
DailyMed Link:	RAPAMUNE at DailyMed

See drug prices for RAPAMUNE

Recent Clinical Trials for RAPAMUNE

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

Sponsor	Phase
Stanford University	Phase 1/Phase 2
Markus Mapara	Phase 1/Phase 2
ITB-Med LLC	Phase 1/Phase 2

See all RAPAMUNE clinical trials

Pharmacology for RAPAMUNE

Drug Class	Kinase Inhibitor mTOR Inhibitor Immunosuppressant
Mechanism of Action	Protein Kinase Inhibitors mTOR Inhibitors
Physiological Effect	Decreased Immunologic Activity

Paragraph IV (Patent) Challenges for RAPAMUNE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
RAPAMUNE	Tablets	sirolimus	0.5 mg	021110	1	2010-09-28
RAPAMUNE	Tablets	sirolimus	1 mg and 2 mg	021110	1	2009-12-17

US Patents and Regulatory Information for RAPAMUNE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Pf Prism Cv	RAPAMUNE	sirolimus	SOLUTION;ORAL	021083-001	Sep 15, 1999	AA	RX	Yes	Yes
Pf Prism Cv	RAPAMUNE	sirolimus	TABLET;ORAL	021110-002	Aug 22, 2002	AB	RX	Yes	Yes
Pf Prism Cv	RAPAMUNE	sirolimus	TABLET;ORAL	021110-004	Jan 25, 2010	AB	RX	Yes	No

Expired US Patents for RAPAMUNE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Pf Prism Cv	RAPAMUNE	sirolimus	TABLET;ORAL	021110-004	Jan 25, 2010
Pf Prism Cv	RAPAMUNE	sirolimus	TABLET;ORAL	021110-001	Aug 25, 2000
Pf Prism Cv	RAPAMUNE	sirolimus	TABLET;ORAL	021110-001	Aug 25, 2000

EU/EMA Drug Approvals for RAPAMUNE

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Pfizer Europe MA EEIG	Rapamune	sirolimus	EMEA/H/C/000273Rapamune is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving a renal transplant. It is recommended that Rapamune be used initially in combination with ciclosporin microemulsion and corticosteroids for 2 to 3 months. Rapamune may be continued as maintenance therapy with corticosteroids only if ciclosporin microemulsion can be progressively discontinued., , Rapamune is indicated for the treatment of patients with sporadic lymphangioleiomyomatosis with moderate lung disease or declining lung function.,	Authorised	no	no	no	2001-03-13
Plusultra pharma GmbH	Hyftor	sirolimus	EMEA/H/C/005896Hyftor is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis complex in adults and paediatric patients aged 6 years and older.	Authorised	no	no	yes	2023-05-15

International Patents for RAPAMUNE

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

Country	Patent Number	Title	Estimated Expiration
Australia	1014592
Canada	2059432	NANOPARTICULES DE MEDICAMENT MODIFIE EN SURFACE (SURFACE MODIFIED DRUG NANOPARTICLES)
Israel	94634	Compositions inhibiting transplant rejection in mammals using rapamycin and a chemotherapeutic agent

Supplementary Protection Certificates for RAPAMUNE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0648494	01C0037	France		PRODUCT NAME: SIROLIMUS; NAT. REGISTRATION NO/DATE: EU/1/01/171/001-005 20010313; FIRST REGISTRATION: IKS55243 20000926
0648494	C300055	Netherlands		PRODUCT NAME: SIROLIMUS, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AAN- VAARDBAAR ZOUT; NATL. REGISTRATION NO/DATE: EU/1/01/171/001 - EU/1/01/171/005 20010313; FIRST REGISTRATION: CH CH/55243 20000926
0763039	SPC/GB08/025	United Kingdom		PRODUCT NAME: TEMSIROLIMUS AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF; REGISTERED: UK EU/1/07/424/001 20071119

Market Dynamics and Financial Trajectory for RAPAMUNE (Sirolimus)

Last updated: July 28, 2025

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Introduction

RAPAMUNE, the brand name for sirolimus, is an immunosuppressant drug predominantly used to prevent organ transplant rejection and treat certain rare diseases. Since its initial approval in 1999 for renal transplantation, RAPAMUNE's market trajectory has experienced significant shifts driven by clinical developments, regulatory changes, and evolving healthcare landscapes. This detailed analysis explores the current market dynamics and forecasts the financial trajectory of RAPAMUNE within a complex, competitive environment.

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Pharmacological Profile and Clinical Applications

RAPAMUNE is a macrocyclic lactone that inhibits the mammalian target of rapamycin (mTOR). It primarily functions as an immunosuppressant, suppressing T-cell proliferation, thereby reducing the risk of transplant rejection. Its approved indications have expanded over time, notably including treatment-resistant lymphangioleiomyomatosis (LAM) and off-label use in certain cancers.

The drug's core application remains in solid organ transplantation, especially kidney transplantation, where it is often used either as a primary immunosuppressant or as part of combination therapy. Its utility in drug-eluting stents and potential anti-proliferative effects further diversify its clinical portfolio.

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Market Dynamics Influencing RAPAMUNE

1. Competitive Landscape and Market Share Shifts

RAPAMUNE competes mainly with other immunosuppressants such as tacrolimus, mycophenolate mofetil, and corticosteroids. The proliferation of generic versions following patent expiry significantly impacted its market dominance. Notably, the loss of exclusivity in several regions reduced prices, affecting revenue streams.

Biologics and newer agents like belatacept are gradually encroaching upon the market, offering alternative immunosuppressive mechanisms with potentially improved safety profiles, such as reduced nephrotoxicity—challenging RAPAMUNE's market position.

2. Regulatory and Patent Developments

Patent expirations, primarily in developed markets around 2013-2015, triggered a wave of generic entry, leading to substantial price reductions. Regulatory approvals for expanded indications—like LAM—have provided new revenue streams, offsetting some losses. However, patent laws and exclusivity periods vary regionally, affecting global market dynamics.

3. Price Trends and Reimbursement Policies

Price erosion due to generic competition has exerted downward pressure on revenues. Reimbursement policies increasingly favor cost-effective alternatives, further constraining RAPAMUNE's market share. While some healthcare systems continue to reimburse branded products favorably, broader economic pressures incentivize clinicians to opt for generics.

4. Clinical and Pharmacovigilance Challenges

Long-term safety concerns, such as increased risks of hyperlipidemia, infections, and certain malignancies, influence prescribing behaviors. Growing evidence favoring newer immunosuppressants with improved safety profiles can hinder RAPAMUNE's growth prospects.

5. Emerging Indications and Research

Ongoing clinical trials investigating RAPAMUNE for oncology, dermatology, and other immune-mediated diseases potentially open new markets. Nonetheless, regulatory approval for such indications remains uncertain, and commercial viability hinges upon demonstration of distinct advantages over existing therapies.

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Financial Trajectory Forecast

Historical Performance:

Between 2010 and 2015, RAPAMUNE's revenues peaked, buoyed by high institutional demand post-patent expiry, with annual revenues reaching approximately $500 million globally. Post-2015, a decline ensued due to generic competition, with revenues decreasing by an estimated 10-15% annually, reflecting pricing pressure and shifting prescriber preferences.

Current Status and Trends:

By 2023, global sales have stabilized around $250-300 million, with North America accounting for the bulk due to higher transplantation rates and reimbursement policies. The market remains segmented, with hospitals, transplant centers, and specialty pharmacies as key distribution channels.

Forecast (2023-2030):

Projections suggest a continued gradual decline in RAPAMUNE revenues, approximating a 3-5% compound annual decline, driven by:

• Market Saturation in Major Regions: Burned-out demand in mature markets.
• Emerging Competition: The rise of biologics with better safety profiles and convenience, such as belatacept, which could further erode RAPAMUNE's share.
• Pricing Pressures: Generics and biosimilars entering markets at lower prices.
• Limited Pipeline for New Indications: While exploratory research persists, significant revenue-driving approvals are unlikely before mid-decade.

However, potential growth avenues include:

• Expansion into Rare Indications (e.g., LAM): Provided regulatory hurdles are cleared.
• Partnerships and Licensing Agreements: To facilitate access in emerging markets.
• Combination Therapies: Incorporating RAPAMUNE with novel agents to improve safety and efficacy profiles.

Long-term prospects appear modest, with a possible plateauing or further decline in global sales unless innovative applications or formulation improvements materialize.

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Market Drivers and Barriers

Drivers:

• Ongoing need for effective immunosuppressants.
• Clinical evidence supporting RAPAMUNE's efficacy.
• Expansion into new indications can open fresh revenue streams.
• Growing transplantation procedures globally.

Barriers:

• Price erosion and loss of patent exclusivity.
• Competition from newer agents and biosimilars.
• Safety concerns and adverse effect profiles.
• Regulatory delays in approving new indications.

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Regulatory and Industry Outlook

The industry trend favors personalized medicine and safer immunosuppressive regimens. Regulatory agencies are increasingly scrutinizing long-term safety, influencing the development and marketing strategies for RAPAMUNE. The advent of biosimilars and generics emphasizes the importance of competitive pricing and alternative value propositions.

Strategic collaborations, like licensing or co-marketing agreements, could help extend RAPAMUNE’s financial relevance, especially in emerging markets where affordability and access are critical.

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Key Takeaways

• RAPAMUNE's market peak occurred in the early 2010s, buoyed initially by transplant needs and expanded indications.
• Patent expirations significantly reduced revenues, with generic competitors driving prices downward.
• A challenging competitive environment persists, with biologics and newer agents gaining traction.
• Revenue projections indicate a continued modest decline, with alternative growth avenues limited but possible via new indications.
• The drug's future depends on innovative clinical research, strategic partnerships, and adapting to evolving regulatory and market landscapes.

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FAQs

1. How has patent expiry affected RAPAMUNE's market share?
Patent expiry led to the entry of generics, drastically reducing prices and market share, especially in North America and Europe, where cost competition intensified.

2. What are the main competitors to RAPAMUNE in immunosuppressive therapy?
Main competitors include tacrolimus (also facing generic competition), mycophenolate mofetil, belatacept, and other biologic agents offering alternative immunosuppressive mechanisms with potentially better safety profiles.

3. Are there new therapeutic indications that could revive RAPAMUNE’s market?
Potential expansion into rare diseases like lymphangioleiomyomatosis and certain cancers through clinical trials could create new markets, though regulatory and clinical validation remain hurdles.

4. How does safety profile impact RAPAMUNE’s adoption?
Long-term safety concerns, such as metabolic disturbances and infection risks, negatively influence clinician preferences, favoring drugs with improved safety profiles.

5. What strategic actions can enhance RAPAMUNE’s market position?
Forming licensing agreements, expanding into emerging markets, and investing in clinical trials for new indications or improved formulations are vital strategies for maintaining relevance.

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References

[1] U.S. Food and Drug Administration (FDA). RAPAMUNE (Sirolimus) Drug Label. 1999.
[2] MarketsandMarkets. Immunosuppressants Market by Drug Type, Indication, and Region. 2022.
[3] EvaluatePharma. World Preview 2023: Outlook to 2028.
[4] European Medicines Agency (EMA). Summary of Product Characteristics for Rapamune.
[5] Grand View Research. Global Transplant Market Insights. 2022.