pharma · Cystic Fibrosis · Multiple Sclerosis · RARE
Ultragenyx UK Limited
UGenDx is a pharma organization headquartered in NOVATO, CA, GB. It trades on NYSE under ticker RARE. Primary therapeutic focus areas include Cystic Fibrosis, Multiple Sclerosis, Fanconi's Anemia, Hereditary Inclusion Bo
Phase 3 · small molecule · Lymphangioleiomyomatosis
Sirolimus (brand name RAPAMUNE) is a small-molecule immunomodulating agent being developed by Ultragenyx UK Limited for lymphangioleiomyomatosis (LAM), a rare progressive lung disease. The program, identified as RDCRN 5702, is currently in Phase 3 development. Sirolimus is an established therapeutic agent with a long r
Internal code RDCRN 5702
Sirolimus (brand name RAPAMUNE) is a small-molecule immunomodulating agent being developed by Ultragenyx UK Limited for lymphangioleiomyomatosis (LAM), a rare progressive lung disease. The program, identified as RDCRN 5702, is currently in Phase 3 development. Sirolimus is an established therapeutic agent with a long regulatory history; it has been approved in multiple jurisdictions including the United States, European Union, Japan, and Australia, where it is marketed by various sponsors including Pfizer. The drug is administered topically and belongs to the antineoplastic and immunomodulating agents therapeutic class (ATC L04). Ultragenyx's Phase 3 program for LAM represents a focused development effort in a rare disease indication. The most recent milestone was recorded on 2 November 2023, indicating active program progression. The competitive landscape includes multiple immunomodulatory and anti-inflammatory agents approved for related conditions. Regulatory pathways have been established across major markets, with sirolimus holding approved status in the US (multiple ANDA and NDA approvals), EU (multiple MAH authorizations), Japan (approvals from January 2024, July 2014, and March 2018), and Australia (PBS-listed formulations). The program's completion status suggests Phase 3 data generation has concluded, positioning the program for potential regulatory submission or label expansion discussions.
Lymphangioleiomyomatosis is a rare, progressive lung disease with limited treatment options, representing a significant unmet medical need. LAM predominantly affects women of reproductive age and can lead to progressive respiratory decline and death. The disease pathophysiology involves abnormal smooth muscle cell proliferation in the lungs, lymph nodes, and kidneys. Sirolimus, as an mTOR inhibitor with immunomodulatory properties, addresses a mechanistic pathway implicated in LAM pathogenesis, offering potential disease-modifying benefits beyond symptomatic management.
Market relevance is substantial within the rare disease space, where orphan drug designations and accelerated regulatory pathways can support rapid commercialization. The patient population, though small in absolute terms, represents a high-value segment due to severity, chronicity, and limited alternatives. Ultragenyx's development strategy leverages sirolimus's established safety profile and regulatory precedent while focusing on a specific rare indication where clinical evidence of efficacy could support market differentiation.
Competitive positioning is notable given the presence of multiple immunomodulatory agents in the approved landscape (rilonacept, lenalide, pirfenidone, ponvory, and others). However, these competitors address different indications or mechanisms. Sirolimus's mTOR inhibition mechanism and topical administration route may offer distinct clinical or practical advantages in LAM management. Commercial significance is amplified by orphan drug incentives, potential for premium pricing in rare disease markets, and the possibility of label expansion into related lymphatic or smooth muscle proliferation disorders.
Drug Class: Antineoplastic and immunomodulating agent (ATC L04)
Modality: Small molecule
Route of Administration: Topical
Brand Name: RAPAMUNE
International Nonproprietary Name (INN): Sirolimus
Mechanism of Action: Not yet disclosed in the available facts; however, sirolimus is a well-characterized mTOR inhibitor with immunomodulatory and antiproliferative properties.
Target: Not yet disclosed in the available facts.
Related Therapies: Other immunomodulatory agents in the competitive landscape include rilonacept (Regeneron), lenalide (Bristol-Myers Squibb), pirfenidone (Alphapharm), ponvory (Vanda Pharmaceuticals), and luveniq (Aurinia Pharmaceuticals).
First Approval History: Sirolimus holds approved regulatory status in multiple jurisdictions. In Australia, initial listings date to June 2011 and August 2011, with a more recent listing in March 2024. In the European Union, authorizations span from 27 May 2016 to 10 April 2026 across multiple marketing authorization holders. In Japan, approvals are documented from July 2014, March 2018, and January 2024. In the United States, both originator (NDA021083, NDA021110, NDA213312, NDA213478) and generic (multiple ANDA) applications are approved.
Patent Status: Not yet disclosed in the available facts.
Also known as: lymphangioleiomyomatosis, somatic, lymphangiomyomatosis, lung lymphangioleiomyomatosis, pulmonary lymphangioleiomyomatosis, LAM
Prevalence: Point prevalence: 1-9 / 1 000 000 (Worldwide) — source: Orphanet, validated.
A multifocal neoplasm with perivascular epithelioid cell differentiation affecting almost exclusively females of child-bearing age. It is characterized by the presence of smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels. Sites of involvement include the lungs, mediastinum, and the retroperitoneum. It usually presents with chylous pleural effusion or ascites.
ClinicalTrials.gov lists 5 registered studies for Lymphangioleiomyomatosis (LAM) (AACT aggregate).
Phase breakdown: PHASE1 (2), NA (1), PHASE2 (1), PHASE3 (1)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0011705), Orphanet — lymphangioleiomyomatosis, NCT00790400, NCT02484664, NCT04388371, NCT06889168, NCT07304856, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
Phase 3 ongoing
Phase 3 clinical trial (NCT00414648) for sirolimus in lymphangioleiomyomatosis under development by Ultragenyx UK Limited.
Latest milestone recorded
Most recent program activity milestone recorded; specific milestone summary not yet disclosed.
Phase 3 completed
Program status indicates Phase 3 completion; regulatory submission or next development stage timing not yet disclosed.
The competitive landscape for immunomodulatory and anti-inflammatory therapies includes multiple approved agents across different mechanisms and indications. Rilonacept (Regeneron UK Limited) is approved and represents an alternative immunomodulatory approach. Lenalide (Bristol-Myers Squibb Australia) and pomalidomide sandoz (Lacuna Pharma) represent immunomodulatory pathways. Pirfenidone (Alphapharm, marketed as ARX-PIRFENIDONE) addresses fibrotic disease pathways. Ponvory (Vanda Pharmaceuticals) and luveniq (Aurinia Pharmaceuticals) represent distinct immunomodulatory mechanisms. Multiple generic formulations of leflunomide, teriflunomide, azathioprine, and dimethyl fumarate (Biogen, APO-DIMETHYL FUMARATE) provide additional immunosuppressive options. Alofisel (Takeda) and empaveli (Swedish Orphan Biovitrum) address specialized inflammatory and autoimmune indications. Sirolimus's competitive differentiation rests on its established mTOR inhibition mechanism, extensive regulatory precedent, favorable safety profile from decades of clinical use, and topical administration route, which may offer practical advantages over systemic alternatives in LAM management. The rare disease focus and orphan drug incentives create a distinct commercial positioning relative to broad-indication competitors.
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
United States (FDA): Sirolimus holds approved regulatory status via multiple pathways. Originator new drug applications (NDAs) include NDA021083, NDA021110, NDA213312, and NDA213478. Generic abbreviated new drug applications (ANDAs) are approved for sponsors including AADI, Alkem Labs, Amneal, Apotex, Dr Reddy's, Glenmark, Hetero Labs, MSN, Nobelpharma, Novitium Pharma, PF Prism CV, Rising, Torrent, and Zydus Pharma. Evidence available via FDA open data (open.fda.gov).
European Union (EMA): Sirolimus holds approved status with multiple marketing authorization holders (MAHs) including Pfizer Europe MA EEIG, Plusultra Pharma GmbH, and Santen Oy. EMA product numbers include EMEA/H/C/000273, EMEA/H/C/003978, and EMEA/H/C/005896. Authorization dates span 27 May 2016, 04 July 2025, and 10 April 2026. Evidence available via EMA website.
Japan (PMDA): Sirolimus holds approved regulatory status with documented approval dates of July 2014, March 2018, and January 2024. Evidence available via PMDA website.
Australia (TGA): Sirolimus is approved and PBS-listed with multiple product codes (13860L, 13885T, 13886W, 14072P, 6436R, 6437T, 6457W, 8724E, 8725F, 8833X). Sponsor names include Pfizer Australia Pty Ltd. First listed dates include 01 June 2011, 01 August 2011, and 01 March 2024. Evidence available via TGA ARTG database.
China (NMPA): Regulatory status not yet disclosed in the available facts.
Ultragenyx UK Limited Phase 3 Program (RDCRN 5702): The current Phase 3 program for lymphangioleiomyomatosis is sponsored by Ultragenyx UK Limited. Program status is listed as completed as of the latest available information. Specific regulatory pathway designation (e.g., orphan drug status, accelerated approval pathway) is not yet disclosed. Expected regulatory submission timeline and next milestone details are not yet disclosed.
Sirolimus is being developed by Ultragenyx UK Limited for lymphangioleiomyomatosis (LAM), a rare progressive lung disease characterized by abnormal smooth muscle cell proliferation.
The program (RDCRN 5702) is in Phase 3 development with completed status as of the latest available information, indicating Phase 3 data generation has concluded.
Yes, sirolimus (RAPAMUNE) is approved in the United States, European Union, Japan, and Australia for established indications, with multiple originator and generic formulations available.
Ultragenyx UK Limited is the sponsor of the Phase 3 sirolimus program for lymphangioleiomyomatosis (RDCRN 5702).
Sirolimus is an mTOR inhibitor with immunomodulatory and antiproliferative properties; specific mechanism details for the LAM program are not yet disclosed in available facts.
Sirolimus is administered topically in the formulation being developed for LAM.
The Phase 3 trial is identified as NCT00414648.
Primary endpoint specifications for NCT00414648 are not yet disclosed in the available facts.
LAM is a rare, progressive lung disease involving abnormal smooth muscle cell proliferation in the lungs, lymph nodes, and kidneys, predominantly affecting women of reproductive age.
Multiple immunomodulatory and anti-inflammatory agents are approved for related indications, including rilonacept, lenalide, pirfenidone, ponvory, and luveniq, though specific LAM-approved competitors are not detailed in the available facts.
Expected regulatory submission timeline is not yet disclosed in the available facts; the most recent milestone was recorded on 2 November 2023.
Orphan drug designation status for the LAM program is not yet disclosed in the available facts.
Sirolimus is classified as an antineoplastic and immunomodulating agent (ATC L04).
Multiple sponsors manufacture approved sirolimus formulations, including Pfizer (US, Australia, EU), Alkem Labs, Amneal, Apotex, Dr Reddy's, Glenmark, Hetero Labs, and others across different jurisdictions.
LAM predominantly affects women of reproductive age; the exact prevalence is not detailed in the available facts, but it is classified as a rare disease.
Sirolimus holds approved status in the United States (FDA), European Union (EMA), Japan (PMDA), and Australia (TGA), with multiple originator and generic approvals across jurisdictions.
Sirolimus → Drug → Target → Indication → Company → Trials → Competitors
Strategic Implications: Ultragenyx's Phase 3 completion for sirolimus in LAM represents a focused rare disease development strategy leveraging an established therapeutic agent. The topical administration route and mTOR inhibition mechanism address mechanistic pathways implicated in LAM pathophysiology. Completion of Phase 3 suggests data readiness for regulatory decision-making, positioning potential near-term catalysts for regulatory submissions or label expansion discussions.
Competitive Implications: Sirolimus enters a competitive landscape of immunomodulatory agents; however, LAM represents a specialized indication with limited approved therapies. The extensive regulatory precedent and safety database for sirolimus across multiple jurisdictions and indications may accelerate regulatory review and market access. Differentiation versus competitors hinges on clinical efficacy data from the Phase 3 trial, mechanism-specific benefits in LAM, and practical advantages of topical administration.
Future Catalysts: Key anticipated milestones include (1) Phase 3 data presentation or publication, (2) regulatory submission to FDA, EMA, PMDA, or other agencies, (3) regulatory decision (approval, conditional approval, or additional data requests), (4) potential label expansion into related lymphatic or smooth muscle proliferation disorders, and (5) commercial launch and market penetration in rare disease channels.
Expected Milestones: Specific timing for regulatory submission, approval decision, or commercial launch is not yet disclosed. The November 2023 milestone date suggests active program progression; however, expected next milestone details and timelines remain undisclosed.
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Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.