CLINICAL TRIALS PROFILE FOR ACTONEL

505(b)(2) Clinical Trials for ACTONEL

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT00632216 ↗	A Study to Determine the Satisfaction With Actonel in Postmenopausal Women With Osteoporosis	Completed	Sanofi	Phase 4	2004-05-01	The study in the labeled and real conditions of prescription of Actonel will investigate the satisfaction of patients with its new formulation: 35 mg Once A Week. The study will also measure response rates in CTX (the C-telopeptide of type I collagen) at baseline and after 12 weeks of treatment with risedronate 35 mg Once A Week.

All Clinical Trials for ACTONEL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00051636 ↗	Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period	Completed	Novartis Pharmaceuticals	Phase 3	2001-01-01	The core study looked at the effect of Zoledronic Acid given once as an intravenous (i.v.) infusion compared to 60 days of oral Risedronate in patients with Paget's disease of bone. The effect was demonstrated in the reduction of serum alkaline phosphatase (SAP). The extended observation period included participants of the core study who responded to treatment.
NCT00054418 ↗	Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer	Completed	National Cancer Institute (NCI)	Phase 3	2003-03-01	RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss. PURPOSE: This randomized phase III trial is studying two forms of calcium with or without risedronate to compare how well they work in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, stage IIIA, or stage IIIB breast cancer.
NCT00054418 ↗	Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer	Completed	Alliance for Clinical Trials in Oncology	Phase 3	2003-03-01	RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss. PURPOSE: This randomized phase III trial is studying two forms of calcium with or without risedronate to compare how well they work in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, stage IIIA, or stage IIIB breast cancer.
NCT00062595 ↗	Vitamin K and Bone Turnover in Postmenopausal Women	Completed	Eisai Co., Ltd.	Phase 3	2000-09-01	This one year study of the K vitamers phylloquinone (K1) and menatetranone (MK4) will study supplementation effects on bone turnover and bone density. Women at least 5 years postmenopause with normal bone density who do not use estrogen therapy or the following medications may be eligible: alendronate (Fosamax), risedronate (Actonel), pamidronate (Aredia), etidronate (Didronel), zoledronate (Zometa), teriparatide (Forteo), raloxifene (Evista), tamoxifene, warfarin (Coumadin), anti-seizure medications, prednisone, or oral steroids. Eligible subjects will take calcium and vitamin D (Citracal) twice a day for the first two months and through-out the study. After the first two months, subjects are randomized to the K1, MK4 or placebo groups. Return visits occur at 1, 3, 6 and 12 months. Fasting blood and urine is collected at each visit and bone density is performed at 3 study visits.

Clinical Trial Conditions for ACTONEL

Condition Name

Condition Name for ACTONEL
Intervention	Trials
Osteoporosis	12
Osteoporosis, Postmenopausal	5
Bone Loss	3
Breast Cancer	3

Condition MeSH

Condition MeSH for ACTONEL
Intervention	Trials
Osteoporosis	19
Osteoporosis, Postmenopausal	7
Bone Diseases, Metabolic	4
Breast Neoplasms	3

Clinical Trial Locations for ACTONEL

Trials by Country

Trials by Country for ACTONEL
Location	Trials
United States	72
Canada	13
Australia	5
United Kingdom	4
Spain	4

Trials by US State

Trials by US State for ACTONEL
Location	Trials
North Carolina	5
Pennsylvania	4
Ohio	4
New York	4
Massachusetts	4

Clinical Trial Progress for ACTONEL

Clinical Trial Phase

Clinical Trial Phase for ACTONEL
Clinical Trial Phase	Trials
Phase 4	16
Phase 3	12
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for ACTONEL
Clinical Trial Phase	Trials
Completed	27
Unknown status	3
Recruiting	2

Clinical Trial Sponsors for ACTONEL

Sponsor Name

Sponsor Name for ACTONEL
Sponsor	Trials
Sanofi	10
Procter and Gamble	9
University of Pittsburgh	3

Sponsor Type

Sponsor Type for ACTONEL
Sponsor	Trials
Other	32
Industry	27
NIH	5

Clinical Trials Update, Market Analysis, and Projection for Actonel

Last updated: October 28, 2025

Introduction

Actonel (risedronate sodium) is a prescription bisphosphonate primarily indicated for the treatment and prevention of osteoporosis in postmenopausal women and men, along with the management of glucocorticoid-induced osteoporosis and Paget’s disease of bone. Since its initial approval, Actonel has maintained a significant position within the osteoporosis pharmacotherapy landscape. However, evolving clinical data, market dynamics, and competitive challenges necessitate a comprehensive review of its current status and future outlook.

---

Clinical Trials Update

Ongoing and Recent Clinical Trials

Actonel’s clinical development remains active, with research focusing on expanding its therapeutic scope and optimizing treatment regimens.

• Osteoporosis and Fracture Prevention: Numerous Phase IV studies continue to evaluate long-term safety, with particular attention to atypical femoral fractures and osteonecrosis of the jaw, adverse effects associated with bisphosphonates [1].

• Paget’s Disease: Recent trials assess the efficacy of risedronate in combination therapies and alternative dosing strategies to enhance patient compliance.

• New Indications: Emerging research explores potential applications in other skeletal disorders, such as osteogenesis imperfecta and metastatic bone disease. However, no recent pivotal trials have led to approval extensions beyond existing indications.

Key Findings and Developments

• Long-term Safety Data: Extended observational data affirm the benefit-risk profile of Actonel with continued use up to 10 years, aligning with current clinical guidelines [2].

• Comparative Effectiveness: Head-to-head trials comparing Actonel with other bisphosphonates (e.g., alendronate, zoledronic acid) suggest similar efficacy but highlight differences in dosing frequency and tolerability profiles [3].

• Regulatory Interactions: The U.S. FDA and EMA have reaffirmed the safety profile of Actonel, requiring post-marketing surveillance focusing on rare adverse events rather than new warnings.

---

Market Analysis

Market Overview

The global osteoporosis market was valued at approximately USD 11.5 billion in 2022, with bisphosphonates representing a substantial share. Actonel has historically been a critical player, although its market share has declined owing to patent expiry, increasing generic competition, and evolving treatment guidelines.

Competitive Landscape

• Generic Entrants: Since patent expiration in 2012, generic versions of risedronate dominate the global market, significantly reducing branded sales revenue.

• Key Competitors: Alendronate (Fosamax), zoledronic acid (Reclast), and denosumab (Prolia) are prominent, with newer agents offering improved dosing schedules and safety profiles.

• Market Penetration: In the United States, Actonel’s market share has declined from over 25% pre-patent expiry to below 10% by 2023, primarily replaced by generics and competitors with more convenient dosing regimens (e.g., weekly vs. monthly dosing) [4].

Regional Dynamics

• North America: Leading market with high osteoporosis prevalence among aging populations; however, generic competition curtails revenue.

• Europe: Similar trends, with some markets favoring newer agents.

• Asia-Pacific: Rapid growth driven by increasing osteoporosis awareness, urbanization, and aging demographics; however, price sensitivity favors generics.

Pricing and Reimbursement Trends

Insurance coverage, especially in developed markets, remains critical. Reimbursement policies increasingly favor newer agents with better safety profiles, impacting Actonel's market share further.

---

Market Projection and Future Outlook

Short- to Mid-term Outlook (Next 5 Years)

• Market Decline but Steady Niche: Given patent expiration and new treatment options, Actonel’s revenue is expected to decrease by approximately 5-8% annually but maintain a niche following among specific patient cohorts—a population with contraindications to other bisphosphonates or where cost constraints limit access to newer drugs.

• Regulatory and Post-market Surveillance Influence: Enhanced safety monitoring may marginally influence prescribing behavior, with clinicians favoring agents with more extensive safety data or less frequent dosing.

Long-term Outlook (5–10 Years)

• Potential for Formulation Innovation: Reformulation efforts (e.g., oral formulations with improved bioavailability, new dosing schedules) could extend Actonel’s clinical utility and market lifecycle.

• Emerging Therapeutic Classes: The rise of anabolic agents like romosozumab or gene therapy approaches may further challenge bisphosphonate dominance.

• Strategic Positioning: Manufacturers could exploit niche markets, such as Paget’s disease management or in areas with limited access to newer therapies.

Impact of Regulatory Changes and Digital Health

• The integration of digital health monitoring and personalized medicine approaches may refine treatment pathways, potentially impacting the positioning of traditional bisphosphonates like Actonel.

---

Key Takeaways

1. Clinical Data Reinforces Safety and Efficacy: Long-term safety profiles remain favorable, supported by ongoing observational studies. However, rare adverse effects necessitate continued vigilance.

2. Market Decline Driven by Competition: Patent expiration and the advent of generics, coupled with newer agents offering convenient dosing and improved safety, have eroded Actonel's market share.

3. Regional Variability Presents Opportunities: Emerging markets and areas with cost constraints represent potential growth zones for generic formulations.

4. Innovation and Niche Focus are Critical: Reformulation and exploring niche indications could prolong Actonel's relevance in the osteoporosis treatment landscape.

5. Strategic Positioning and Post-marketing Surveillance are vital to sustain any remaining market presence.

---

FAQs

Q1: What are the primary reasons for the decline in Actonel’s market share?
A: Patent expiry leading to generics, competition from newer agents with better dosing convenience (weekly/monthly), and evolving safety considerations have significantly reduced its market share.

Q2: Are there ongoing clinical trials that could expand Actonel’s indications?
A: Currently, no major new trials seek to expand regulatory indications; most research focuses on long-term safety and comparative effectiveness.

Q3: How does Actonel compare with other bisphosphonates in terms of safety?
A: It has a comparable safety profile, with rare adverse events like osteonecrosis of the jaw and atypical femoral fractures, similar to other bisphosphonates.

Q4: What strategies could prolong Actonel’s market life?
A: Developing novel formulations, targeting niche indications like Paget’s disease, and leveraging regional markets with limited access to newer therapies are viable strategies.

Q5: What is the outlook for Actonel in emerging markets?
A: There is potential for growth due to cost advantages and increasing osteoporosis awareness, especially if generic versions are aggressively marketed.

---

References

1. [1] ClinicalTrials.gov. "Studies involving risedronate." https://clinicaltrials.gov.
2. [2] Black DM, et al. "Long-term safety of bisphosphonates." Journal of Bone and Mineral Research, 2021.
3. [3] Fracture Prevention Trial Groups. "Head-to-head efficacy studies of bisphosphonates." Osteoporosis International, 2020.
4. [4] MarketWatch. "Osteoporosis drug market trends and forecasts." 2022.