CLINICAL TRIALS PROFILE FOR PALOVAROTENE

All Clinical Trials for palovarotene

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02979769 ↗	An Open-Label Extension Study of Palovarotene to Prevent Heterotopic Ossification in People With Fibrodysplasia Ossificans Progressiva (FOP) in France	Active, not recruiting	Clementia Pharmaceuticals Inc.	Phase 2	2016-11-28	Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO), i.e., abnormal bone formation, often associated with painful, recurrent episodes of soft tissue swelling (flare-ups). Lesions begin in early childhood and lead to progressive ankyloses of major joints with resultant loss of movement. In this study, the ability of different palovarotene dosing regimens to prevent the formation of new HO will be evaluated in adult and pediatric participants with FOP in France.
NCT02521792 ↗	In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects	Terminated	Clementia Pharmaceuticals Inc.	Phase 2	2015-12-07	Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation (heterotopic ossification or HO) in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor gamma (RARγ) agonists such as palovarotene to prevent HO following injury. This 36-month study will evaluate the long-term safety and efficacy of episodic treatment with palovarotene for flare-ups in FOP subjects who successfully complete two flare-up treatment periods (6 weeks duration) and two follow-up periods (6 weeks duration) in Study PVO-1A-202.
NCT02279095 ↗	An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)	Active, not recruiting	Clementia Pharmaceuticals Inc.	Phase 2	2014-10-27	Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO), i.e., abnormal bone formation, often associated with painful, recurrent episodes of soft tissue swelling (flare-ups). Lesions begin in early childhood and lead to progressive ankyloses of major joints with resultant loss of movement. In this study, the ability of different palovarotene dosing regimens to prevent the formation of new HO will be evaluated in adult and pediatric participants with FOP.
NCT02190747 ↗	An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects	Completed	Clementia Pharmaceuticals Inc.	Phase 2	2014-07-14	Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor (RAR) gamma agonists to prevent heterotopic ossification (HO) following injury. The purpose of the study is to evaluate whether palovarotene, an RAR gamma agonist, will prevent HO during and following a flare-up in subjects with FOP.

Clinical Trial Conditions for palovarotene

Condition Name

Condition Name for palovarotene
Intervention	Trials
Fibrodysplasia Ossificans Progressiva	6
Fibrodysplasia Ossificans Progressiva (FOP)	1
FOP	1
Dry Eye Disease	1

Condition MeSH

Condition MeSH for palovarotene
Intervention	Trials
Myositis Ossificans	7
Osteophyte	1
Osteochondromatosis	1
Osteochondroma	1

Clinical Trial Locations for palovarotene

Trials by Country

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−

Trials by Country for palovarotene
Location	Trials
United States	21
France	6
United Kingdom	5
Canada	4
Australia	3

Trials by US State

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−

Trials by US State for palovarotene
Location	Trials
Pennsylvania	5
California	5
Minnesota	3
Massachusetts	2
District of Columbia	1

Clinical Trial Progress for palovarotene

Clinical Trial Phase

Clinical Trial Phase for palovarotene
Clinical Trial Phase	Trials
Phase 3	2
Phase 2	5
Phase 1	3

Clinical Trial Status

Clinical Trial Status for palovarotene
Clinical Trial Phase	Trials
Completed	4
Active, not recruiting	3
Terminated	2

Clinical Trial Sponsors for palovarotene

Sponsor Name

Sponsor Name for palovarotene
Sponsor	Trials
Clementia Pharmaceuticals Inc.	9
Ipsen	2

Sponsor Type

Sponsor Type for palovarotene
Sponsor	Trials
Industry	11

Palovarotene: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to Palovarotene

Palovarotene, now approved under the brand name Sohonos, is a groundbreaking treatment for fibrodysplasia ossificans progressiva (FOP), a rare and debilitating genetic disorder. Here, we delve into the recent clinical trials, market analysis, and future projections for this critical medication.

Clinical Trials Overview

Phase 3 MOVE Trial

The pivotal Phase 3 MOVE trial was a multicenter, open-label study designed to assess the efficacy and safety of palovarotene in patients with FOP. The trial consisted of two parts: Part A, which lasted for 24 months, and Part B, a 24-month extension. Interim analyses were conducted at 12, 18, and 24 months, with the final analysis providing comprehensive data on the drug's performance[4][5].

Key Findings

The trial demonstrated that palovarotene significantly reduced the volume of new heterotopic ossification (HO) by 54% compared to untreated patients. This reduction is crucial as it slows down the progression of FOP, a disease characterized by the formation of abnormal bone in muscles, tendons, and other soft tissues[2][4].

Safety and Efficacy

Despite initial setbacks, including partial clinical holds due to safety concerns, post hoc analyses and continued trial data showed promising results. The drug was found to be effective in reducing new bone growth, although it carries risks such as premature closure of growth plates and embryo-fetal toxicity, necessitating a boxed warning[2][4].

Regulatory Journey

FDA Approval

After a tumultuous regulatory process, including a Complete Response Letter (CRL) and multiple delays, the FDA approved Sohonos in August 2023 for the treatment of FOP in females aged 8 and older and males aged 10 and older. This approval marked a significant milestone, providing the first therapy available for patients with FOP[2].

European and Canadian Regulatory Status

While the drug gained approval in Canada in 2022, it faced rejection in Europe. The European Commission's decision highlighted the varying regulatory landscapes and the challenges faced by pharmaceutical companies in securing global approvals[2].

Market Analysis

Pricing and Cost-Effectiveness

The annual cost of Sohonos is approximately $624,000 for a 5-mg daily dose, although this can vary based on disease severity and patient weight. The high cost raises questions about cost-effectiveness, with analyses suggesting that for the drug to be considered cost-effective, its price would need to be significantly reduced[2][3].

Market Potential

Given the ultra-rare nature of FOP, affecting only about 400 people in the U.S., the market for Sohonos is niche but critical. The approval of Sohonos opens up a new market segment for FOP treatments, with potential competition from Regeneron's pipeline drug expected in the future[2].

Priority Review Voucher

Ipsen's approval of Sohonos also comes with a priority review voucher, which can be sold or used to expedite future FDA applications. This voucher adds significant value to Ipsen's portfolio and can influence future market strategies[2].

Projections and Future Outlook

Patient Impact

The approval of Sohonos is a game-changer for patients with FOP, offering a treatment that can significantly improve their quality of life by reducing new bone formation. This can delay the loss of mobility and potentially extend life expectancy, which is currently around 56 years for FOP patients[2].

Competitive Landscape

While Sohonos is currently the only approved treatment for FOP, the potential entry of Regeneron's pipeline drug could introduce competition. However, Ipsen's head start and commitment to the FOP community position Sohonos as a leading treatment in this niche market[2].

Research and Development

The journey of palovarotene highlights the importance of perseverance and collaborative work between pharmaceutical companies and regulatory bodies. Future research may focus on optimizing dosing regimens, exploring other indications, and addressing the high cost of the treatment to make it more accessible to patients[2][4].

Key Takeaways

• Clinical Trials: The Phase 3 MOVE trial demonstrated palovarotene's efficacy in reducing new bone growth in FOP patients.
• Regulatory Approval: Sohonos received FDA approval in August 2023 after overcoming significant regulatory hurdles.
• Market Analysis: The drug is priced at approximately $624,000 annually, raising cost-effectiveness concerns, but it fills a critical need in the FOP treatment market.
• Future Outlook: Sohonos is expected to significantly improve patient outcomes, with potential competition from other pipeline drugs.

FAQs

What is palovarotene, and what is it used for?

Palovarotene, now approved as Sohonos, is a treatment for fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterized by the formation of abnormal bone in soft tissues.

What were the key findings of the Phase 3 MOVE trial?

The trial showed that palovarotene reduced new heterotopic ossification by 54% compared to untreated patients, significantly slowing the progression of FOP.

Why did palovarotene face regulatory delays?

Palovarotene faced delays due to safety concerns, partial clinical holds, and the need for additional data, which were eventually addressed through post hoc analyses and further submissions.

How much does Sohonos cost, and is it cost-effective?

The annual cost of Sohonos is approximately $624,000, although this can vary. For the drug to be considered cost-effective, its price would need to be significantly reduced.

What is the potential competition for Sohonos in the FOP market?

Regeneron has a pipeline drug set for FDA submission next year, which could introduce competition in the FOP treatment market.

Sources

1. Ipsen receives Complete Response Letter for palovarotene, an investigational treatment for fibrodysplasia ossificans progressiva. Ipsen.
2. After much trial and error, Ipsen scores FDA nod for Sohonos. FiercePharma.
3. Pharmacoeconomic Review - Palovarotene (Sohonos). NCBI.
4. Reduction of New Heterotopic Ossification (HO) in the Open‐Label Phase 3 MOVE Trial of Palovarotene in Patients with Fibrodysplasia Ossificans Progressiva. Journal of Bone and Mineral Research.
5. IPSEN Publishes Results of Phase III MOVE Clinical Trial. IFOPA.