Sohonos (palovarotene) / Ipsen - LARVOL DELTA

Palovarotene impact on fibrodysplasia ossificans progressiva (FOP): data from month 48 of the phase III MOVE trial. (PubMed, JBMR Plus) - P=N/A, P2, P3 | "Overall, these exploratory analyses reaffirm the MOVE IA3 findings but should be interpreted with caution; potential efficacy must be weighed against the safety profile of palovarotene, particularly in growing patients. Clinical trial registration number: NCT03312634 (MOVE), NCT02322255 (NHS), and NCT02279095 (phase II OLE)."

Clinical • Journal • P3 data • Genetic Disorders

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators. (PubMed, Virulence) - "Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based in vitro systems without overt cytotoxicity at the tested concentrations. Together, this dual-reporter strategy supports efficient cross-model triage of candidate cccDNA modulators for subsequent orthogonal validation."

Journal • Preclinical • Hepatitis B • Infectious Disease • Inflammation • LOX

Long-Term Outcomes with Palovarotene in Fibrodysplasia Ossificans Progressiva: Methodology of the International, Observational, Prospective FOPal Registry (ASBMR 2026) - No abstract available

Clinical • Observational data

Flare-up Dosing with Palovarotene in Non-genetic Heterotopic Ossification (ASBMR 2026) - No abstract available

Synthesis and Reactions of Hydrazine Trifluoroborate Salts. (PubMed, Org Lett) - "In particular, we show that a wide range of pyrazole N-methylboronates can be prepared by condensation reactions with 1,3-dicarbonyl compounds and conjugated ynones with high regiocontrol. Finally, the synthetic potential of these pyrazole derivatives is demonstrated by SEAr, three-component alkyl Petasis Boron-Mannich reaction, and through the synthesis of palovarotene analogs."

Journal

Neuro-Immune Axis in Trauma-Induced Heterotopic Ossification: Mechanisms and Therapeutic Implications. (PubMed, Cells) - "Dysregulated noncoding RNAs represent promising pre-radiographic biomarkers. This neural-immune framework motivates mechanism-based therapeutic strategies targeting CGRP (fremanezumab, erenumab), SP/NK1 signaling (aprepitant), and macrophage polarization (metformin, palovarotene, rapamycin), with multi-node combination approaches tailored to the temporal stages of tHO offering the most promise for precision prophylaxis."

Journal • Review • Inflammation • Mood Disorders • RUNX2

SAME EVIDENCE, DIFFERENT DECISIONS: HOW REGULATORY STANDARDS SHAPE ORPHAN DRUG APPROVALS (ISPOR 2026) - "Three therapies with divergent outcomes were selected as case studies: palovarotene for Fibrodysplasia Ossificans Progressiva, lifileucel for advanced Melanoma, and arimoclomol for Neimann-Pick disease (type C). Variations in orphan drug regulatory outcomes reflect how regulators manage evidentiary and methodological uncertainty rather than differences in the underlying evidence. Aligning global evidence generation strategies with these regional standards is critical for mitigating pitfalls and enabling coordinated global approvals."

Frontotemporal Lobar Degeneration • Melanoma • Solid Tumor

RWE FOR SINGLE AND WELL-CONTROLLED STUDIES: AN EVALUATION OF FDA SUBMISSIONS FOR EFFECTIVENESS (ISPOR 2026) - "Examples of medicines where regulators categorized RWE as a single well-controlled study included palovarotene and tacrolimus while RWE as confirmatory included omaveloxolone, alpelisib, and pneumococcal 20-valent conjugate vaccine. While RWE use in MAAs has increased substantially, regulatory acceptability of RWE—particularly for effectiveness—has varied based on totality of evidence. Sponsors should consider the totality of evidence when incorporating RWE into MAAs."

Hematological Disorders • Infectious Disease • Pneumococcal Infections • Rare Diseases

A Study of the Blood Levels of Palovarotene in Participants With Abnormal Liver Function Compared to Healthy Adult Participants After Intake of a Single Dose (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Ipsen | Recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Feb 2026 | Trial primary completion date: Jun 2026 ➔ Feb 2026

Trial completion • Trial completion date • Trial primary completion date • Hepatology

Progressive ossification in an adolescent with fibrodysplasia ossificans progressiva. (PubMed, BMJ Case Rep) - "A biopsy was avoided due to the risk of disease exacerbation, and the diagnosis was made on clinical grounds.As no definitive cure exists, management was supportive with non-steroidal anti-inflammatory drugs for pain, nutritional supplementation and avoidance of surgery. Awareness and early recognition are crucial, while emerging therapies, such as palovarotene and gene-targeted approaches, hold promise for the future."

Journal • Fibrosis • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Pain • Pediatrics • Solid Tumor • ACVR1

Palovarotene for patients with multiple hereditary exostosis: results of MO-Ped, a terminated, randomized, placebo-controlled, double-blind phase 2 trial. (PubMed, Sci Rep) - P2 | "Interpretation of results was limited by the reduced treatment duration and smaller than expected cohort. The trial yielded important data on the natural history of MHE.Trial registration: NCT03442985 (first posted 22 February 2018)."

Clinical • Journal • P2 data • Pediatrics

FOPal: A Study to Document and to Further Describe Long-term Safety and Effectiveness of Palovarotene in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Ipsen | N=70 ➔ 100 | Trial completion date: Jan 2034 ➔ Dec 2035 | Trial primary completion date: Dec 2033 ➔ Dec 2035

Enrollment change • Trial completion date • Trial primary completion date

Fibrodysplasia Ossificans Progressiva: childhood onset from missense mutation (c.974G>C, p.G325A) in ACVR1 (AAP-NCE 2025) - "Palovarotene, a retinoid that may reduce ossification, is not yet approved for young children due to the risk of premature epiphyseal closure... This case highlights the critical need for early recognition of FOP in children with unexplained soft tissue masses and congenital skeletal anomalies. Early diagnosis facilitates genetic counseling and symptom management to slow disease progression. Continued research is necessary to clarify the role of ACVR1 variants in disease severity and management."

Clinical • Genetic Disorders • Immunology • Mood Disorders • Myositis • Orthopedics • Osteosarcoma • Sarcoma • Solid Tumor • ACVR1 • IL6 • TGFB1

A Narrative Review of Phase II and III Clinical Trials for the Pharmacological Treatment of Fibrodysplasia Ossificans Progressiva (FOP): Efficacy, Safety, and Challenges in Treatment Strategies. (PubMed, Drug Des Devel Ther) - "Promising pharmacological approaches include retinoic acid receptor γ (RARγ) agonists, such as palovarotene, and monoclonal antibodies targeting activin A, like garetosmab. Nevertheless, safety concerns and the complexities of clinical trial implementation highlight the need for innovative approaches to ensure effective and equitable treatments. Future research should prioritise long-term safety, efficacy, and patient-centred outcomes to improve FOP management."

Journal • P2 data • P3 data • Review • Genetic Disorders • Rare Diseases

Monoallelic variants in ACVR1 in a cohort of Egyptian individuals with fibrodysplasia ossificans progressiva. (PubMed, Clin Dysmorphol) - "Our study highlights the progressive nature of the disease and the importance of early diagnosis to avoid lethal complications such as locked jaw and airway obstructions that affect swallowing and breathing. An early accurate diagnosis gives an opportunity for the affected individuals in the future to be candidates for the agonist Palovarotene drug that prevents the complications arising from ectopic ossification."

Journal • ACVR1

Morpholino-Mediated Exon Skipping Targeting Human ACVR1/ALK2 for Fibrodysplasia Ossificans Progressiva. (PubMed, Methods Mol Biol) - "Here, we describe a method to reduce ACVR1 expression in FOP patient cells by exon skipping in ACVR1 mRNAs using phosphorodiamidate morpholino oligomers (PMOs). This strategy can be applied to the screen to select antisense oligomers to knockdown not only ACVR1 but also genes which cause other autosomal-dominant genetic diseases."

Journal • Genetic Disorders • Musculoskeletal Diseases • ACVR1

The first approved drug for abnormal bone formation: palovarotene challenges and way forward. (PubMed, J Pak Med Assoc) - "Given its novelty, research on palovarotene is still in its infancy. Consequently, challenges surrounding the introduction of palovarotene needs to be studied along with its potential indications and advantages in the disorders characterised by abnormal bone formation."

Journal • Immunology • Inflammation • Myositis • Orthopedics • Pain

All Restricted Spines are not Spondyloarthritis: Fibrodysplasia Ossificans Progressiva (FOP) in Monozygotic Twins presenting to Rheumatology Clinic. (PubMed, Mediterr J Rheumatol) - "The first FDA-approved drug, palovarotene, was approved in 2023...This highlights the need for awareness of this condition among both adult and paediatric rheumatologists so that harmful biopsies and surgeries can be avoided, and patients can start on newer therapies early in the disease. It can be considered a rare mimic of ankylosing spondylitis; however, the characteristic features can very well identify the disorder clinically."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Pain • Pediatrics • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis

Progressive Soft Tissue Swelling in a Pediatric Patient Leading to the Diagnosis of Fibrodysplasia Ossificans Progressiva: A Case Report. (PubMed, Pediatr Dermatol) - "The diagnostic process, which included imaging, skin biopsy, and a thorough infectious and autoimmune workup, emphasized the challenges in identifying FOP due to its rarity; however, bilateral congenital hallux valgus, often present in FOP, can be a clue for early diagnosis. While corticosteroids provide temporary relief, long-term management now includes palovarotene, a novel therapy to suppress HO."

Journal • Genetic Disorders • Immunology • Musculoskeletal Pain • Pain • Pediatrics • ACVR1

Characteristics of RWE used in Regulatory Decision-Making for Marketing Authorization Applications (MAAs) (ISPOR 2025) - " Seven medicines were analyzed: idecabtagene vicleucel (ide-cel), omburtamab, sotorasib, alpelisib, palovarotene, tacrolimus, and omaveloxolone. MAAs containing RWE submitted to the FDA were predominantly for rare diseases medicines and for first-in-class indications. Acceptability of RWE varied based on entire body of evidence. Further investigation into factors influencing RWE acceptability and its integration into MAAs across other regulators such as EMA is warranted."

Hematological Disorders • Rare Diseases

Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva. (PubMed, J Zhejiang Univ Sci B) - "Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods."

Journal • Review • Genetic Disorders • ACVR1

A Study of the Blood Levels of Palovarotene in Participants With Abnormal Liver Function Compared to Healthy Adult Participants After Intake of a Single Dose (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Ipsen

New P1 trial • Hepatology

Palovarotene in fibrodysplasia ossificans progressiva: review and perspective. (PubMed, Expert Opin Pharmacother) - "While post hoc analyses indicate that palovarotene may have modest benefits for the inhibition of new HO formation in FOP, a number of limitations and concerns remain about its generalized use. Although the long-term risks and benefits of treatment with palovarotene remain unknown, the regional approval of palovarotene marks a milestone for the FOP community at the very beginning of a new era of clinical trials."

Journal • Review • RARG

PIVOINE: A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies. (clinicaltrials.gov) - P3 | N=63 | Completed | Sponsor: Ipsen | Active, not recruiting ➔ Completed

Trial completion

FOPal: A Study to Document and to Further Describe Long-term Safety and Effectiveness of Palovarotene in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (clinicaltrials.gov) - P=N/A | N=70 | Recruiting | Sponsor: Ipsen | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2035 ➔ Jan 2034 | Trial primary completion date: Dec 2035 ➔ Dec 2033

Enrollment open • Trial completion date • Trial primary completion date