This press release has been approved by ASBMR for distribution on 25 August

• Post hoc analyses showed substantial reduction (62%) in mean annualized new heterotopic ossification volume in patients with FOP who were treated with oral investigational therapy palovarotene¹
• Results from the third interim analysis of the MOVE trial, the first and only multicenter Phase III study of its kind, comprising the largest interventional study in FOP to date with 107 participants, suggest that palovarotene may be an important therapeutic option in FOP¹

 

PARIS, FRANCE, 25 August 2020 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced results from the MOVE trial, the first and only multicenter Phase III study in fibrodysplasia ossificans progressiva (FOP), to be presented during an oral presentation at the American Society for Bone and Mineral Research (ASBMR) 2020 annual meeting (Saturday, 12 September, 11:00am – 12:30pm ET). Dosing of palovarotene in the MOVE clinical trial was paused when futility criteria were met at a pre-specified interim analysis. However, subsequent post hoc analyses showed the RARy agonist oral investigational therapy palovarotene reduced mean annualized new heterotopic ossification (HO) volume in pediatric and adult participants with FOP. This was compared with untreated patients from a natural history study over 24 months.¹

Results from the MOVE trial demonstrated a 62% reduction in mean annualized new HO volume in participants treated with palovarotene (8,821 mm³) (n=97) versus untreated (23,318 mm³) (n=98) patients (nominal weighted linear mixed effects [wLME] model est. –11,611mm³, p-value = 0.0292). Premature physeal closure (PPC) (n=18) or epiphyseal disorder (n=1) was observed in 27.1% (19/70) of participants who were skeletally immature at baseline.¹ Palovarotene safety data were otherwise generally consistent with the known adverse event (AE) profile of retinoids.

FOP is an ultra-rare, genetic disorder that affects approximately 1.36 per million individuals worldwide^2,3 and is characterized by formation of bone in soft and connective tissues, known as HO.⁴ Sporadic episodes of painful soft tissue swelling, called “flare-ups”, can precede HO.³ HO is permanent and leads to severe functional limitations in joint mobility, progressive and cumulative disability and to shortened life expectancy. There are currently no approved treatments for the reduction or prevention of heterotopic bone formation in FOP.⁴

“Accumulation of HO across the body is the defining characteristic of FOP and severely limits physical function over time,” said Dr Robert Pignolo, M.D., Ph.D., Division of Geriatric Medicine and Gerontology, Department of Internal Medicine, Mayo Clinic. “The MOVE trial provides important insight into long-awaited treatment strategies and demonstrates that the oral therapy palovarotene can reduce new HO volume, representing an important therapeutic option in FOP especially in older children and adults.”

“We are pleased to present the third interim analysis results of the Phase III MOVE trial in FOP, evaluating Ipsen’s oral investigational therapy palovarotene, to the global community at the ASBMR annual meeting,” said Jim Roach, M.D., Senior Vice President and Global Head of Rare Diseases Therapeutic Area at Ipsen. “Based on preliminary discussions with the FDA, Ipsen’s intent is to move forward with an NDA submission and discussions with the EMA are ongoing. We remain committed to working with regulators and are delighted to be one step closer to our goal of bringing this potential treatment option to people living with FOP in a timely manner.”

“People living with FOP face life-threatening challenges with limited treatment options. We are encouraged by these data showing a reduction in HO volume from the MOVE trial, which hopefully will result in a new potential treatment option for the FOP community,” said Adam Sherman of the International Fibrodysplasia Ossificans Progressiva Association (IFOPA).

MOVE (NCT03312634) is an ongoing Phase III, multicenter, open-label trial of 107 patients with FOP who received oral palovarotene as a chronic (5mg once daily) and episodic (20mg once daily for 4 weeks, followed by 10mg for ≥8 weeks for flare-ups and trauma) regimen. The primary objectives of the MOVE trial are to evaluate the efficacy of palovarotene in reducing new HO volume in patients with FOP as assessed by low-dose, whole body computed tomography (WBCT, excluding head) compared with untreated patients from Ipsen’s global FOP natural history study (NHS; NCT02322255), and to evaluate the safety of palovarotene in adult and pediatric patients with FOP.⁵ The NHS is a first-of-its kind study into the evaluation of FOP disease progression. In June, Ipsen presented 8 abstracts in the Journal of Endocrine Society as part of our ongoing commitment to rare diseases. The data included an abstract highlighting 12-month data on the natural progression of FOP and the impact of HO on patients’ physical functioning over time from the NHS study.⁶

At data cut off, all study participants had reported ≥1 treatment-emergent adverse event (TEAE); 97.0% reported ≥1 retinoid-associated TEAE (e.g. mucocutaneous events). Maximum AE severity was mild in 32.2% of participants, moderate in 45.5%, and severe in 22.2%. Premature physeal closure (PPC) (n=18) or epiphyseal disorder (n=1) was observed in 27.1% (19/70) of participants who were skeletally immature at baseline.¹ Results demonstrated a 62% reduction in mean annualized new HO volume in participants dosed with palovarotene (8,821 mm³) versus untreated (23,318 mm³) patients (nominal wLME model p-value = 0.0292). The data presented on 12 September are from the third interim analysis (IA3) of MOVE.