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New Medicines

Sohonos (US)Prevention of heterotopic ossification in adults and adolescents aged ≥14 years with Fibrodysplasia Ossificans Progressiva (FOP)

Information

Sohonos (US)
New molecular entity
Ipsen
Ipsen

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Yes
Oct 22FDA requests additional information on clinical trial data that does not relate to the safety profile of palovarotene [24]
Jun 22FDA accepts NDA re-submission for priority review, with a PDUFA date of 29/12/22. Responses to questions raised by EMA have been submitted [23].
Jan 22Health Canada grant first regulatory approval of Sohonos (palovarotene capsules). Ipsen plans to make a resubmission for palovarotene in fibrodysplasia ossificans progressiva to US FDA H1 2022 and to continue the review process with the EMA after the ‘clock-stop’ period [22].
Oct 21Ipsen announce intention to re-submit NDA to US FDA H1 22; EMA have granted a clock-stop on MAA, which is likely to delay EU decision [21].
Aug 21Ipsen announces withdrawal of palovarotene NDA, confirming intention to re-submit following additional data analyses. During the review and ongoing dialogue between Ipsen and the FDA, it was recognized that additional analyses and evaluation of data collected from Ipsen’s Phase III MOVE and FOP program would be required to progress and complete the review proces and it was agreed that it would not be possible to complete this in the NDA review cycle. It is anticipated that this outcome will also trigger an EU 'clock-stop' and prolong timing of EU decision into the first half of 2022 [19, 20].
Jun 21Filed in EU via centralised procedure [18].
May 21NDA has been accepted by the U.S. FDA [17].
Feb 21Ipsen plan to submit applications to FDA and EMA H1 21 [16].
Jan 20Dosing paused in PIII and PII trials - PIII trial unlikely to meet primary endpoint [12].
Nov 19Ipsen now expect to submit NDA to FDA Q1 20 [11].
Jun 19Ipsen intend to submit NDA to FDA in second half of 2019. Palovarotene has orphan status, Fast Track, Breakthrough Therapy and Rare Pediatric Disease designations in US [10].
Oct 18Clementia intend to submit a NDA to FDA in second half of 2019 [8].
Mar 17Palovarotene has received orphan status in treatment of fibrodysplasia ossificans progressiva from the FDA and the EMA, and Fast Track status from the FDA [2].
Mar 17Clementia announce the preliminary results of the open label extension to the placebo-controlled PII trial NCT02190747. All subjects enrolled into the placebo-controlled phase (n=40) participated in the open-label extension (NCT02279095). Based on the results of the PII trials, a pivotal PIII trial programme has been developed and is expected to begin soon [1].

Category

Selective retinoic acid receptor gamma agonist; blocks heterotopic ossification
Fibrodysplasia ossificans progressiva (FOP) is an extremely rare congenital disease in which heterotopic ossification (inappropriate bone growth) occurs in voluntary muscles, often in response to local injury. It causes progressive disability and in severe cases eventual near immobility. Estimated UK incidence is 1 per 1.64 million. [3] Estimated world total number is about 2,500 of which about 700 have been confirmed; about 45 in the UK and 285 in the US [4].
Prevention of heterotopic ossification in adults and adolescents aged ≥14 years with Fibrodysplasia Ossificans Progressiva (FOP)
Oral

Further information

Yes

Trial or other data

Jan 21Estimated primary completion date of PIII NCT03312634 is now Nov 22 [15].
Mar 20Ipsen to reinitiate palovarotene dosing in patients 14 years of age and older with fibrodysplasia ossificans progressiva.The FDA partial clinical hold issued on 4 December 2019 for the pediatric population under the age of 14 for FOP and multiple osteochondroma (MO) studies remains in effect. In relation to this, Ipsen is currently addressing the questions from the FDA and other health authorities to expeditiously establish a course of action for FOP studies for the pediatric population under the age of 14.[13]
Jan 20Dosing patients has been paused in the global Phase III (PVO-1A-301) study designed to evaluate the efficacy and safety of palovarotene in patients with fibrodysplasia ossificans progressiva (FOP), as well as the ongoing Phase II (PVO-1A-202/204) extension studies [12].
Jun 19Estimated primary completion date of PIII MOVE trial November 2020 [9].
Aug 18Clementia announce recruitment to PIII MOVE trial (NCT03312634) has completed. The complany plan to complete two interim data analyses in 2019: the first when the first 35 enrolled patients have had their 12-month whole body CT (WBCT) scans (expected Q2 2019), and the second when all enrolled patients have had their 12-month WBCT scans (expected Q3/4 2019). Study results are expected in the Q4 2020 [7].
Nov 17Clementia begin recruitment to PIII MOVE trial (NCT03312634) in US. Primary efficacy endpoint is annualised change in new heterotopic ossification (HO) volume [6].
Nov 16Open label follow-up study initiated (NCT02279095) - this is intended to test various dose regimens, including a low-dose continuous treatment with short-term dose increases for eligible flare-ups. Primary outcome is percentage of flare-ups with no new HO assessed by low-dose CT scan, estimated enrolment is 58 in the US, Argentina, Australia, France and the UK, and estimated primary completion date Dec 2018 [4,5].
Oct 16Topline results released from randomised placebo controlled PII trial (NCT02190747). Participants (n=40) were aged 6 and over, had confirmed FOP, and were from the US, France and the UK. The aim of the study was to demonstrate whether palovarotene reduced heterotopic ossification (HO) following tissue flare-up and primary outcome was response measured by plain radiograph. At the end of the study period, both frequency and extent of HO were reduced in the active group vs. the placebo group [2].

Evidence based evaluations