IPSEN

Regulatory News:

Ipsen (Euronext: IPN; ADR: IPSEY) announced today it will begin to reinitiate palovarotene dosing in patients 14 years of age and older currently participating in its fibrodysplasia ossificans progressiva (FOP) clinical program. The Food and Drug Administration (FDA) in the U.S. has confirmed they have no safety concerns with restarting dosing in patients 14 years of age and older. Clearance to reinitiate dosing in these patients has also been received to date from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK, the National Agency for the Safety of Medicines and Health Products Safety (ANSM) in France, the Medical Products Agency (MPA) in Sweden, the Italian Medicines Agency (AIFA), the National Administration of Drugs, Foods, and Medical Devices (ANMAT) in Argentina, the Spanish Agency of Medicines and Medical Devices (AEMPS), and Health Canada (HC).

The decision to pause dosing of palovarotene in the global Phase III MOVE trial (PVO-1A-301), as well as the ongoing Phase II (PVO-1A-202/204) extension studies in FOP was made by Ipsen on 24 January 2020, based on results of a futility analysis as part of the pre-specified interim analysis.

Encouraging therapeutic activity was observed in preliminary post-hoc analyses of interim data for the Phase III MOVE trial and shared with, and acknowledged by, the Independent Data Monitoring Committee (IDMC). As such, the company amended the protocol for the Phase III MOVE trial to include updates to the statistical analysis section as recommended by the IDMC to allow for additional analyses to be performed in addition to the primary pre-specified analysis. The protocol amendments are based on the IDMC’s observation that the protocol pre-specified statistical model may have negatively affected the efficacy analysis and shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment.

“We are pleased that Ipsen has received the approval to reinitiate dosing in patients 14 years of age and older in the Phase III MOVE trial from several regulatory agencies to date following review of the additional data. After consultation with patient groups and investigators, we have been working diligently with all relevant stakeholders to restart the trial as quickly as possible,” said Dr. Howard Mayer, Executive Vice President and Head of Research and Development at Ipsen. “We remain committed to bringing palovarotene to patients living with this devastating disease and will continue our conversations with the health authorities to determine the most appropriate regulatory path forward.”

Ipsen is now working to obtain the approvals from the ethics committee (EC) of each clinical site and, upon receipt of both regulatory approval where required and EC approval, the reinitiation of dosing may begin. At this point, physicians or trial coordinators will contact eligible patients to share more details and advise on appropriate steps for the reinitiation of treatment. Appropriate measures will also be taken to ensure the safety of FOP patients who restart dosing in light of the ongoing COVID-19 pandemic, taking into consideration local regulatory and health authority guidance, as well as the ability of individual investigators and sites to adequately monitor patient safety.

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.

Ipsen is also addressing the partial clinical hold questions from the FDA related to the MO program. However, Ipsen has taken the decision to terminate its MO-Ped trial (PVO-2A-201) conducted under IND135403 to analyze the accumulated data to better inform on the efficacy, safety and future of palovarotene in MO, and to potentially establish a path forward for palovarotene in this indication, including an assessment as to the potential for an NDA submission to the FDA. Ipsen believes however that an NDA submission for the treatment of MO based on the MO-Ped trial (PVO-2A-201) conducted under IND135403 is highly unlikely. The reasons for Ipsen’s decision include the time that the partial clinical hold has been in place leading to a significant gap in dosing which may compromise the integrity of the data, that the trial was not fully enrolled at the time the partial clinical hold was instituted (as such, very few patients had reached the trial midpoint), and there is no efficacy data available in this patient population currently to further inform a benefit/risk assessment.

About the FOP clinical program
The Phase III MOVE (PVO-1A-301) trial is an open-label, single-arm, efficacy and safety trial evaluating a chronic/episodic dosing regimen of palovarotene which includes a 5 mg daily dose of palovarotene in addition to the episodic 20/10 mg dosing regimen following any flare-ups (note that doses are weight-adjusted). The trial is being conducted in the U.S., Argentina, Australia, Brazil, Canada, France, Italy, Japan, Spain, Sweden and the United Kingdom. There are two ongoing Phase II (PVO-1A-202/204) extension studies; 1) Study 202 an open-label extension of Study 201, the initial Phase II randomized, double-blind, multi-center trial, and 2) Study 204 an open-label study corresponding to PVO-1A-202 to evaluate the safety and efficacy of different palovarotene dosing regimens in subjects with FOP in France.

About palovarotene
Palovarotene is a RARγ agonist being developed as a potential treatment for patients with ultra-rare and debilitating bone diseases, including fibrodysplasia ossificans progressiva (FOP) and multiple osteochondromas (MO), as well as other conditions including dry eye disease. Palovarotene, which had rare pediatric disease and breakthrough therapy designations for the treatment of an ultra-rare bone disorder, was acquired by Ipsen through the acquisition in April 2019 of Clementia Pharmaceuticals.

About fibrodysplasia ossificans progressiva (FOP)
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling disorder characterized by bone that forms outside the normal skeleton, in muscles, tendons or soft tissue.¹ FOP is among the rarest of human diseases, and while there are approximately 1,000 confirmed cases globally, the prevalence of FOP is estimated at approximately 1.36 per million individuals.^2,3

About Ipsen
Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and Specialty Care. The Group develops and commercializes innovative medicines in three key therapeutic areas – Oncology, Neuroscience and Rare Diseases. Its commitment to oncology is exemplified through its growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales over €2.5 billion in 2019, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial presence in more than 30 countries. Ipsen’s R&D is focused on its innovative and differentiated technological platforms located in the heart of the leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,800 employees worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com .

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References

1. The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations, IFOPA. Accessed: March 2020. Available: http://fundacionfop.org.ar/wp-content/uploads/2019/05/GUIDELINES-May-2019.pdf
2. Lilijesthrom M & Bogard B. FOP Drug Development Forum. Boston, MA; 2016.
3. Baujat et al. Orphanet Journal of Rare Diseases (2017) 12:123.

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