FDA Grants Approval to Ipsen’s Sohonos Capsules, the First-Ever Treatment for Individuals with Fibrodysplasia Ossificans Progressiva

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Ipsen, Clementia, FDA, Roche, Pharma, rare diseases, FDA approval, Sohonos

In 2019, Ipsen made a significant investment of $1 billion to acquire Clementia Pharmaceuticals and its rare disease drug, palovarotene. The drug was deemed a relatively safe bet at the time. However, over the next four years, the journey to FDA approval proved tumultuous, marked by clinical trial holds, setbacks, safety concerns, and regulatory rejections.

After overcoming multiple obstacles, Ipsen has finally received FDA approval for their drug, now named Sohonos. This breakthrough marks a pivotal moment as it offers the first-ever therapy for fibrodysplasia ossificans progressiva (FOP), an ultra-rare bone disease that severely restricts mobility and shortens life expectancy. FOP affects around 400 individuals in the U.S. and is characterized by abnormal bone growth that immobilizes patients, often leading to respiratory failure and early death.

Sohonos, an oral medication, works by curbing the abnormal bone growth through its retinoic acid receptor gamma agonist mechanism. Clinical trials demonstrated a 54% reduction in new bone growth, providing hope for those suffering from this devastating disease. Despite this success, caution is advised, particularly in children, due to potential risks like premature closure of growth plates and embryo-fetal toxicity, which are outlined in the medication’s boxed warning.

Ipsen plans to price Sohonos at $624,000 annually for a 5-mg daily dose, with variations based on disease severity and patient weight. While Ipsen is at the forefront now, competition from Regeneron could emerge, as their pipeline drug is poised for an FDA submission next year.

Ipsen could potentially encounter competition from Regeneron in this therapeutic field, as the latter is preparing for an FDA submission of their pipeline drug next year.

Upon receiving approval, Ipsen gains possession of a priority review voucher, offering the flexibility to either sell it or expedite future FDA applications. The developmental journey of palovarotene is intriguing; originally developed by Roche, the worldwide rights were sold to Clementia in 2013 after disappointing results in a Phase II emphysema trial. Palovarotene’s fortunes shifted when a Phase II trial focusing on FOP paved the way for its eventual FDA submission in 2019.

โ€œAs a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with. The published Phase III MOVE study showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP. Sohonos is not for everyone. As with all medicines there are risks in this case especially for young children who may develop early growth plate closure. In addition, Sohonos has the same side effects as other retinoids, including dryness of the skin and mucus membranes. However, since the accumulation of HO in FOP is progressive, irreversible, and life altering, this medication is an important treatment option for our FOP community.โ€

– Dr Edward Hsiao, Professor of Medicine, Division of Endocrinology and Metabolism, University of California, San Francisco

However, following Ipsen’s acquisition of Clementia, the FDA placed two clinical trials for palovarotene on partial hold due to safety concerns. The situation worsened in early 2020 when an interim analysis suggested the Phase III FOP trial might not meet its primary endpoint. Subsequently, a pivotal trial in another potentially lucrative area was abandoned, attributing the decision to potential data integrity issues stemming from the clinical hold. This series of setbacks resulted in Ipsen recording a substantial 669 million euro impairment charge.

โ€œThe FDA approval of Sohonos is a breakthrough for the U.S. FOP community. For the first time doctors have an approved medicine available to them, shown to reduce the formation of new, abnormal bone growth, known as heterotopic ossification (HO), which causes debilitating mobility challenges and has a devastating impact on the lives of people with FOP. Development of medicines for rare diseases takes commitment and belief from everyone involved. We at Ipsen are sincerely grateful to the FOP community of patients and medical experts, as the first-ever treatment in the U.S. for managing FOP would not be possible without their participation in the clinical trials and ongoing support.โ€

– Howard Mayer, Head of Research and Development, Ipsen

Nonetheless, post hoc analysis within the FOP trial revealed a potential path to approval. This revised approach secured approval from Canadian regulators in 2022, but unfortunately received a final rejection in Europe last month.

In 2022, the FDA had planned an advisory committee meeting to discuss palovarotene but canceled it, requesting additional data from Ipsen. The regulator rejected Ipsen’s application for approval two months later. However, in early 2023, Ipsen provided the necessary data, leading to a comprehensive advisory committee meeting in June, resulting in a favourable 10-4 vote for approval.

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