The curse of palovarotene continues. After struggling through a series of setbacks, Ipsen filed for FDA approval of the rare disease drug earlier this year, moving it a step closer to realizing some return on its $1 billion bet on the asset. Now, Ipsen has pulled the filing.
Ipsen withdrew the submission after talks with the FDA led it to identify the need for “additional analyses and evaluation of data.” The extra work will take too long to fit into the review cycle, forcing Ipsen to pull the submission and ending hopes of bringing palovarotene to market this year. Shares in Ipsen fell 12% in early trading in Paris, sliding from €92 ($108) to €81 as investors digested the news.
Paris-based Ipsen plans to refile for approval after completing the additional data analyses. The fact that Ipsen is analyzing existing data, rather than generating new results, points to a relatively short delay, but the company is yet to commit to a timeline. Analysts at Jefferies set out their take on the implications of the withdrawal in a note to investors.
“Assuming the analyses take a few months to complete, Ipsen could potentially re-file in the U.S. during 4Q21E, in our view. This could then allow for potential approval around mid-22E assuming FDA again grants Priority Review, albeit this could be expedited given the FDA is already familiar with the file. We also expect this outcome to trigger an EU ‘clock-stop’ and prolong timing of the EU decision into 1H22E,” the analysts wrote.
The withdrawal is yet another blow to the palovarotene program. When Ipsen acquired palovarotene in its takeover of Clementia Pharmaceuticals early in 2019, its then CEO David Meek called the asset “largely derisked.” That assessment proved to be wildly optimistic.
By the end of 2019, the FDA had put two clinical trials of palovarotene on partial clinical hold after seeing a safety signal in children taking the retinoic acid receptor gamma agonist. The situation went from bad to worse in the first quarter of 2020, when an interim analysis found a phase 3 clinical trial was unlikely to meet its primary endpoint.
Two months later, Ipsen scrapped a pivotal trial in a second, potentially more lucrative indication as the pause in dosing imposed by partial clinical hold may have compromised the integrity of the data. Between the two clinical setbacks, Ipsen recorded a €669 million partial impairment.
Despite suffering a succession of blows, Ipsen continued trying to find a path forward. The trial that was deemed unlikely to meet its primary endpoint kept going, and Ipsen did post hoc analyses that, in its words, uncovered “encouraging therapeutic activity.”
The interim analysis pointed to the inability of palovarotene to stop new bone formation outside of the normal skeletal system, the defining characteristic of fibrodysplasia ossificans progressiva (FOP) and the primary endpoint of the pivotal study. Yet, the post hoc analyses linked palovarotene to a 62% drop in the mean annualized formation of new bone outside of the skeletal system.
Ipsen used the post hoc analyses to file with the FDA, securing a priority review that positioned it to learn whether the agency would approve the drug by the end of November. The need for more analyses means the wait for a new treatment for patients with FOP, a disease that leads to loss of mobility and shortened life expectancy, will continue into 2022.