In 2013, Sanofi was running multiple clinical trials to establish fedratinib as the cornerstone of its oncology portfolio. Then, in the space of a week, the FDA ordered a clinical hold and Sanofi canned the JAK2 inhibitor. Now, members of the team who first developed fedratinib have brought it back from the dead.
Fedratinib’s second act formally started today with a $22.5 million investment by Medicxi in Impact Biomedicines, the biotech created to rescue the cancer candidate from clinical limbo. Impact will use the cash to perform the development and manufacturing tasks that stand between fedratinib and its widespread use in myelofibrosis (MF) and polycythemia vera.
Critically, Impact has also persuaded the FDA to lift its clinical hold. The FDA made the decision after holding a Type A meeting and reviewing additional data. In doing so, the agency went some way to validating Impact’s belief the benefits of fedratinib outweigh the risks.
“There are very limited therapeutic options for these patients and fedratinib was active in most patients when nothing else had worked,” Impact CEO John Hood, Ph.D., said in a statement. “Because of the very high unmet medical need in MF, the Impact team completed a thorough review of the available data, including careful due diligence into the potential cases of WE and I am glad to report that as a result of this effort, the FDA has lifted the clinical hold.”
The FDA hit the drug with a clinical hold after learning of cases of the acute neurological condition Wernicke encephalopathy (WE). Sanofi shuttered the program days later. The Big Pharma made the decision after talks with the FDA, study investigators, neurologists and neuroradiologists led it to conclude the risks outweighed the benefits.
Hood and his collaborators saw things differently.
Sanofi reported four cases of WE in the 877 subjects who participated in 18 studies of fedratinib prior to it hitting the rocks. All the cases occurred in patients who received 500-mg doses.
Those studies included a trial in MF patients who had progressed after treatment with therapies including Incyte’s Jakafi. More than half of participants experienced spleen size reductions of 35% or more after treatment with fedratinib.
Sanofi gave up the drug in return for a stake in Impact.