Last week’s US approval of fedratinib for myelofibrosis, a project that Celgene bought for an initial $1.1bn in early 2018, provides validation of sorts for the big biotech’s much-maligned business development track record. However, a closer look at the Jak 2 inhibitor, now branded Inrebic, shows why the company deserves some of the criticism. Inrebic has a black box warning for encephalopathy, including Wernicke’s, a signal that was well appreciated at the time of the Celgene buyout; hepatic and gastrointestinal toxicities also differentiate Inrebic from Jakafi, the blockbuster Jak 1/2 inhibitor from Incyte and Novartis that dominates the myelofibrosis space. Jakafi carries its own concerns but Inrebic’s toxicity profile will surely restrict its use; comparing the two agents’ efficacy data, with all the usual caveats, only reinforces this image. Myelofibrosis might be underserved – and not all patients respond to Jakafi – but ending up with a second-line agent was presumably not Celgene’s intention. It is therefore hard to see how the top-dollar up-front fee, and $1.4bn due in regulatory milestones, will be recouped. Consensus from EvaluatePharma has sales of $378m by 2024, a figure that could well be trimmed once analysts take a fresh look at Inrebic’s prospects.
|Cross trial comparison of Jakafi and Inrebic|
|Inrebic – Jakarta study||Jakafi – Study 1 and Study 2|
|Inrebic (n=96)||Placebo (n=96)||Jakafi (n=155)||Placebo (n=154)||Jakafi (n=146)||Best available therapy (n=73)|
|Number (%) of patients with spleen volume reduction by 35% or more||35 (37)||1 (1)||65 (42)||1 (<1)||41 (29)||0|
|Source: US drug labels.|