With my now intense interest in the FDA approval process for untreatable conditions I was curious on that for Rux. It had an extraordinary fast approval. Its phase 1 trial started in 2007, just two years after the discovery of the Jak2 mutation. Best I can tell its R&D started 2006 and it was approved for use late 2011. This is less than half a typical successful drug takes to get there, and resulted at least partly from its accelerated FDA status and success against a largely untreatble condition.
If the two new v617F targeted agents (AJ1-11095 , INCB160058 see link below) were to succeed and follow this schedule MF pts would be taking it in 2028. If the current ph1 trials go well maybe that could happen. But we know it's all about unknowns.
Some more findings on Rux: Its targeting of Jak1 along with Jak2 was apparently intentional with MF features in mind. So Jak1 is not “off target”. This is notable in light of the pre-clinical VGT-1849A discussed recently (see below). Their indication is PV and they specifically took out the Jak1 target. Maybe PV has only side effects and no benefit by targeting Jak1.
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See below for the historical refs:
Rux trials:
Phase 1-2 MF
clinicaltrials.gov/study/NC...
Start June 2007, primary completion Dec 2007.
Phase 3 MF
clinicaltrials.gov/study/NC...
Start Aug 2009, primary completion Nov 2010.
Approval
November 16, 2011
It’s about 4 years from 1st trial start to patients using it.
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They had control of their targets. Re Jak1, 3:
ashpublications.org/blood/a...
“INCB018424 (Rux) was designed to spare JAK3…”
“JAK1 and JAK2 may interact, resulting in their transactivation.” so “we hypothesize that selective inhibition of both kinases (Jak1 and 2) may provide greater clinical benefit”
“Most patients with primary myelofibrosis …(are) consistent with our observation of JAK1 hyperactivation. Accordingly, we evaluated the effectiveness of selective JAK1/2 inhibition”
I have posted on this combo target maybe enabling the VAF reductions in PV. Trials of VGT-1849A, below, should answer this.
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(Nov 2011) Incyte ($INCY) has won an accelerated FDA approval for ruxolitinib (originally dubbed INCB018424 ), its JAK1 and Jak2 inhibitor…
fiercebiotech.com/biotech/i...
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A recent thread discussed VGT-1849A that is intended to leave Jak1 alone:
healthunlocked.com/mpnvoice...
(VGT-1849A) seeks to reduce the risk of infection and toxic effects that are seen with inhibitors also blocking JAK1, JAK3, TYK2.
This may be that PV pts don’t have the JAK1 hyperactivation seen with MF and which apparently motivated Rux to also target Jak1.
Best treatment for Post PV/MF ?
New MF drugs in development by Incye
