Jak1 inhibitor GVHD Phase III Clinical Failure.

GVHD is a serious side effect of allogeneic stem cell transplantation and is the most common non-recurrent fatality due to the multiple tissue attacks on the recipient by the donor's immune cells.
acute GVHD symptoms, including the digestive tract, skin and liver, while chronic GVHD is mainly an allergic skin reaction.
this is a relatively rare disease, the specific incidence is unknown, estimated 10-50% of stem cell transplant patients will have GVHD, there is no reliable biomarker to assess the risk.
Itacitinib also has a Phase III clinical phase for chronic GVHD called GRAVITAS-309.
Incyte already has a JAK1/JAK2 double inhibitor ruxolitinib approved through the accelerated approval channel for acute GVHD second-line patients with hormone recurrence, and this product is also in the validation phase III clinical trials of chronic GVHD and acute GVHD.
JAK1 was the first kinase inhibitor to be marketed for non-tumor diseases, and Pfizer's Tofacitinib was approved for rheumatoid arthritis in 2012.
but this compound also has JAK3 activity, may also play a role in efficacy.
interesting is that tofacitinib later found to have a therapeutic effect.
JAK2 itself is also a drug target, and Ruxolitinib is also approved for bone marrow fibrosis because of this activity.
another well-known JAK2 inhibitor fedratinib Sanofi was abandoned and bought cheaply by Impact Biomedicines, which was acquired by New Base for $1.1 billion and successfully listed last year.
the JAK family also has a member called TYK2, and now there are drugs in Phase III clinical, but mainly for psoriasis.
Squibb is a leader in this area, so last year's acquisition of the new base was asked by the FTC to auction the heavy drug Otezla to prevent a monopoly on the psoriasis market.
second-tier GVHD has about 3,000 new patients in the U.S. and 15,000 on the front line, so the front line is clearly a bigger market.
Ruxolitinib is more confident of getting into the first line because he has shown a 55% response rate in the second tier.
but the product has little patent period left and expires in 2028, and Novartis has an interest outside the U.S., so Incyte has the incentive to develop a second-generation drug.
this is a good advantage for the research, and after Bayer and Onyx developed Sorafenib, Bayer has also fought a legal battle over Regorafenib, a derivative of a fluorine-only atom.
Ruxolitinib is the same as the molecular mother nucleus of the two, although it differs from the itacitinib.
Itacitinib has a largeside chain that reduces the binding to JAK2, so the selectivity is better, but this selectivity may also seem to come at a price.
these kinase functions are complex, especially the cogens that may complement each other, and it is difficult to predict where the efficacy will come from.
Incyte started from Ruxolitinib, but because of the anti-inflammatory side, immunoactivated IDO inhibitor Epac's reputation, has worked with a number of large pharmaceutical companies in strategic cooperation, with Mercado has been at the same time began a number of solid tumor first-line phase III clinical.
unfortunately later ECHO301 failed, and now this mechanism is no longer beautiful.
it's a bit disappointing to be out of the division at the start of the new year, but it's a common thing to win and lose.
kinase is still a relatively robust and understanding area, and the overall success rate of many kinase inhibitors in the Incyte product line should now exceed new IO products like IDO.
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