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Pfizer PF 06651600- Breakthrough Technology Jak 3
phase 2 release of data expected sept 15, Pfizer will start phase 3 in 2019.
Replies to This Discussion
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Permalink Reply by TC on
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Hi Kim,
Thanks for tracking and posting these updates.
So there's 2 potential treatment tracks;
PF-06651600 = JAK 3 inhibitor
PF-06700841 = a tyrosine kinase (TYK) 2/JAK1 inhibitor
From what I'm reading PF-06700841 (TYK 2/JAK1) had a better improvement in SALT scores, or am I reading it wrong?
If I'm reading it right - 33.6 points for JAK3 and and 49.5 points for TYK2/JAK1 are the improvement in SALT from baseline?
The other interesting thing are the dosages are considerably higher than what we typically see for Xeljanz (10-15mg)
PF-06651600 (200 mg once daily [QD] for 4 weeks, followed by 50 mg QD for 20 weeks)
PF-06700841 (60 mg QD for 4 weeks, followed by 30 mg QD for 20 weeks)
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The results of Tyke / jak 1 are far better than jak 3 and no safety issues are reported. Very strange Pfizer has chosen to go with jak 3. Or there are typo errors in the communicate or at the moment it's quite hard to understand this decision.
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Permalink Reply by kimk on
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Tofacitninub is a jak1,2and3
it would appeal that a new best in class for safety has been born. This is my guess .... The FDA wants safety with AA first, even with Barri for RA (which is very crowded treatment space) they want safety trade off for me too! Now the real question will be safety profile for
1. Concert jak1,2 CTP-543
2. Aclaris jak 3? ATI 501 and 502
i don’t know what ATI is if anyone knows for sure ? I will put on my chart!
The opinions above are my personal views.
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Thanks Kim, I learned something new today.
Mechanism of Action
Tofacitinib is a potent, selective inhibitor of the JAK family of kinases with a high degree of selectivity against other kinases in the human genome. In kinase assays, tofacitinib, inhibits JAK1, JAK2, JAK3, and to a lesser extent TyK2. In cellular settings where JAK kinases signal in pairs, tofacitinib preferentially inhibits signaling by heterodimeric receptors associated with JAK3 and/or JAK1 with functional selectivity over receptors that signal via pairs of JAK2. Inhibition of JAK1 and JAK3 by tofacitinib blocks signaling through the common gamma chain-containing receptors for several cytokines, including IL-2, -4,-7,-9, -15, and -21. These cytokines are integral to lymphocyte activation, proliferation, and function and inhibition of their signaling may thus result in modulation of multiple aspects of the immune response. In addition, inhibition of JAK1 will result in attenuation of signaling by additional pro-inflammatory cytokines, such as IL-6 and Type I interferons. At higher exposures, inhibition of erythropoietin signaling could occur via inhibition of JAK2 signaling.
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ATI 501 (oral) and ATI 502 (topical) are jak 1/3 inhibitors.
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Their press release from 9th July has this
"Aclaris’ investigational topical Janus Kinase (JAK) 1/3 inhibitor (ATI-502)"
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