Tofacitinib / CP-690550 aka Tasocitinib Succeeds in Pfizer’s 2nd Phase 3 Trial
A new name and new milestone for tofacitinib
Pfizer announced Friday that CP-690550 tofacitinib (formerly tasocitinib) met its goals in its second phase three clinical trial for moderate to severe Rheumatoid Arthritis. Tofacitinib is a JAK 3 inhibitor, an oral treatment for RA with a different approach than current Biologic RA treatments.
According to Pfizer, over 4,000 patients in 35 countries have been treated with tofacitinib so far. They report that Phase 3 clinical trials demonstrated better improvement than placebo of symptoms of RA as measured by ACR 20 after six months and DAS28(ESR) less than 2.6 and improved clinical function (by HAQ DI). Details were not released.
Does this drug sound familiar? We first reported on tofacitinib one year ago when it was being called tasocitinib: Rheumatoid Arthritis Drug Trials for Tasocitinib aka CP-690550.
Last fall, Pfizer reported that their first phase 3 clinical trial demonstrated that 59.8% of patients reached ACR 20 (a 20% improvement of symptoms) at 5 mg doses and 65.7% of patients reached ACR 20 with 10 mg doses, taken twice daily. The percentages of patients reaching ACR50 were 31.1% and36.8%. For ACR70, the rates were 15.4% and 20.3%. It looks like thirty-four percent of patients at the higher dose did not reach 20 percent improvement.
Why tofacitinib is a new approach to Rheumatoid Arthritis treatment
Tofacitinib (CP-690550) is considered a new approach to treating Rheumatoid Arthritis because it seeks to inhibit Janus kinase (JAK), a protein which acts as a hub in the cytokine network that creates inflammation. Current treatments for RA interfere with the receptors of various immune cells such as T-cells (Enbrel) or B-cells (Rituxan) or IL-6 (Actemra). Tofacitinib targets a broader phase of the inflammatory process.
A USB video we received at ACR in November clearly explains the fundamental role that JAK plays in the intracellular signaling pathway.
“The dysregulation of multiple cytokine signaling pathways plays a critical role in the pathophysiology of Rheumatoid Arthritis. A continuous progression of uncontrolled cytokine-mediated inflammatory cascades results in chronic activation of multiple cell types including T-cells, B-cells, monocytes, macrophages and osteoclasts. These dysregulated signaling pathways contribute to the persistent inflammation, systemic illness, and joint destruction that is characteristic of RA… In fact, these cytokines utilize JAK signaling pathways to regulate the inflammatory activity of many cell types involved in RA including T-cells, B-cells, and osteoclasts. Additional studies showed that JAK levels are significantly elevated in the RA synovium.”
Tofacitinib is not the only new oral RA med in the pipeline
I found this list of oral kinase RA treatments currently in clinical trials, producing new hope for not only RA patients but also for patients with other autoimmune inflammatory diseases such as psoriasis and Crohn’s. Two that are close behind Pfizer’s tofacitinib are Eli Lilly’s (Incyte) INCB-28050, a JAK 1 & 2 inhibitor, and AstraZeneca’s fostamatinib (R788), the first oral SYK inhibitor.
Read Pfizer’s tofacitinib press release on Fierce Biotech.
Visit the Oral Trials site set up by Pfizer for tofacitinib.
Recommended reading:
- American College of Rheumatology Annual Meeting 2010
- Which Biologic Treatment Should RA Patients Try Next?
- 20 Facts about Biologic Medications for Rheumatoid Arthritis
- More posts on Biologics for Rheumatoid Arthritis
That does sound interesting. I like the idea of an oral medication over an injection. I told my husband that if it comes down to me having to get injections, I think I’d rather suffer, because I don’t think I can give myself an injection. Besides, I’m becoming a pro at taking oral medications… Every Friday night, I take 9-12 pills, depending on my pain level.
I like the idea of something that works – since I haven’t found that yet, each new treatment gives me hope that it may yet come! Kat – I have faith that if you ever do come to the point of needing injections, you’ll find a way to handle it if it means you can take care of your family and be around longer. One day at a time.
I think it’s great that you can tolerate oral medication. Unfourtunantly I couldn’t so I did have to go to injection and the thought terrified me, I you do have to change over just know that it gets better over time and I was scared out of my mind at first too.
-maddie
Hopefully this will be good enough for approval. Did they present any safety data at the ACR last year? Did they give any projections on the submission date? I just hope the FDA doesn’t drag their feet on this one too. They’ve been pretty slow to act lately. Sigh.
I think it’s good that they are developing new meds that work differently – better options if the others don’t work.This is, of course, good. But, better than a placebo? Gosh, I hate that phrase. Maybe I’m not looking in the right place, but I haven’t yet seen much research that compares these drugs head to head – which one might work better than which others for which patients. There must be some way of telling – or there should be some research going on to figure that out – or am I just practicing wishful thinking? Right now they just try them until they get one that works – how to choose? It’s so frustrating. And for those who fail drug after drug, time wasted, pain and damage.
Patient tailoring and individualized medicine has a big push in the medical industry. Every company I know of is pursuing this. You have to start somewhere with a trial. Eventually you’ll see studies with combinations of different agents. Patient tailoring is already used quite often for other diseases like cancer.
Here’s a link to a talk by Dr Edward Keystone, a noted expert. It is very clear and optimistic. A little pro-Canada but that’s not the issue
http://www.arthritis.ca/local%20programs/ca/publications%20and%20resources/presentations/default.asp?s=1
Just click on the one that says “The Most Exciting Time In The History of Arthritis”
Annette
I just looked at that video today, and made my family watch all 96 minutes of it. Very informative about various RA aspects. Couple of things that some may disagree with (swelling present to make diagnosis), but yes, in general it was optimistic. I especially liked the part about the connection to peridontal disease. Last month, while roving the net about bacteria and RA links, I came across some research on RA folks having 2 higher levels of bacteria that originate in the mouth, tooth pulp to be specific. It was like a slap in the face for me because of this:
I had a botched deep cavity filling that hurt for 6 weeks after, and finally got it filled by a competent dentist after refusing to believe I needed a root canal by the first one. One month after the tooth was fixed, I had a painfully swollen finger, that the doctor said I just jammed, a month later I started having jaw pain on one side that I had my bite realigned for,thinking that would correct it. Then another month later the other symmetrical finger swelled like crazy, again, a new doctor did an RF test, negative, gout test negative… and left it at that. Was still having jaw pain on one side, that abruptly stopped in July after 6 months. Not much for the next few months untill I had a full blown onset of RA on x-mas eve night in the shoulder and it’s been non-stop since. I never saw a doctor in 8-10 years prior to this, for anything. I cant help but link the bad job on the cavity filling as a pre-cursor to all this. Who knows.. but it certainly gave me some food for thought. Especially when the good dentist said that the botched dentist “really stirred up the pulp of your tooth and didnt get all the decay out before filling”
grrrrr.
I have been in this CP-690-550 clinical trial since August of 2011, having been lucky enough to be on the actual med and not a placebo, I was bedridden and wheelchair ridden until 1 week after taking my first dose. The results have been magnificent, and my quality of life has greatly improved. I am living life without pain, dancing, enjoying my Grandchildren and feel like a teenager (I am 63 yrs old) No side effects to speak of and the RA medicine of the future. God bless Pfizer and their research department. I hope this medicine gets the approval it greatly deserves.
Thanks for taking time to comment, Rose. I’m so glad to hear of your wonderful response.
Maybe it will work for others of us who have not ever had any relief! Still at that almost bedridden stage every day.
Katie, I hope your RA never reaches the point where you have to use injectable medications, but trust me, if giving yourself a shot makes the difference between being able to brush your teeth, dress yourself, walk, etc., or not, you will do whatever you have to do to lessen the pain and to have at least a little bit to a lot of your old life back. Sometimes the shots do hurt, but that pain quickly goes away. RA is a horrible disease. Maybe someday doctors will be able to tell which cells are causing trouble and target meds that work better than trying this one, and then that one, etc. trying to find what works best for each individual. I found out that RA patients have a higher risk of osteoporsis, so everyone out there, please talk to your doctor about calcium supplements if you are not already taking them. Bones that break on their own aren’t much fun. Again, thank you Kelly for some encouraging news.
I have been in the clinical trial for Tofacitinib (CP690500) for 18 months. I have my life back again. I am now 65 yrs old and first started feeling the syptoms of RA in 1996. This drug is incredible! I began to feel better after only 3 days and progressed from there. I am now able to do much of what I had given up on because of debilitating pain. I too, have not had side effects. I hope this drug is approved soon and the price reasonable so many more with RA can get their lives back.
MJ – I am happy that you’ve seen such a remarkable progress with Tofacitinib, and without side effects to boot! I’m looking forward to the day when it’s approved and priced reasonably – I’m really concerned that it will be priced through the roof & that the millions of people who are suffering won’t be able to afford it. The government really need to put a cap on drug company pricing!
The hidden surprise in this drug is that since it is a JAK inhibitor, it can be used to treat two disorders caused by HTLV: HAM and ATL. HAM results in being in a wheel chair, and ATL results in death from a rapid leukemia. 25 million HTLV sufferers are going to want this drug so they can continue to walk and literally stay alive.