Pfizer’s JAK inhibitor Tofacitinib EMA Application Validated
Pfizer JAK-3 press release
“Pfizer Announces European Medicines Agency Acceptance Of Regulatory Submission For Tofacitinib For The Treatment Of Rheumatoid Arthritis: Pfizer Inc. (NYSE:PFE) announced today that its Market Authorisation Application for tofacitinib (development code CP-690,550), a novel, oral JAK inhibitor being studied for the treatment of moderate-to-severe active rheumatoid arthritis (RA), has been validated by the European Medicines Agency (EMA). Validation means that the EMA has confirmed that the application is complete and the agency is beginning its review procedure.”
Pfizer at the 2011 American College of Rheumatology Meeting
Between JAK, Enbrel, and Celebrex, Pfizer visibly dominated the entrance to the Exhibit Hall at ACR 2011. In the photos, you can see the edge of the large purple and blue rings seeming to suspend from the sky. We told everyone to look for us under the Pfizer “halos.” In an article for Pharmaphorum, I described Pfizer’s imposing presence at the 2011 ACR meeting:
“Pfizer dominated chatter about the treatment pipeline, presenting data about its novel JAK inhibitor for an oral treatment of Rheumatoid Arthritis. The buzz was enough to force some of their oral sessions to broadcast a feed into overflow spaces. Selected Pfizer investigators and representatives reported on the numerous phase 2 and 3 ORAL Trials as well as long-term extension studies.
“The JAK compound, tofacitinib, has now been tested in almost 5,000 RA patients in approximately 35 countries as mono-therapy and in combination with other disease modifying medications. Efficacy was similar to IV and injectable Biologics that are currently approved for RA treatment with approximately 65% of patients achieving at least ACR20 (20% reduction in disease activity). Patient reported outcomes also showed significant improvement and radiographic progression was arrested when measured at six months with the higher dose.”
High expectations for Janus kinase (JAK) inhibitors
According to Nature Reviews Drug Discovery, after several years of research, we are still learning to understand how “small molecule” JAK inhibitors modify immune activity and how to use them to create therapies. We’ll be watching for Pfizer to also file with the US FDA, possibly in the next year. Other JAK inhibitors are close behind Pfizer’s tofacitinib including Eli Lilly’s (Incyte) INCB28050 (JAK 1 and 2 inhibitor). Phase II studies are also underway by for JAK-1 by Galapagos and for a JAK-3 by Vertex. Here’s a list of JAK inhibitors in the pipeline.
More about the JAK-3 aka tofacitinib (Pfizer ORAL trials)
- Tofacitinib / CP-690550 aka Tasocitinib Succeeds in Pfizer’s 2nd Phase 3 Trial
- Rheumatoid Arthritis Drug Trials for Tasocitinib aka CP-690550
- New Way to Report Response in RA Clinical Trials?
I think an oral med is especially exciting, because the cost may be lower than the injectibles. I don’t really know, but pills in generally seem to be somewhat cheaper than injectable anything. The cost of the injectable biologics seems a sticking point for many patients… I met with some new friends with RA last week, and I was shocked at how many docs do not start new RA patients on the biologics right away, instead starting with cheaper meds.
Treatment paradigms are still all over the map, aren’t they. Some say the “pyramid” for RA treatment is dead. But I say, it seems more “re-named” as the “step-up approach.” Not much different from the patient viewpoint. Cheaper meds are fine if the patient gets remission from them – but since remission is rare… aggressive treatment is usually best.
I think cost depends more on the decade-plus of research prior to the production of the pills – if it takes billions to get this drug to market, some say it’s that first pill thats worth, say 2 billion – of course no one can pay that, so a company has to choose a price that will make a profit for them but still be saleable…
I think some of the cost must be related to how the home injectables (all of them?) need refrigeration, overnight shipping, etc. It wouldn’t cut the cost much, to have a shelf-stable pill, but it might.
I agree with the treatment paradigms…I was dx in 1982 when you started with aspirin, and things like gold and mtx were last resorts. A few years ago, dr’s seemed to be starting on DMARD’s right away. Recently, I’m running into people who are started on plaquenil as a first med for RA. What’s up with THAT?
Funny you say that Ms.M was diagnosed in late April this year…took 4 calls to find a rheumy that had openings then the wait list was 4 mths. finally called another rheumy and they had a check list in order to get me in… he saw me within 1 week and started me on Sulfasazine, planiquil and predisone and folic acid. they said we start with the cheapest method first then we will take it from there….they just upped my sulfasalazing to 6 pills a day and lowered the pred to 5mg….they also tell me I have the anti ccp that means I am harder to treat?
Stephanie,
There is a national shortage of rheumatologists…even as an established patient, at certain times of the year I have to wait to get into my rheumy.
Sorry about your recent dx! The good news is, there are tons of meds now (more options for treatment), and more coming down the pipeline all the time. (((hugs)))!
I think doctors have to start with the cheapest and least toxic drugs to see if it will control your symtoms before moving on to the more expensive injectables and infusions…Why would anyone want to take those first if they could get by with something cheaper and perhaps less toxic? Also if you start at the top you have no where to move forward…These rheumatic diseases last a lifetime and we have to pace ourselves or risk running out of options way too soon…Some people are lucky enough to stay on one medication for 5 or 10 years but many of us have to keep changing every 6 months or so before finding one that works longer or at all…I agree with how most doctors approach this…It is not a race to the finish line…We must remember to pace ourselves or run out of medications to try…
Jewell
These JAK inhibitors are great news, I’ve seen research that they show response in those of us that don’t respond to the TNFa inhibitors. Seems like the JAKs are further upstream in the RA process.
Good stuff Kelly, thank you 🙂
I agree with Jewell. Why not try the least toxic med first, even for a bit to see. I know early intervention is key. My daughter had an anti-CCP above 250 (not sure how high above or if I want to know, but it just said greater than 250) and a rheumatoid factor of 141 last spring. We took her to Mayo and one of their top rheumatologists whom she saw only started her with Plaquenil and a small dose of prednisone and never mentioned it being harder to treat or more aggressive with the high anti-CCP, which I have read though. A month later she saw a rheumatologist in Minneapolis as that is where she settled after graduating from college last summer and he too thought Plaquenil was fine to be on along with the low-dose prednisone as she was doing basically quite well, exercising, dancing, spending the summer in NYC. She does have occasional joint pain but thankfully none of the severe pain I read about. Just this month now he said we need to try some methotrexate as he is still seeing inflammation in some of the joints and I asked about going to biologics right now instead and he said: 1) Your insurance company likely will not pay before trying methotrexate first. 2) I don’t think she is ready for them. He is a professor at the U of M also so I suspect he knows his stuff. Hope so anyway.:) A lady I know had a rheumatoid factor of over 800 and was just started on Plaquenil as well and actually did quite well on that alone for a year before having to add methotrexate, which kicked her into remission and now is on no meds 12 years later. Very lucky!
I think the answer to the tiered drug approach is based on several things. 1)safety: plaquenil is safer than MTX, MTX is safer than the biologics 2)cost: again, the same sequence and finally 3)insurance: your insurance will always require that you try the cheaper drugs first before paying for the more expensive. If we ever got to a place where someone developed a drug that would induce remission in almost everyone, I can guarantee that your insurance wouldn’t pay for it if it were expensive and there were cheaper drugs that might work!
This is the trial drug I’ve been on for over a year. I never did respond positively to anti-TNFs. Never had a substantial response to any drug treatment until now. I saw an article on the local news one night. Called the treatment center the next day and got in by the end of the week. I consider this a God-send. Only drawback is having to take MTX with it. I hate methotrexate-hate-will check to see if I can continue with JAK but stop the metho.
In addition to helping very much with my arthritis, I also have MS which some have said was caused by one of the anti-TNFs. Every other treatment has still produced demyelinating lesions-but not this one!!!! No new lesions since I’ve been on it. Can hardly wait until it is available for everyone!!!!!