Baricitinib reaching out for the market

It seems that baricitinib gets ready to come to the market. The annual meetings this year have seen a plethora of studies on baricitinib both at the EULAR meeting in London and the ACR meeting in Washington.

Noteworthy: both meetings received different studies or better different aspects of studies. With other compounds abstracts didn’t differ at both congresses. Not so with baricitinib.

Interestingly the crucial study on radiographic progression only appeared at the EULAR meeting. The FDA approved tofacitinib, but EMEA didn’t a couple of years ago. I think this had an impact on baricitinib. If it had an impact on FDA, let’s wait to see if baricitinib is approved or not. Tofacitinb has applied for approval in Europe (March 2016), so Xeljanz should have an advantage of time.

The study by D. van der Heijde and colleagues showed a robust inhibition of radiographic progression for the 4 mg dose of baricitinib.

N.V. Zamora and colleagues came to the following conclusions: 1. baricitinib with or without MTX had better responses as compared to MTX at 12 and 24 weeks (baricitinib+MTX lower withdrawal rate than MTX alone), 2. baricitinib showed similar effects as adalimumab (with higher rates of SAEs). The authors consider baricitinib to be an additional therapeutic option to treat patients with moderate to severe rheumatoid arthritis, who have an inadequate response to other treatment agents.

There will be a study in a few days by Kevin L. Winthrop and colleagues at the ACR Annual Meeting in Washington: “Herpes Zoster in Patients with moderate to Severe Rheumatoid Arthritis Treated with Baricitinib” [Abstract Number: 3027] – which will have to be discussed at the meeting first.

What can we say today? Lilly is committed to bring baricitinib to the market. Let’s see how quickly. I expect approval or non-approval within half a year both for the US and the EU.

Links:

Radiographic progression – EULAR [THU0168] D. van der Heijde , M. Dougados , Y.-C. Chen, M. Greenwald , E. Drescher , R. Klar , L. Xie , I. de la Torre , T.P. Rooney , S. Witt , D. Schlichting , S. DeBono, P. Emery: Baricitinib Inhibits Radiographic Progression of Structural Joint Damage at 1 Year in Patients with Rheumatoid Arthritis (Ra) and an Inadequate Response to csDMARDS. DOI: 10.1136/annrheumdis-2016-eular.1611

Meta-Analysis - EULAR [SAT0177] N.V. Zamora , J. Tayar , M.A. Lopez-Olivo , R. Christensen , M.E. Suarez-Almazor: Baricitinib for  Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. DOI: 10.1136/annrheumdis-2016-eular.4449

Protein Kinase Inhibitors / Small Molecules in Rheumatology – an Update 2016

I have already written about hype or hope in protein kinase inhibitors. Tofacitinib seems to have the data needed, to get approval by EMEA in Europe, at least Pfizer applied for approval. So, in August 2016 I feel it’s time to ask again: where do we stand and how much hype is left?

The protein kinase inhibitors were introduced with high hopes and expectations, but the hype fell off, when EMEA asked for more data on tofacitinib. Now, about three years later, Pfizer has applied for approval of tofacitinib in Europe. And I see more activity on small molecules recently.

Due to introducing small molecules, we have learned much on what is driving inflammation in rheumatic diseases during the last decade.

Here is a chart, in which I put my updated knowledge:

Green – approved

Yellow – still in the race

Red – out of the race
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Apremilast is approved in the US and the EU. Tofacitinib is appoved at least in the US and applied for approval in the EU. Baricitinib applied for approval in the US. Abt-494 is investigated in a phase 3 study (SELECT-COMPARE); OT: please name the child. Peficitinib (ASP015k) is investigated in Japan. EULAR 2016 has seen pahse 2b studies by decernotinib and filgotinib. I might have overrated HM-0523, as I am skeptical about about the value of Syk inhibitors in the therapy of rheumatoid arthritis and I haven't seen any new study after the ACR 2014 Meeting. All in all, more action to get small molecules to the market.

I guess that the pharmaceutical industry isn’t prudent enough not to overprice small molecules, so that our patient's needs are addressed. Prices should be oriented in the range of methotrexate and leflunomide.

Links:

http://rheumatologe.blogspot.de/2015/11/protein-kinase-inhibitors-after-acr.html http://rheumatologe.blogspot.de/2013/06/protein-kinase-inhibitors-hype-or-hope.html

http://rheumatologe.blogspot.de/2014/01/protein-kinase-inhibitors-where-do-we.html

http://rheumatologe.blogspot.de/2014/06/protein-kinase-inhibitors-at-eular-2014.html

http://rheumatologe.blogspot.de/2015/11/fostamatinib-at-acr-2015-meeting-in-san.html

https://en.wikipedia.org/wiki/Federal_Joint_Committee_(Germany) http://rheumatologe.blogspot.de/2015/11/filgotinib-at-acr-2015-meeting-in-san.html

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Protein Kinase Inhibitors after the ACR 2015 Meeting in San Francisco – how much Hype is left?

I have already written about hype or hope in protein kinase inhibitors. Now, after the ACR 2015 Annual Meeting in San Francisco it’s time to ask: how much hype is left?

Here a chart, I’ve prepared only a year ago:

Xeljanz (tofacitinib) is on the market in the US for the treatment of rheumatoid arthritis, but still lacks approval in Europe.

Otezla (apremilast) has been approved in the US and later in Europe for the treatment of psoriatic arthritis.

One study on fostamatinib came up, but only on bovine cartilage cells – but still unexpected for me; see: links.

Baricitinib had been discussed in several studies, posters, talks at the meeting; I’ll write on the studies in detail, soon.

Addendum: somehow I've left out filgotinib. Filgotinib is still in the race. Please look for more details under links.

This list above is incomplete, I know, but it shows how many hopes we had. I think that too many pharmaceutical companies tried to run for a small molecule, which is easier to produce, but might be sold at a high price. This mass of different molecules with facets of different effects was fuelling the hype, which peaked, when Xeljanz got the FDA approval. But I assure you: the hype is gone. Xeljanz is struggling for EMEA approval. Fostamatinib like most others have been abandoned as potential drugs. Otezla is approved in Germany, but will hardly be used because of failure of obtain a positive GBA ruling. The GBA (Federal Joint Committee) “exerts a direct influence on the healthcare provisions”; for further details look at Wikipedia, you can use the link below. And I think that Baricitinib will reach approval, too.

I hope that the pharmaceutical industry is prudent enough not to overprice small molecules, so that our patient's needs are addressed.

Links:

http://rheumatologe.blogspot.de/2013/06/protein-kinase-inhibitors-hype-or-hope.html

http://rheumatologe.blogspot.de/2014/01/protein-kinase-inhibitors-where-do-we.html

http://rheumatologe.blogspot.de/2014/06/protein-kinase-inhibitors-at-eular-2014.html

http://rheumatologe.blogspot.de/2015/11/fostamatinib-at-acr-2015-meeting-in-san.html

https://en.wikipedia.org/wiki/Federal_Joint_Committee_(Germany)
http://rheumatologe.blogspot.de/2015/11/filgotinib-at-acr-2015-meeting-in-san.html

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