Again
there is a hype on small molecules as JAK-inhibitors are on the market and the
drug are sold at exorbitant prices – for a small, less complex molecules as
compared to large, complex molecules like MABs with much higher production
costs. So it is understandable that companies try to come to the market with
such drugs. Filgotinib is presented in 10 studies at the 2019 EULAR Meeting in
Madrid; as tofacitinib and as baricitinib.
Bruton’s
tyrosine kinase (BTK) plays an essential role in B cell development and is
thought to be involved in the pathogenesis of RA. There are 5 studies on
different BTK-inhibitors at the 2019 EULAR Meeting.
I’ve had
a discussion on twitter with friend and colleague Dr Irwin Lim
(@_connectedcare) on Twitter yesterday [1]. So I looked deeper into
BTK-inhibitors.
Acalabrutinib
(Calquence®)
Acalabrutinib
(Calquence®) by AstraZeneca: study completed, but no published data on outcome
(DAS28) in April 2015. Nothing at the 2019 EULAR Meeting. Calquence® has been
approved by the FDA and the EMA for the treatment of mantle cell lymphoma
(MCL).
AC0058
AC0058
by ACEA has an ungoing study on systemic lupus erythematodes (NCT03878303),
which is still recruiting. I haven't found a study on rheumatoid arthritis.
BMS-986142
BMS-986142
by Bristol-Myers Squibb: study completed, but no published data on outcome
(ACR20, ACR70) in Feb. 2016. Nothing at the 2019 EULAR Meeting.
Evobrutinib
Evobrutinib
by Merck: study ongoing (ACR20) in Jul. 2017. Nothing at the 2019 EULAR
Meeting.
Fenebrutinib
Fenebrutinib
by Roche/Genentech: study completed (ACR50) in Sep. 2016. There are two
studies. St. Cohen and colleagues concluded in phase 2 study: “FEN
[Fenebrutinib] demonstrated higher efficacy rates than PBO [placebo] for ACR50
at W12 in both MTX-IR and TNF-IR [inadequate response] populations, and was
similar to ADA [adalimumab] in MTX-IR pts. The overall safety profile of FEN
was acceptable.“ [2] The other study is a cell study (THE BTK INHIBITOR,
FENEBRUTINIB, EFFECTIVELY MODULATES B AND MYELOID CELL BIOLOGY IN RHEUMATOID
ARTHRITIS PATIENTS).
Poseltinib
Poseltinib
(LY3337641) by Eli Lilly: study terminated because of lack of efficacy (ACR20)
in Aug. 2016. Early in 2018 Eli Lilly has halted a phase 2 trial on rheumatoid
arthritis after looking at the mid-study data. Probably the efficacy goal
wasn’t likely to be met (ACR20). [3] These study results will be discussed at
the 2019 EULAR Meeting on Saturday.
Spebrutinib
Spebrutinib
by Celgene failed to meet primary outcome (ACR20) in Oct. 2013. Nothing at the
2019 EULAR Meeting.
TAS
5315
TAS 5315
is a BTK inhibitor by Taiho. There are two animal studies at the 2019 EULAR
Meeting.
Tirabrutinib
Tirabrutinib
(ONO-4059) by Ono Pharmaceutical/Gilead Sciences: there had been some efficacy
in a CIA study, but nothing more than a phase 1 study for rheumatoid arthritis
so far.
Irwin,
you’ve written: Fenebrutinib in RA - some promise #eular2019, and I have to
admit, I come to the same conclusion. I had answered: BTK inhibitor? There have
been posters for a long time. Is the small molecule hype back? #EULAR2019
#Fenebrutinib. There is some promise as fenebrutinib showed a similar response
like adalimumab. Now, we’ll have to wait for a phase 3 study and of course the
approval by FDA, EMA and other countries’ boards. Hopefully, the price level
will be lower than it is now with other small molecules.
Links:
[1]
Orininal Tweet by Dr Lim:
https://twitter.com/_connectedcare/status/1138821551229493250
[2] St.
Cohen and colleagues: Ann Rheum Dis, volume 78, supplement 2, year 2019, page
A80
http://scientific.sparx-ip.net/archiveeular/?view=1&c=a&searchfor=Bruton%E2%80%99s%20tyrosine%20kinase%20&item=2019OP0025
[3]
https://www.fiercebiotech.com/biotech/lilly-scraps-rheumatoid-arthritis-trial-after-interim-review
.
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