I’ve selected a few MABs, which are possible candidates for the treatment
of rheumatoid arthritis with a few additions, which could be more useful in
psoriatic arthritis. Even if research has been stopped for some, it might not
be that the case is closed permanently. Pharmaceutical firm look at the MABs
from an investor’s point of view that means research will be directed at the
most promising MAB first.
Afasevikumab
Afasevikumab is a human monoclonal IgG1κ antibody targeting IL-17A and
IL-17F. There had been a phase 1 trial in “autoimmune disorder”, but this
research has been stopped. Nothing on PubMed.
Links:
Bimekizumab
(UCB4940)
Bimekizumab (UCB4940) is a monoclonal antibody targeting IL-17A and
IL-17F. S. Glatt and colleagues presented a study at the EULAR 2016 meeting in
London. In this proof-of-concept-study bimekizumab demonstrated rapid onset and
sustained efficacy on disease activity both in skin and joints. AdisInsight
reports phase II studies in ankylosing spondylitis, psoriatic arthritis, plaque
psoriasis, and rheumatoid arthritis as well as ulcerative colitis.
Links:
Briakinumab
Briakinumab (ABT-874) is a human monoclonal antibody that targets IL-12
and IL-23. Last entry on the drug on this blog had been after the 2012 ACR
Annual Meeting, where nothing new had emerged. Further drug development for
psoriasis had been stopped in 2011. There is one phase 2b study however
on the possible use of briakinumab in Crohn’s disease.
Links:
Brodalumab
Brodalumab is a human monoclonal antibody targeting the IL-17 receptor
and inhibits the binding of several types of IL-17 to the receptor. The
Dermatologic and Ophthalmic Drugs Advisory Committee to the FDA has voted for
the approval of brodalumab for adult patients with moderate-to-severe plaque
psoriasis (July 2016) despite safety concerns (suicides). I have already
mentioned the problem in a blogpost on Apremilast. Nothing on arthritis studies
at both the 2016 EULAR and ACR Annual Meetings.
Links:
Clazakizumab
(ALD518)
Clazakizumab (formerly ALD518) is a humanized monoclonal antibody
against IL-6. I had written about Clazakizumab after the EULAR 2014 Annual
Meeting in Paris. I haven’t seen any new study at both the 2016 EULAR and ACR
Annual Meetings.
There had been a study in 2015 by M.E. Weinblatt and colleagues that
showed treatment with clazakizumab in combination with methotrexate or
clazakizumab monotherapy in patients with rheumatoid arthritis was well
tolerated, and patients achieved significant improvements in disease activity
with higher rates of remission.
P.J. Mease and colleagues published a study on clazakizumab in patients
with psoriatic arthritis. They concluded: “This is the first clinical trial of
an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment
option for musculoskeletal aspects of PsA, but because of the lack of a dose
response in this study, further studies are required to confirm the appropriate
dose.” The study doesn’t make me as enthusiastic as the authors. Maybe
TNF-alpha is a much better target in psoriatc arthritis that IL-6.
In May 2016 “Alder BioPharmaceuticals has licensed exclusive worldwide
rights to its Phase II inflammation candidate clazakizumab”.
Summing it up, clazakizumab might be a candidate, but approval as a
drug is still a far goal.
Links:
Clenoliximab
Clenoliximab is a monoclonal antibody against CD4, which has been
investigated for the treatment of rheumatoid arthritis. There had been a study
by T.W. Hepburn in 2003 with the conclusion: “Decrease in the density of CD4 on
the T-lymphocyte surface is caused by antibody-mediated stripping.” As no other
study has been published afterwards, we may well assume, that clenoliximab is
history in the treatment of rheumatoid arthritis.
Links:
Fezakinumab
Fezakinumab is a human monoclonal antibody targeting IL-22.
Adinsight reports discontinuation of studies in psoriasis in 2011. I haven’t seen any new study at both the 2016 EULAR and ACR Annual
Meetings. So I guess, we won’t see more of fezakinumab in rheumatology.
Links:
Fletikumab
Fletikumab is a monoclonal antibody targetting IL-20 for the treatment
of rheumatoid arthritis. Careful, it’s IL-20 and not CD20. As IL-20 plays a role in keratinocytes during inflammation, one should
think more of a possible usefulness in treating psoriatic arthritis, or even
more in placque psoriasis, than rheumatoid arthritis. Nevertheless there had
been phase 2 studies in rheumatoid arthritis patients, which had been
discontinued in September 2014. There haven’t been any new studies at both the
2016 EULAR and ACR Annual Meetings. Dead end?
Links:
Ixekizumab
Ixekizumab is a humanized monoclonal antibody, which targets IL-17A and
is also known as LY2439821. I’ve written already about ixekizumab several
times, especially after 2013 EULAR Annual Meeting in Paris. P.J. Mease and
colleagues presented a study at the 2016 EULAR Annual Meeting (SPIRIT-P1). They
looked at 304 patients with psoriatic arthritis. The authors concluded: “IXE
[Ixekizumab] demonstrated clinically significant improvement in signs and
symptoms of PsA including arthritis, dactylitis and enthesitis as well as skin
manifestations across treatment groups in the EP [Extension Period].” More
studies were presented, like effect on work productivity, quality of life and
so on. There have been even more studies at the 2016 ACR Annual Meeting. FDA
and EMA approved Taltz (ixekizumab) to treat adults with moderate-to-severe
plaque psoriasis. This and the commitment to studies on psoriatic arthritis
will most probably lead to the approval of Taltz for rheumatologic indications
in the future.
Links:
DOI: 10.1136/annrheumdis-2016-eular.1172
Lulizumab
pegol (BMS-931699)
Lulizumab pegol is a monoclonal antibody, which targets
CD28. Maybe you remember another MAB targeting CD28 -: TGN1412, which caused
multiple organ failure. “CD28 has also been found to stimulate eosinophil
granulocytes where its ligation with anti-CD28 leads to the release of IL-2, IL-4,
IL-13 and IFN-γ.” But it seems that lulizumab is past this point of concern. At the
moment phase 2 studies in patients with Sjogren’s syndrome are under way. A
study in systemic lupus erythematodes is still recruiting patients. There
haven’t been any studies presented at both the 2016 EULAR and ACR Annual Meetings.
Links:
Mavrilimumab
Mavrilimumab
is a human monoclonal antibody for treatment of rheumatoid arthritis, which
targets human granulocyte macrophage colony-stimulating factor receptor
(GM-CSF-R). I’ve followed the development of mavrilimumab closely since 2012
(please look at my blog).
G.R. Burmester and colleagues
presented a study at the 2016 ACR Annual Meeting [Abstract 1616]:
“Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor
Receptor-α Monoclonal Antibody: Long-Term Safety and Efficacy for up to 158 Weeks
of Treatment in Patients with Rheumatoid Arthritis”. Data comes from an open
label extention study. The authors conclude: “[…] Mavrilimumab
100 mg eow is suboptimal compared with 150 mg eow in DMARD-IR pts; however,
efficacy results remain comparable with previous studies, validating the use of
mavrilimumab to target GM–CSFR-α.” So I guess it doesn’t come as a great surprise that there still isn’t
any move towards approval by FDA or EMA. And let me add – where is data on
radiographic progression?
Links:
Ocrelizumab
Ocrelizumab is a humanized anti-CD20 monoclonal antibody that targets
mature B lymphocytes. But ocrelizumab
has been abandoned in rheumatology (RA and SLE) in 2010 because of excess
deaths due to opportunistic infections.
But now FDA granted a breakthrough status for ocrelizumab in multiple
sclerosis. The FDA would be well advised not to accelerate the process for
approval. In rheumatology only 200 mg were supposed to be safe. And now
they test 2000 mg. The FDA will come to a decision by the end of 2016.
Links:
Ofatumumab
Ofatumumab is a human monoclonal antibody which targets the CD20. I had
written about ofatumumab just before the 2013 EULAR Annual Meeting.
I had hoped that the EULAR 2013 meeting would bring more information
than a phase 1/2 study, but it didn’t. There haven’t been any new studies at both the 2016 EULAR and ACR Annual
Meetings. Ofatuzumab is available as Arzerra (sounds like a Basque word to me)
in the indication chronic lymphatic leukemia.
Links:
Olokizumab
Olokizumab is a humanized monoclonal antibody that targets IL-6. I had written
on olokizumab earlier this year. MC
Genovese and colleagues published at both the 2016 EULAR and ACR annual
meetings. No earth-shattering break through data, though.
Links:
Pateclizumab
Pateclizumab is a humanized monoclonal antibody that binds to lymphotoxin
alpha, which is also known as Tumor necrosis factor-beta (TNF-β). I’ve written about pateclizumab right after the
2013 EULAR Annual Meeting: “I don't think that pateclizumab will make it to the
market as the demand for modest improvement isn't too big with better
alternative options already in use. I'm a bit disappointed as two years ago
[2011] I thought targeting lymphotoxin-αlpha
could be an interesting approach. I guess we'll have to wait if pateclizumab is
abandoned silently.” There
haven’t been any studies presented at both the 2016 EULAR and ACR Annual
Meetings. I’ve
lately written on Google+: “The story of pateclizumab ends here. A dead end.“
Links:
Perakizumab
Perakizumab is a humanized monoclonal antibody targets IL-17A.
Adisinsight tells us, that a phase 1 study for psoriatic arthritis has been
discontinued in July 2012. A search in Pubmed didn’t yield any study paper on
perakizumab. My guess -: it’s a dead end.
Links:
Placulumab (CEP-37247)
Placulumab is a human monoclonal antibody that targets TNF alpha. Further
development of placulumab has been discontinued in 2012. There had been an
abstryact at the 2013 ACR Annual Meeting by Matthew M. Seavey and colleagues [#
2316]: “Anti-Human TNF-Alpha Domain Antibody Construct, CEP-37247/Placulumab,
is as Efficacious as Other Leading TNF-Alpha-Blockade Therapies in a Humanized
Mouse Model of Rheumatoid Arthritis”.
So why stop it? There are already five TNF alpha inhibitors on the
market. But as for the advent of more and more biosimilars, new originator
drugs could find a niche in the market. Too bad, but that’s the way it is.
Links:
Risankizumab (BI-655066)
Risankizumab is a humanized monoclonal antibody that targets IL-23A. Only
two weeks ago an extension phase 2 study
for psoriatic arthritis has been initiated. I had written on risankizumab after
the 2015 ACR Annual Meeting. I had ended then: “So, we have to wait for
Boehringer to sponsor a proper study on psoriatic arthritis.” But now Abbvie is
in charge (AdisInsight). Nothing
on arthritis studies at both the 2016 EULAR and ACR Annual Meetings. My guess
is, that Abbvie / Boehringer will first try to get an approval for psoriasis.
Links:
Ruplizumab (BG9588)
I had a first glimpse of ruplizumab recently. Ruplizumab is a humanized
monoclonal antibody that targets CD40 ligand. AdisInsight lists as most recent
event: “A study has been added to the
adverse events and Transplant Rejection therapeutic trials sections” for August
2001. There had been a safety signal for thromboembolism, so all studies
of had been stopped. Another dead end.
Links:
Sapelizumab
Sapelizumab
is a humanized monoclonal antibody that targets IL-6 receptor. ImMunoGeneTics
(IMGT) lists a phase 3 study for Neuromyelitis optica. There haven’t
been any studies presented at both the 2016 EULAR and ACR Annual Meetings. If
sapelizumab would be a follow-up drug to tocilizumab for Chugai, they should
have started already phase 2 studies by now. So my guess is, we won’t see
sapelizumab in rheumatology.
Links:
Sarilumab
Sarilumab is a human monoclonal antibody that targets IL-6 receptor. My
first blogpost is from 2011. I’ve looked at sarilumab in 22 blogposts. In the
blogpost of 2015 I asked for data on radiographic progression. There had been at the 2016 EULAR Annual Meeting by
D. van der Heijde and colleagues
[SAT0058] to address this topic: “Consistency
of Radiographic Responses with Sarilumab plus Methotrexate across
Subpopulations of Patients with Rheumatoid ArthritisiIn a Phase 3 Study“.
Conclusions:” Sarilumab generally inhibited radiographic
progression to a similar extent across a wide spectrum of subgroups.
Nonetheless, the treatment effect appeared to be greater in subgroups with poor
prognostic markers such as high levels of CRP and more structural damage at
baseline, as well as in nonsmokers and patients with low BMI.” Another study
[SAT0160] looked at clinical and radiographic
outcomes after 2 years. At the 2016 ACR Annual Meeting D. van der Heijde and
colleagues presented the following study [#1633]: “Clinical and Radiographic
Outcomes after 3 Years of Sarilumab in Patients with Rheumatoid
Arthritis“.Conclusions: “Active treatment with sarilumab 200 mg q2w
resulted in durable clinical response and stabilization of radiographic
progression at 3 years irrespective of prior treatment, though the initial
sarilumab 200 mg group showed the most favorable outcomes. Adverse events were
consistent with the anticipated effects of IL-6 inhibition and the known safety
profile of sarilumab”.
However, Sanofi received a formal letter by the end of October tthis year
from the FDA saying it would not be approving the drug because of “certain
deficiencies identified during a routine good manufacturing practice inspection
of the Sanofi Le Trait facility where sarilumab is filled and finished.”
Approval process by EMA has started in August 2016, when Sanofi submitted the
necessary documents.
Links:
DOI: 10.1136/annrheumdis-2016-eular.4363
DOI: 10.1136/annrheumdis-2016-eular.4389
http://acrabstracts.org/abstract/clinical-and-radiographic-outcomesafter-
3-years-of-sarilumab-in-patients-with-rheumatoid-arthritis
Sirukumab (CNTO-136)
Sirukumab (CNTO-136) is a human monoclonal antibody that targets IL-6.
I’ve been following the development of sirukumab since the 2012 EULAR Annual
Meeting in Berlin. In 2015 after the ACR Annual Meeting I asked myself, why
we’d need another anti-IL-6-MAB and why Janssen isn’t pushing to get to the
market. GlaxoSmithKline announced the regulatory submission to EMA seeking
approval of sirukumab for the treatment of adult patients with rheumatoid
arthritis in early September 2016. Janssen Biotech announced seeking approval
of sirukumab for the treatment of adult patients with moderately to severely
active rheumatoid arthritis to the FDA in September 2016. There have been 11
abstracts on sirukuman at the 2016 ACR Annual Meeting. G. Karpouzas and
colleagues presented [#2650]: “Prediction of Inhibition of Radiographic
Progression By Sirukumab, an Anti–IL-6 Cytokine Monoclonal Antibody, in
Patients with Active Rheumatoid Arthritis Despite Disease-Modifying
Anti-Rheumatic Drug Treatment: Results of a Global, Phase 3 Trial”. This phase
3 study showed a significant higher rate of radiographic non-progression with
sirukumab compared to placebo.
Links:
Tildrakizumab
Tildrakizumab is a humanized monoclonal antibody that targets IL-23.
Tildrakizumab demonstrated positive results in phase 3 clinical trials for the
treatment of moderate-to-severe plaque psoriasis. There haven’t
been any studies presented at both the 2016 EULAR and ACR Annual Meetings. But
that doesn’t mean that there won’t be any in the future.
Links:
Toralizumab (IDEC 131)
Toralizumab is a
humanized monoclonal antibody that targets CD40 ligand. Possible indications
include rheumatoid arthritis. As with ruplizumab I had already looked for
information on this MAB. As there had been a safety signal for
thromboembolism, all studies of toralizumab had been stopped. AdisInsight lists
a move by IDEC Pharmaceutical towards the FDA to remove the clinical hold status
on toralizumab in April 2003. Last entry is in August 2004 for a phase 1 study
in Japan. We most probably won’t hear anything on this MAB in the future.
Links:
Tregalizumab (BT-061)
Tregalizumab is a humanised monoclonal antibody that targets CD4. In a
phase 2b study (TREAT 2b) in patients with moderate to severe rheumatoid
arthritis tregalizumab did not meet its primary endpoint. I had become
interested in Tregalizumab at the 2013 ACR Annual Meeting in San Diego; “the
abstract [#1412 – 2015 ACR] informs us of very early data, so I think we have
to wait for more, stressable data”. At the 2015 ACR Annual Meeting Ronald F. van
Vollenhoven and colleagues presented a phase 2b study [#972], which concluded:
“No tested doses of tregalizumab demonstrated significant efficacy improving
signs and symptoms of active RA based on ACR20 responses at wk 12 and 24 despite
dose dependent down-modulation of CD4 expression.” Hence, there haven’t been any new studies at both
the 2016 EULAR and ACR Annual Meetings.
Links:
Vobarilizumab
Vobarilizumab is a humanized monoclonal antibody that targets IL-6
receptor. Only a month ago I’ve written about Vobarilizumab as one of my
readers brought the MAB to my knowledge. Please refer for the discussion on
studies to my blogpost “The Mystery of Vobarilizumab”. Fierce BioTech reports:
“While the ACR data suggest vobarilizumab works, they fall short of showing how
it can take market share from Roche’s rival IL-6 drug.” And: “When paired to
DAS28 data that may favor the use of vobarilizumab over Actemra, Ablynx thinks
these factors amount to a compelling case. The $75 million question is, does
AbbVie agree?” So there’s some kind of suspense about vobarilizumab.
Links:
Zanolimumab
If you look for zanolimumab, you’ll find a study on mycosis fungoides and
Sézary syndrome a study from 2008!). Zanolimumab is a human monoclonal antibody
that targets CD4. Fierce BioTech noted: “Zanolimumab is currently in a Phase
III pivotal study to treat cutaneous T-cell lymphoma (CTCL)”. But I’m more
interested in result concerning rheumatic diseases. There haven’t
been any studies presented at both the 2016 EULAR and ACR Annual Meetings. My
guess is that we won’t see any study in the rheumatologic section.
Links:
Started: 08.12.2016
New entries: 09.12.2016 / 12.12.2016 / 13.12.2016 / 14.12.2016
