Tanezumab in Patients with Knee or Hip Osteoarthritis at the 2017 ACR Annual Meeting in San Diego

You might recall that I had been very critical about tanezumab in osteoarthritis [1]. There has been one abstract/poster on tanezumab at the 2017 ACR Annual Meeting in San Diego. Let’s have a closer look!

C.A. Birbara and colleagues presented [2]: “Efficacy and Safety of Subcutaneous Tanezumab in Patients with Knee or Hip Osteoarthritis (NCT01089725)”. The authors concluded: “SC TNZ [subcutaneous tanezumab] provided improvements in Pain, Physical Function, and PGAOA [Patient’s Global Assessment of Osteoarthritis] at all doses. Efficacy and safety of SC TNZ were generally similar to IV [intravenous] in patients with OA [osteoarthritis] pain.”

If you look up NCT01089725 [3], you’ll find a study with this title: “Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Of The Analgesic Efficacy And Safety Of Subcutaneous Administration Of Tanezumab In Patients With Osteoarthritis Of The Knee”. Moreover you find this: “This study was terminated on 08 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.” Last update on this study had been on July 3, 2013. Am I missing something?

In the study that C.A. Birbara presented we find under methods: “Patients (N=379) with knee or hip OA were randomized and treated with placebo (n=72), TNZ 2.5 mg SC (n=74), 5 mg SC (n=63), 10 mg SC (n=86) or 10 mg IV (n=84) every 8 weeks.” In Clinical Trials we find: “Actual Enrollment: 385 participants”. Do we look at hitherto unpublished data of an older study? I’m growing even more skeptical about tanezumab.

So, we’ve got some patient-reported outcome measures. Where are structural outcome measures? Why aren’t we told if tanezumab is better than naproxen, celecoxib, or oxycodone?

Until further notice I’ll stay skeptical about tanezumab in osteoarthritis.

Links: 

[1] http://rheumatologe.blogspot.de/2015/12/tanezumab-in-osteoarthritis-at-acr-2015.html

[2] Birbara CA, Dabezies EJ, Burr AM, Fountaine RJ, Smith MD, Brown MT, West CR, Arends RH, Verburg KM. Efficacy and Safety of Subcutaneous Tanezumab in Patients with Knee or Hip Osteoarthritis (NCT01089725) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-subcutaneous-tanezumab-in-patients-with-knee-or-hip-osteoarthritis-nct01089725/. Accessed March 16, 2018.

[3] https://clinicaltrials.gov/ct2/show/NCT01089725

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Bimekizumab at the 2017 ACR Annual Meeting in San Diego

Bimekizumab (alternative names: CDP-4940 and UCB-4940) is a monoclonal antibody that targets IL-17A and IL-17F. Bimekizumab is developed by UCB. Adis insight mentions a phase 3 study for psoriatic arthritis [1]. In 2018 the phase 3 study (BE READY) for plaque psoriasis has been initiated in the USA (NCT03410992): another phase 3 study (BE SURE / NCT03412747) is under plan.

Bimekizumab has been launched with two studies at the 2017 ACR Annual Meeting in San Diego.

A. Maroof and colleagues presented [2]: “Bimekizumab Dual Inhibition of IL-17A and IL-17F Provides Evidence of IL-17F Contribution to Chronic Inflammation in Disease-Relevant Cells”. The authors concluded: “Dual neutralization of IL-17A and IL-17F provides evidence for the contribution of IL-17F to inflammation in joints and skin beyond IL-17A alone. Dual inhibition of IL-17A and IL-17F by bimekizumab may provide an effective treatment for immune-mediated inflammatory diseases such as PsA [psoriatic arthritis].” Nice to know, but …

M. Shah and colleagues elucidated us on [3]: “Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling”. The authors concluded: “These data show that both IL-17A and IL-17F enhance in vitro osteogenic differentiation and bone formation […], hence inhibition of both IL-17A and IL-17F with bimekizumab offers an attractive therapeutic strategy to prevent this debilitating feature of SpA [spondyloarthritis].” Also nice to know, but …

Secukinumab (Cosentyx, a human IgG1κ MAB that binds to the protein interleukin IL-17A), brodalumab (Siliq in the US, Kyntheum in Europe, a human MAB that binds to the IL-17-receptor), and ixekizumab (Taltz, a humanized MAB binding to IL-17) are already out on the market. I’m not sure, what UCB is doing. I remember UCB attending the industry exhibition ofan Annual Meetings of ACR or EULAR with an empty information stall, as certolizumab hasn’t been approved in time. Is UCB slowing down, because the market already has been split up? The two studies are perfectly O.K., but not coming up with a phase 1 or 2 study at the 2017 ACR Annual Meeting must be called lack of commitment.

Links and References:

[1] http://adisinsight.springer.com/drugs/800037676

[2] Maroof A, Okoye R, Smallie T, Baeten D, Archer S, Simpson C, Griffiths M, Shaw S. Bimekizumab Dual Inhibition of IL-17A and IL-17F Provides Evidence of IL-17F Contribution to Chronic Inflammation in Disease-Relevant Cells [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/bimekizumab-dual-inhibition-of-il-17a-and-il-17f-provides-evidence-of-il-17f-contribution-to-chronic-inflammation-in-disease-relevant-cells/. Accessed March 8, 2018.

[3] Shah M, Maroof A, Al-Hosni R, Gikas P, Gozzard N, Shaw S, Roberts S. Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/bimekizumab-blocks-t-cell-mediated-osteogenic-differentiation-of-periosteal-stem-cells-coupling-pathological-bone-formation-to-il-17a-and-il-17f-signaling/. Accessed March 8, 2018.

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Guselkumab at the 2017 ACR Annual Meeting in San Diego

Guselkumab is a monoclonal antibody that targets the p19 subunit of IL-23. Guselkumab is marketed by Janssen-Cilag under the name of TREMFYA^® [maybe Xzkrkplk would have been easier to memorize]. The FDA approved TREMFYA™ (guselkumab) for the treatment of moderate to severe plaque psoriasis in July 2017 [1] and the EMA did equally in November 2017 [2].

Guselkumab showed up at the 2017 ACR Annual Meeting in San Diego with just one study [3].

A.A. Deodhar and colleagues presented a phase 2a study: “Efficacy and Safety Results of Guselkumab in Patients with Active Psoriatic Arthritis over 56 Weeks from a Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study.” The authors concluded: “In pts [patients] with active PsA [psoriatic arthritis] and ≥3% BSA [body surface area] of psoriasis, GUS [guselkumab] demonstrated substantial benefits on joint symptoms, physical function, psoriasis, enthesitis, dactylitis, and quality of life, and efficacy was well-maintained through wk56 [week 56]. GUS was well-tolerated with no unexpected safety findings in this population after ~1 year of exposure.”

This study tells us that we might have a new drug against psoriatic arthritis and maybe then also against ankylosing spondylitis within a couple of years. There have to be some more phase 3 studies in arthritis ans spondyloarthritis before getting approval by FDA and EMA. I don’t think that Janssen-Cilag will not try to get approval for the treatment of psoriatic arthritis and ankylosing spondylitis.

Links and References:

[1] https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis

[2] https://www.presseportal.de/pm/16998/3795787

[3] Deodhar AA, Gottlieb AB, Boehncke WH, Dong B, Wang Y, Zhuang Y, Barchuk W, Xu XL, Hsia E. Efficacy and Safety Results of Guselkumab in Patients with Active Psoriatic Arthritis over 56 Weeks from a Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-results-of-guselkumab-in-patients-with-active-psoriatic-arthritis-over-56-weeks-from-a-phase-2a-randomized-double-blind-placebo-controlled-study/. Accessed March 8, 2018.

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Risankizumab at the 2017 ACR Annual Meeting in San Diego

Risankizumab is a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit. It is also called BI 655066 or ABBV-066. There are quite a lot of competing compounds targeting IL-23 or IL-17 to treat psoriasis and psoriatic arthritis [PsA]. The market for psoriatic arthritis is much smaller than for rheumatoid arthritis, but any new drug is welcome, because some patients who do not get better on a galore of drugs will just do fine on the next biologic. Risankizumab is tested in Crohn's disease, psoriasis, and psoriatic arthritis [1].

K.A. Papp and colleagues published this study [2] in the New England Journal of Medicine: “Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis”. They could conclude: “In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. […]”

Risankizumab appeared at the 2017 ACR Annual Meeting in San Diego with just one study in the late breaking section. P.J. Mease and colleagues presented [3]: “Efficacy and Safety Results from a Phase 2 Trial of Risankizumab, a Selective IL-23p19 Inhibitor, in Patients with Active Psoriatic Arthritis”. Patients were stratified into groups of 20-40 to look at different dosages of risankizumab (RZB). “ACR20 responses were significantly greater in pts receiving RZB (across all arms, 57.1–65.0%) compared with PBO (37.5% …)”. Conclusion: “In this Phase 2 study, RZB significantly improved joint and skin symptoms in pts with active PsA. RZB was well-tolerated with no new or unexpected safety findings.”

It doesn’t mean that we have a new drug, but in a few years we might have a new drug against psoriatic arthritis and maybe then also against ankylosing spondylitis. There have to be some phase 3 studies before getting approval by FDA and EMA, but my guess is that AbbVie is planning to go for approval of risankizumab in different indications. Let’s wait.

 

 

Links:

[1] https://www.abbvie.com/our-science/pipeline/risankizumab.html 

[2] http://www.nejm.org/doi/full/10.1056/NEJMoa1607017

[3] Mease PJ, Kellner H, Morita A, Kivitz AJ, Papp KA, Aslanyan S, Berner B, Chen K, Eldred A, Behrens F. Efficacy and Safety Results from a Phase 2 Trial of Risankizumab, a Selective IL-23p19 Inhibitor, in Patients with Active Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-results-from-a-phase-2-trial-of-risankizumab-a-selective-il-23p19-inhibitor-in-patients-with-active-psoriatic-arthritis/. Accessed March 8, 2018.

[4] https://www.ncbi.nlm.nih.gov/pubmed/26080615  

 

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