OSAKA, Japan & CAMBRIDGE, Mass. - Tuesday, 07. November 2023
−
The Study Met Its Primary Endpoint with 53.3% and 54.2% of Patients
Treated With TAK-279 (15 mg and 30 mg Respectively) Achieving At Least
an ACR 20 Response Compared to 29.2% in the Placebo Group at Week 12 (p =
0.002)1
− TAK-279 Demonstrated Improvements in Key Secondary
Endpoints and a Safety Profile Consistent with the Phase 2b Psoriasis
Study1
− Takeda Will Initiate Phase 3 Studies in Plaque Psoriasis
in FY23 and Psoriatic Arthritis in FY24, While Exploring TAK-279 in
Systemic Lupus Erythematosus, Inflammatory Bowel Disease and Other
Indications
(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK)
today announced that the company will present positive results from its
randomized, double-blind, placebo-controlled, Phase 2b trial evaluating
TAK-279, an investigational oral allosteric tyrosine kinase 2 (TYK2)
inhibitor with next generation selectivity, in patients with active
psoriatic arthritis. These data (Abstract #L12) will be presented on
Tuesday, November 14 as part of the late-breaking poster session from
9:00 AM - 11:00 AM PT at the American College of Rheumatology (ACR)
Convergence 2023 in San Diego, California.
The study met its
primary endpoint with a statistically significant proportion of
patients, 53.3% (15 mg) and 54.2% (30 mg), treated with TAK-279
achieving at least an American College of Rheumatology 20 (ACR 20)
response compared to 29.2% in the placebo arm at week 12 (p = 0.002).1
The safety and tolerability profile of TAK-279 in the trial was
consistent with that observed in the Phase 2b psoriasis study.1 There
was no statistically significant difference in ACR 20 seen in the
TAK-279 5 mg arm (35.2%) compared to the placebo arm (29.2%).1
“There
remains a critical unmet need for psoriatic arthritis treatment options
that not only improve the signs and symptoms of the condition, but are
well tolerated and convenient for patients,” said Alan Kivitz, MD, MACR,
the study’s principal investigator. “As psoriatic arthritis is a
condition with diverse presentations of inflammation and skin
involvement, the improvements seen with just 12 weeks of treatment in
this Phase 2b study in patients with a low mean baseline C-reactive
protein level are particularly encouraging. These results support the
continued evaluation, across the psoriatic arthritis disease spectrum,
of TAK-279, a once-daily oral TYK2 inhibitor with next generation
selectivity.”
The study also demonstrated improvements in key secondary endpoints:
At 15 mg and 30 mg of TAK-279, 26.7% (p=0.005) and 26.4% (p=0.009) of
patients achieved ACR 50 response compared to 9.7% of patients on
placebo.1
A numerically higher proportion of patients treated
with TAK-279 15 mg (14.7%) and 30 mg (13.9%) achieved ACR 70 compared to
those on placebo (5.6%).1
In patients with a body surface area
(BSA) greater than or equal to 3% at baseline, Psoriasis Area and
Severity Index (PASI) 75 was achieved in a greater proportion of
patients treated with TAK-279 (45.7% [30 mg], 28.3% [15 mg] and 25.6% [5
mg]; p = 0.002, 0.101 and 0.186 vs placebo [15.4%]).1
In
patients with Physician Global Assessment of Psoriasis (PGA-PsO) ≥2 at
baseline, a greater proportion of patients treated with TAK-279 30 mg
achieved a PGA-PsO score of 0 (clear) or 1 (almost clear) and at least a
2-point improvement from baseline compared to placebo (32.8% [30 mg],
20.6% [15 mg], 20.4% [5 mg] vs. 15.8% [placebo]; p = 0.034 for 30 mg).2
Reductions were observed in mean change from baseline in the tender
joint count and swollen joint count in all groups, with higher
reductions with the 15 mg and 30 mg doses compared to placebo and 5 mg
TAK-279.1
Minimal disease activity (MDA) response rates were
higher in TAK-279 15 mg and 30 mg groups than in placebo (28.0% [15 mg]
and 29.2% [30 mg]; p = 0.017 and 0.014 vs. placebo [12.5%]).2
The
most common treatment-emergent adverse events (TEAEs) in patients who
received TAK-279 5 mg, 15 mg, or 30 mg versus placebo, respectively,
were nasopharyngitis (8.5%, 9.3%, 9.7%, 4.2%), upper respiratory tract
infections (11.3%, 4%, 9.7%, 2.8%), headache (2.8%, 8.0%, 5.6%, 4.2%)
and rash (4.2%, 8%, 5.6%, 0%).1 No opportunistic infections, major
adverse cardiovascular events or differences in mean laboratory
parameters of interest were observed, compared with placebo. There was
no clinically significant difference in adverse event rates between
doses of TAK-279. Serious and grade 3 or higher TEAEs occurred
infrequently and at a similar rate in the TAK-279 and placebo groups.1
“Based
on these promising efficacy and safety results, achieved at 12 weeks,
we plan to initiate a Phase 3 study of TAK-279 in psoriatic arthritis as
well as commence a Phase 3 study in plaque psoriasis,” said Andy Plump,
President, Research & Development, Takeda. “We are also advancing
the development of TAK-279 in Crohn’s disease, ulcerative colitis and
systemic lupus erythematosus and exploring a range of other potential
indications. These opportunities are being explored in parallel with the
psoriasis and psoriatic arthritis programs.”
About TAK-279
TAK-279
is a highly selective, oral allosteric tyrosine kinase 2 (TYK2)
inhibitor in late-stage development,3 with approximately 1.3
million–fold greater selectivity for TYK2 as compared with JAK1.4
TAK-279 has the potential to become an important treatment option in
multiple immune-mediated inflammatory diseases. In Phase 1 studies,
TAK-279 showed a good tolerability profile, a dose-dependent trend in
exploratory clinical activity and a pharmacokinetic profile allowing for
once-daily solid oral dosing.5 In a Phase 2b study in patients with
moderate-to-severe psoriasis, a statistically significant greater
proportion of patients receiving TAK-279 achieved Psoriasis Area and
Severity Index (PASI) 75, 90 and 100 in the 5mg, 15mg and 30mg dosing
arms compared to placebo at 12 weeks.3 TAK-279 is an investigational
compound that has not been approved for use by any regulatory authority.
About the TAK-279 Phase 2b Study in Psoriatic Arthritis
The
Phase 2b study (NCT05153148) is a randomized, multicenter,
double-blind, placebo-controlled multiple-dosed trial designed to
evaluate the efficacy, safety and tolerability of TAK-279 in patients
with active psoriatic arthritis.6 Eligible patients were aged ≥ 18
years, with psoriatic arthritis symptoms for ≥ 6 months prior to
screening, met Classification criteria for Psoriatic Arthritis (CASPAR),
and had ≥ 3 tender and ≥ 3 swollen joint counts (TJC/SJC) at enrollment
despite prior NSAID, DMARD or biologic treatment.6 In total, 290
patients were randomized and treated (1:1:1:1 ratio) to receive one of
three doses of TAK-279 or placebo once daily for 12 weeks with a 4 week
safety follow up period; 245 completed 12 weeks’ treatment.1,6 Baseline
characteristics were generally comparable across groups (except for a
lower mean TJC in the 30 mg group); 58.6% had BSA ≥ 3% (of which mean
baseline PASI score was 6.2), and 32.1% had prior biologic use (20.7%
TNFis).1 Mean baseline high-sensitivity C-reactive protein (hsCRP) was
7.0 mg/L; 45.9% had hsCRP ≥ 3 mg/L.1 The primary endpoint was the
proportion of patients achieving at least an ACR 20 response at week
12.6
The ACR 20, ACR 50, and ACR 75 are composite measures
defined as 20%, 50% and 75% improvement, respectively, in the number of
tender and number of swollen joints, and in three of the following five
criteria: patient global assessment of psoriatic arthritis, physician
global assessment of psoriatic arthritis, patient pain scale, disability
history questionnaire and an acute phase reactant.6
The
Psoriasis Area and Severity Index (PASI) is a scoring system to evaluate
baseline and response of therapy in psoriasis. PASI 75 is a binary
outcome that indicates a 75% or greater improvement in PASI from
baseline.7
About Psoriatic Arthritis
Psoriatic arthritis is a
chronic immune-mediated inflammatory disease, characterized by
inflammation causing joint pain, stiffness, and swelling and occurs with
the skin condition psoriasis.8 Psoriatic arthritis affects
approximately 10 million people globally.9 Psoriatic arthritis is a
heterogenous condition - affecting everyone differently.10 Symptoms may
be mild or severe, affect just a few or many joints, and symptoms can
come and go.10 Chronic inflammation seen in psoriatic arthritis may
result in irreversible joint damage if not managed appropriately.8
Progressive disease is associated with substantial physical disability11
and significant mental health disorders, such as anxiety and
depression.12
About Tyrosine Kinase 2 (TYK2) Inhibitors
Tyrosine
kinase 2 (TYK2) is an intracellular enzyme that belongs to the Janus
family of protein tyrosine kinases.13 TYK2 is a member of the Janus
kinase-signal transducer and activator of transcription (JAK-STAT)
signaling pathway, which mediates signaling downstream of key immune
cytokine receptors.13 Inflammatory cytokine signaling is associated with
several immune-mediated inflammatory diseases, including psoriasis,
psoriatic arthritis, systemic lupus erythematosus and inflammatory bowel
disease.14 Selective allosteric inhibition of TYK2 may be a promising
therapeutic approach to target immune-mediated inflammation while
potentially decreasing the risk of JAK-related toxicity.15
About Takeda
Takeda
is focused on creating better health for people and a brighter future
for the world. We aim to discover and deliver life-transforming
treatments in our core therapeutic and business areas, including
gastrointestinal and inflammation, rare diseases, plasma-derived
therapies, oncology, neuroscience and vaccines. Together with our
partners, we aim to improve the patient experience and advance a new
frontier of treatment options through our dynamic and diverse pipeline.
As a leading values-based, R&D-driven biopharmaceutical company
headquartered in Japan, we are guided by our commitment to patients, our
people and the planet. Our employees in approximately 80 countries and
regions are driven by our purpose and are grounded in the values that
have defined us for more than two centuries. For more information, visit
https://www.takeda.com.
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press release contains information about products that may not be
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including the ones under development.
1 TAK-279 PsA Ph2b ACR
abstract (TKPO011). Efficacy and safety outcomes of TAK-279, a selective
oral tyrosine kinase 2 (TYK2) inhibitor, from a randomized,
double-blind, placebo-controlled phase 2b trial in patients with active
psoriatic arthritis. Presented at American College of Rheumatology (ACR)
2023 Convergence, November 10–15, 2023 San Diego, CA, USA.
2 Takeda Pharmaceuticals. Data on File.
3
Armstrong A, Lynde C, Forman S, et al. Efficacy and safety results from
the randomized double-blind, placebo-controlled phase 2b trial of TYK2
inhibitor NDI-034858 in moderate-to-severe psoriasis. Presented March
17-21, 2023, New Orleans, Louisiana at the 2023 American Academy of
Dermatology Annual Meeting.
4 Leit S, J, Greenwood Carriero S, et
al. Discovery of a potent and selective tyrosine kinase two inhibitor:
TAK-279. J Medicinal Chemistry.2023;66(15):10473-10496.
doi.org/10.1021/acs.jmedchem.3c00600.
5 Gangolli EA, Carreiro S,
Leit S, et al. Characterization of pharmacokinetics, pharmacodynamics,
tolerability and clinical activity in Phase 1 studies of the novel
allosteric tyrosine kinase 2 (TYK2) inhibitor NDI-034858. Presented May
18-21, 2022, Portland, OR at the 2022 Society for Investigative
Dermatology Annual Meeting.
6 ClinicalTrials.gov. A Study to
Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in
Subjects With Active Psoriatic Arthritis. Available at:
https://classic.clinicaltrials.gov/ct2/show/NCT05153148. Last accessed:
November 2023
7 Rodgers M, Epstein D, Bojke L, et al. Etanercept,
Infliximab and Adalimumab for the Treatment of Psoriatic Arthritis: A
Systematic Review and Economic Evaluation. Southampton (UK): NIHR
Journals Library; 2011 Feb. (Health Technology Assessment, No. 15.10.)
Appendix 18, Estimation of Psoriasis Area and Severity Index score for
treatment responders in the decision model. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK109508/. Last accessed: November
2023.
8 American College of Rheumatology. Psoriatic Arthritis.
Available at: https://rheumatology.org/patients/psoriatic-arthritis.
Last accessed: November 2023.
9 Scotti L, Franchi M, Marchesoni
A, Corrao G. Prevalence and incidence of psoriatic arthritis: A
systematic review and meta-analysis. Semin Arthritis Rheum. 2018
Aug;48(1):28-34. doi:10.1016/j.semarthrit.2018.01.003.
10
Arthritis Foundation. Psoriatic Arthritis. Available at:
https://www.arthritis.org/diseases/psoriatic-arthritis. Last accessed:
November 2023.
11 Mease P, Strand V, Gladman D. Functional
impairment measurement in psoriatic arthritis: Importance and
challenges. InSeminars in arthritis and rheumatism 2018 Dec 1 (Vol. 48,
No. 3, pp. 436-448). WB Saunders.
12 Zhao SS, Miller N, Harrison
N, Duffield SJ, Dey M, Goodson NJ. Systematic review of mental health
comorbidities in psoriatic arthritis. Clinical Rheumatology. 2020
Jan;39:217-25.
13 Muromoto R, Oritani K, Matsuda T. Current
understanding of the role of tyrosine kinase 2 signaling in immune
responses. World J Biol Chem. 2022;13(1):1–14.
doi:10.4331/wjbc.v13.i1.1.
14 Bunte K et al. Th17 Cells and the
IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune
Mediated Inflammatory Diseases. 2019 Intl J Molecular Sci.
15
Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus
kinase‒signal transducer and activator of transcription signaling and
inhibition in plaque psoriasis. J Am Acad Dermatol. 2022;86(1):148-157.
doi:10.1016/j.jaad.2021.06.869..
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Contacts
Media Contacts:
Japanese Media
Jun Saito
jun.saito@takeda.com
U.S. and International Media
Mark Dole
mark.dole@takeda.com
+1 (857) 352-6349
Investor Relations
Christopher O’Reilly
christopher.oreilly@takeda.com
+81 (0) 3-3278-2543
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