TIDMAZN
RNS Number : 0408T
AstraZeneca PLC
12 November 2019
12 November 2019 07:00 GMT
Anifrolumab demonstrated superiority across multiple efficacy
endpoints
in patients with systemic lupus erythematosus in Phase III TULIP
2 trial
Anifrolumab achieved a statistically significant reduction
in disease activity, a statistically significant reduction in
oral
corticosteroid use and improvement in skin manifestations
AstraZeneca today presented detailed results from the positive
Phase III TULIP 2 trial for anifrolumab, a potential new medicine
for the treatment of moderate to severe systemic lupus
erythematosus (SLE), which demonstrated superiority across multiple
efficacy endpoints versus placebo, with both arms receiving
standard of care.
On the primary endpoint, anifrolumab achieved a statistically
significant and clinically meaningful reduction in disease activity
at week 52, with 47.8% of patients receiving anifrolumab responding
compared with 31.5% of patients on placebo, as measured by the
British Isles Lupus Assessment Group-based Composite Lupus
Assessment (BICLA) composite measure.(1) The positive BICLA result
in TULIP 2 is consistent with results from pre-specified analyses
using the BICLA endpoint in the Phase III TULIP 1(2,3) and the
Phase II MUSE trials.(4)
The TULIP 2 trial also showed statistically significant
differences in multiple secondary endpoints.(1) 51.5% of
anifrolumab patients receiving oral corticosteroids (OCS) greater
than or equal to 10mg achieved a sustained reduction in OCS use
compared with 30.2% of patients on placebo. Additionally, 49% of
patients receiving anifrolumab with moderate to severe skin disease
experienced improved skin manifestations at week 12, the
pre-specified timepoint, compared with 25% of patients receiving
placebo. Skin manifestations were measured by the Cutaneous Lupus
Erythematosus Disease Area and Severity Index (CLASI).
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "There has only been one new medicine approved for
systemic lupus erythematosus in the last 60 years, which is why we
are so excited to see the positive TULIP 2 results. There is now a
strong body of evidence demonstrating the benefit of anifrolumab,
and we look forward to bringing this potential new medicine to
patients with systemic lupus erythematosus as soon as
possible."
Professor Eric F. Morand, Monash University, Australia, and
Principal Investigator on the TULIP 2 trial, said: "Systemic lupus
erythematosus is often difficult to treat, and innovative new
therapies are urgently needed. The TULIP 2 results demonstrated
that, by targeting the type I interferon receptor, anifrolumab
reduces overall disease activity, reduces corticosteroid use and
improves skin manifestations."
Dr. Richard Furie, Chief of the Division of Rheumatology at
Northwell Health, New York, US, and Principal Investigator on the
TULIP 1 trial and the Phase II MUSE trial, said: "The results
across the MUSE and TULIP trials are very important because they
support anifrolumab's potential to address systemic lupus
erythematosus, an often devastating disease that can impact almost
any organ and even lead to long-term organ damage and death."
The TULIP data are being presented at the American College of
Rheumatology (ACR) Annual Meeting 2019 in Atlanta, US. The TULIP 1
data were also published simultaneously in The Lancet
Rheumatology.
As previously disclosed, TULIP 1 did not meet its primary
endpoint based on the SLE Responder Index 4 (SRI4) composite
measure. However, analyses of secondary endpoints show efficacy
consistent with TULIP 2 on BICLA response, reduction in OCS use,
and improvement in skin disease activity.(2,3)
The safety and tolerability findings in TULIP 1 and TULIP 2 were
consistent with the known profile of anifrolumab.(1,2,3) There were
more commonly reported cases of herpes zoster in patients on
anifrolumab (TULIP 1: 5.6% vs.1.6%, TULIP 2: 7.2% vs.1.1%). Most
cases were mild to moderate in severity and all were cutaneous and
resolved with antiviral treatment.
About anifrolumab
Anifrolumab is a fully human monoclonal antibody that binds to
subunit 1 of the type I interferon receptor, blocking the activity
of all type I interferons including IFN-alpha, IFN-beta and
IFN-omega.(4) Type I interferons are cytokines involved in the
inflammatory pathways.(5) Between 60% and 80% of adults with SLE
have an increased type I interferon gene signature, which has been
shown to correlate with disease activity.(5,6)
AstraZeneca acquired global rights to anifrolumab through an
exclusive license and collaboration agreement with Medarex, Inc. in
2004. Medarex was acquired by Bristol-Myers Squibb in 2009.
About TULIP
The pivotal TULIP (Treatment of Uncontrolled Lupus via the
Interferon Pathway) programme includes two Phase III clinical
trials, TULIP 1 and TULIP 2, that evaluated the efficacy and safety
of anifrolumab versus placebo in patients with moderately to
severely active autoantibody-positive SLE who are receiving
standard of care treatment.
TULIP 1 randomised 457 eligible patients (1:2:2) to receive a
fixed-dose intravenous infusion of 150mg anifrolumab, 300mg
anifrolumab, or placebo every four weeks. TULIP 1 assessed the
effect of anifrolumab in reducing disease activity as measured by
the SRI4.
TULIP 2 randomised 365 eligible patients (1:1) to receive a
fixed-dose intravenous infusion of 300mg anifrolumab or placebo
every four weeks. TULIP 2 assessed the effect of anifrolumab in
reducing disease activity as measured by the BICLA.
The SRI4 and the BICLA are both validated composite measures of
SLE disease activity, which have been used as primary endpoints in
Phase III lupus trials.(7) Each contain the same disease activity
assessment tools, British Isles Lupus Assessment Group (BILAG)
index and Systemic Lupus Erythematosus Disease Activity Index 2000
(SLEDAI-2K), but utilise different scoring systems.(7) The BICLA
requires improvement in all organs with disease activity from
baseline, with no new flares. It can capture clinically meaningful
partial improvements within an organ system. The SRI4 requires
complete resolution in a single 'higher weight' lupus symptom or
complete resolution in multiple 'lower weight' lupus symptoms, with
no new flares. It does not require improvement across all affected
organ systems.
In addition to the pivotal Phase III TULIP programme,
anifrolumab is being evaluated in a Phase III long-term extension
trial in SLE and a Phase II trial in lupus nephritis.
About SLE
Systemic lupus erythematosus (SLE) is an autoimmune disease in
which the immune system attacks healthy tissue in the body.(8) It
is a chronic and complex disease with a variety of clinical
manifestations that can impact many organs and can cause a range of
symptoms including pain, rashes, fatigue, swelling in joints, and
fevers.(9) It is associated with a greater risk of death from
causes such as infection and cardiovascular disease.(10) There has
been only one new medicine approved for SLE in the last 60
years.(11)
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal and
Metabolism, and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and follow the
Company on Twitter @AstraZeneca.
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References
1. Morand E, Furie R, Tanaka Y, et al. Efficacy and Safety of
Anifrolumab in Patients with Moderate to Severe Systemic Lupus
Erythematosus: Results of the Second Phase 3 Randomized Controlled
Trial [oral]. Presented at: ACR 2019 Annual Meeting; November 8-13,
2019. Abstract ID: 757228.
https://acrabstracts.org/abstract/efficacy-and-safety-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus-results-of-the-second-phase-3-randomized-controlled-trial/
Accessed: November, 2019.
2. Furie R, Morand E, Bruce I, et al. A Phase 3 Randomized
Controlled Trial of Anifrolumab in Patients With Moderate to Severe
Systemic Lupus Erythematosus. Presented at: ACR 2019 Annual
Meeting; November 8-13, 2019. Abstract ID: 1763.
https://acrabstracts.org/abstract/a-phase-3-randomized-controlled-trial-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus/.
Accessed: October, 2019.
3. Furie R, Morand E, Bruce I, et al. Anifrolumab: Type I
Interferon Inhibitor Anifrolumab in Active Systemic Lupus
Erythematosus (TULIP-1): a Randomised, Controlled Phase 3 Trial,
Lancet Rheumatology 2019; doi.org/10.1016/S2665-9913(19)30076-1.
Accessed November 11, 2019.
4. Furie R, Khamashta M, Merrill J.T, et al. Anifrolumab, an
Anti-Interferon--<ALPHA> Receptor Monoclonal Antibody, in
Moderate--to--Severe Systemic Lupus Erythematosus. Arthritis &
Rheumatology. 2017;69(2);376-386.
5. Lauwerys, B.R., Ducreux J, Houssiau F.A., et al. Type I Interferon Blockade in Systemic Lupus Erythematosus: Where Do We Stand? Rheumatology. 2013;53(8);1369-1376.
6. Crow, M. K., Type I Interferon in the Pathogenesis of Lupus, The Journal of Immunology. 2014;192(12);5459-5468.
7. Mikdashi J, Nived O. Measuring Disease Activity in Adults
with Systemic Lupus Erythematosus: The Challenges of Administrative
Burden and Responsiveness to Patient Concerns in Clinical Research.
Arthritis Research & Therapy 2015;17(1):183.
8. The Lupus Foundation of America. Available at https://resources.lupus.org/entry/what-is-lupus?utm_source=lupusorg&utm_medium=answersFAQ. Accessed November 2019.
9. ACR. Guidelines for Referral and Management of Systemic Lupus
Erythematosus in Adults. American College of Rheumatology Ad Hoc
Committee on Systemic Lupus Erythematosus Guidelines, Arthritis
& Rheumatism. 1999; 42; 1785-1796.
10. Nossent J, Cikes N, Kiss E, et al. Current Causes of Death
in Systemic Lupus Erythematosus in Europe, 2000-2004: Relation to
Disease Activity and Damage Accrual. Lupus.16(5), 309-317.
11. Mahieu M. A., Strand V, Simon Lee S., et al. A Critical
Review of Clinical Trials in Systemic Lupus Erythematosus. Lupus.
2016;25(10);1122-1140.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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