Conference call and webcast at 8am
ET
- First therapeutic agent to meet primary
endpoint in a global clinical trial for active lupus nephritis
(LN)
- Voclosporin shown to have statistically
significant improvement in both complete and partial remission in
the presence of forced steroid taper
Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH / TSX:AUP) (“Aurinia”
or the “Company”), a clinical stage biopharmaceutical company
focused on the global immunology market, today announced positive
top-line results from the Phase 2b AURA-LV (AURA) clinical study in
patients with active lupus nephritis (LN). The trial achieved its
primary endpoint, demonstrating statistically significantly greater
complete remission (CR) (as defined by confirmed urinary
protein/creatinine ratio of ≤0.5 mg/mg at 24 weeks and confirmed at
26 weeks) in patients treated with 23.7 mg of voclosporin twice
daily (p=0.045). Both treatment arms, 23.7 mg and 35.9 mg twice
daily also showed a statistically significant improvement in the
rate of achieving partial remission (PR) at 24 weeks (p=0.007;
p=0.024). Each arm of the study included the current standard of
care of mycophenolate mofetil (MMF) as background therapy and a
forced steroid taper to 5 mg/day by week 8 and 2.5 mg by week 16.
No unexpected safety signals were observed and voclosporin was
shown to be well tolerated.
“We are very pleased by these encouraging results and are
grateful to those that participated in our clinical trials,” said
Neil Solomons, M.D., Aurinia’s Chief Medical Officer. “The AURA
study was conducted under rigorous and stringent criteria,
enhancing our confidence in voclosporin’s potential ability to
provide a substantial improvement over the currently accepted
standard of care, especially given that study participants had such
active disease and were exposed to such a low corticosteroid load.
We continue to work diligently towards our goal of improving
long-term outcomes for these patients.”
Based on the results of the 24-week analysis, Aurinia plans to
meet with the U.S. Food and Drug Administration in the fourth
quarter of 2016 to discuss these data and the drug’s subsequent
clinical development and path to registration in LN. Further
analyses of the data will also be conducted and will be released
later this year. Additionally, the Company plans to submit the
results for presentation at a major medical meeting in the near
future. The study will continue through 48 weeks, and these data
will be available for release in early 2017.
Mary Anne Dooley, M.D., a rheumatologist, LN expert and Chief
Investigator on the study, stated “These preliminary results
show great promise and could potentially change the current
treatment paradigm for LN. The remission rates show a meaningful
improvement over the current standard of care. Achieving this
result given the taper to low dose steroids represents a
significant advance. Given the side effects
of corticosteroids, limiting the dose could
substantially enhance a patient’s quality of life.”
“The results of this trial are welcomed and
exciting news for people with lupus and their doctors who are
eager to have more tolerable and effective treatments options,"
said Sandra. C. Raymond, President and Chief Executive
Officer of the Lupus Foundation of America. “Lupus kidney
disease (lupus nephritis) is one of the most serious and
potentially life-threatening complications of this autoimmune
disease, affecting as many as 60 percent of people
with lupus. This trial of voclosporin along
with standard of care is the first trial of a potential
treatment for active lupus nephritis to reach its
primary endpoint, offering hope to individuals
with lupus kidney disease. We look forward to
the timely commencement of a Phase
3 trial; and, should the findings confirm this study, the
addition of this regimen to the arsenal of treatments available to
people who have waited far too long for medicines that improve the
quality of their lives.”
Conference Call and Webcast Details
Aurinia will host a conference call and webcast today, August
15, 2016 at 8:00 a.m. Eastern Daylight Time to discuss the AURA-LV
study results. In order to participate in the conference call,
please dial +1-877-407-9170 (Toll-free US & Canada). An audio
webcast can be accessed under "Webcasts" through the “Investors”
section of the Aurinia corporate website at www.auriniapharma.com.
A replay of the webcast will be available on Aurinia’s website for
45 days.
AURA-LV Trial Design
The AURA–LV study or “Aurinia Urine Protein Reduction in Active
Lupus Nephritis Study” compared the efficacy of voclosporin added
to current standard of care of mycophenolate mofetil (MMF, also
known as CellCept®) against standard of care with placebo in
achieving complete remission (CR) in patients with active LN. It
enrolled 265 patients at centers in over 20 countries worldwide. On
entry to the study, patients were required to have a diagnosis of
LN according to established diagnostic criteria (American College
of Rheumatology) and clinical and biopsy features indicative of
highly active nephritis.
Patients were randomized to one of two dosage groups of
voclosporin (23.7 mg BID and 39.5 mg BID) or placebo, with all
patients also receiving mycophenolate mofetil and oral
corticosteroids as background therapy. All patients had an initial
IV dose of steroids (500-1000 mg) and then were started on 20-25
mg/daily, which was tapered down to a low dose of 5 mg daily by
week 8 and 2.5 mg daily by week 16.
The primary endpoint was a measure of the number of patients who
achieved CR at 24 weeks (confirmed at 26 weeks); CR was defined as
a protein/creatinine ratio of ≤0.5 mg/mg as well as normal stable
renal function (eGFR ≥60 mL/min/1.73m2 or no confirmed decrease
from baseline in eGFR of ≥20%.).
Secondary endpoints included durability of remission, CR as per
the primary analysis at 48-weeks and extra-renal lupus activity
(SLEDAI), which will be evaluated and reported at a later date.
Summary of Results
The groups were generally well-balanced for age, gender and
race, however when considered together, the proteinuria and GFR
data suggest that disease severity was greater for the low-dose
voclosporin group.
Efficacy
- The primary endpoint of CR was met for
the low-dose voclosporin group in the ITT analysis (p=0.045). 32.6%
of patients on low dose achieved CR, compared to 27.3% on high dose
and 19.3% in the control arm.
- The odds ratio indicates that patients
were twice as likely to achieve CR at 24 weeks compared to the
control arm (OR=2.03).
- The primary endpoint was re-analyzed
using the 24-hour urine data in place of First Morning Void (FMV)
collections, confirming the finding that patients were twice as
likely to achieve CR at 24 weeks compared to the control arm
(p=0.047; OR=2.12).
- Both voclosporin groups had a
significantly faster time to CR (UPCR ≤ 0.5 mg/mg) than the control
arm. Results of time to CR for co-variate analyses were broadly
consistent with overall efficacy rates in those sub-groups.
- The secondary endpoint of PR (50%
reduction in UPCR over baseline) was met for both voclosporin
groups in the ITT analysis with 69.7% of patients on low dose
achieving PR (p=0.007) and 65.9% in the high dose group (p=0.024).
49.4% of patients in the control arm achieved PR.
- Time to PR was similar (4 weeks) in the
two voclosporin groups and was shorter than what was observed in
the control group (6.6 weeks).
Safety
- The overall rate of adverse events
(AEs) was similar across all groups.
- The overall rate of serious adverse
events (SAEs) was higher in both voclosporin groups but the nature
of SAEs is consistent with highly active LN.
- The overall pattern of AEs and SAEs was
consistent with that observed in other LN studies.
- There were 13 deaths across the trial:
(2) in the high-dose voclosporin arm; (10) in the low-dose
voclosporin arm (10); and (1) in the control arm, with the majority
of overall deaths (11/13) occurring in Asia. All deaths were
assessed by the Investigator as being unrelated to study treatment.
No dose relationship was observed for the deaths.
About Lupus Nephritis (LN)
Lupus Nephritis (LN) in an inflammation of the kidney caused by
Systemic Lupus Erythematosus (SLE) and represents a serious
progression of SLE. SLE is a chronic, complex and often disabling
disorder and affects more than 500,000 people in the United States
(mostly women). The disease is highly heterogeneous, affecting a
wide range of organs & tissue systems. It is estimated that as
many as 60% of all SLE patients have clinical LN requiring
treatment. Unlike SLE, LN has straightforward disease outcomes
where an early response correlates with long-term outcomes,
measured by proteinuria. In patients with LN, renal damage results
in proteinuria and/or hematuria and a decrease in renal function as
evidenced by reduced estimated glomerular filtration rate (eGFR),
and increased serum creatinine levels. LN is debilitating and
costly and if poorly controlled, LN can lead to permanent and
irreversible tissue damage within the kidney, resulting in
end-stage renal disease (ESRD), thus making LN a serious and
potentially life-threatening condition.
About Voclosporin
Voclosporin, an investigational drug, is a novel and potentially
best-in-class calcineurin inhibitor (“CNI”) with clinical data in
over 2,000 patients in other indications. Voclosporin is an
immunosuppressant, with a synergistic and dual mechanism of action
that has the potential to improve near- and long-term outcomes in
LN when added to standard of care (MMF). By inhibiting calcineurin,
voclosporin blocks IL-2 expression and T-cell mediated immune
responses. It is made by a modification of a single amino acid of
the cyclosporine molecule which has shown a more predictable
pharmacokinetic and pharmacodynamic relationship, an increase in
potency, an altered metabolic profile, and potential for flat
dosing. The Company anticipates that upon regulatory approval,
patent protection for voclosporin will be extended in the United
States and certain other major markets, including Europe and Japan,
until at least October 2027 under the Hatch-Waxman Act and
comparable laws in other countries.
About Aurinia
Aurinia is a clinical stage biopharmaceutical company focused on
developing and commercializing therapies to treat targeted patient
populations that are suffering from serious diseases with a high
unmet medical need. The company is headquartered in Victoria, BC
and focuses its development efforts globally.
Forward Looking Statements
This press release contains forward-looking statements,
including statements related to Aurinia's regulatory strategy
(including plans to meet with the U.S. Food and Drug Administration
to discuss these data and the voclosporin’s subsequent clinical
development and path to registration in LN), Aurinia's analysis,
assessment and conclusions of the results of the AURA-LV clinical
study, and the efficacy and commercial potential of voclosporin. It
is possible that such results or conclusions may change based on
further analyses of these data. Words such as "plans,"
"intends," “may,” "will," "believe," and similar expressions are
intended to identify forward-looking statements. These
forward-looking statements are based upon Aurinia’s current
expectations. Forward-looking statements involve risks and
uncertainties. Aurinia’s actual results and the timing of events
could differ materially from those anticipated in such
forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, the risk that
Aurinia’s analyses, assessment and conclusions of the results of
the AURA-LV clinical study set forth in this release may change
based on further analyses of such data, and the risk that Aurinia’s
clinical studies for voclosporin may not lead to regulatory
approval. These and other risk factors are discussed under "Risk
Factors" and elsewhere in Aurinia’s Annual Information Form for the
year ended December 31, 2015 filed with Canadian securities
authorities and available at www.sedar.com and on Form 40-F with
the U.S. Securities Exchange Commission and available at
www.sec.gov, each as updated by subsequent filings, including
filings on Form 6-K. Aurinia expressly disclaims any obligation or
undertaking to release publicly any updates or revisions to any
forward-looking statements contained herein to reflect any change
in Aurinia's expectations with regard thereto or any change in
events, conditions or circumstances on which any such statements
are based.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160815005340/en/
Aurinia Pharmaceuticals Inc.Celia Economides, MPH,
917-941-9059Associate VP, IR, Communications &
Advocacyceconomides@auriniapharma.comorRenmark Financial
Communications Inc.Barry
Mirebmire@renmarkfinancial.comorLaura
Welshlwelsh@renmarkfinancial.com416-644-2020 or 514-939-3989