EASI-Related and PASI-Related Clinical
Efficacy Endpoints in Atopic Dermatitis and Psoriasis Studies Were
Incorrectly Calculated by Lilly and Were Reported Erroneously at
EADV 2022
SAN
FRANCISCO, Aug. 7, 2023 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced that efficacy data
previously generated by Eli Lilly & Company for
rezpegaldesleukin (REZPEG) that were presented at the September 2022 EADV Congress were incorrectly
calculated by Lilly. The erroneous data is from two Phase
1b studies for REZPEG that were
conducted by Lilly. The new and corrected data highlight the
important potential of REZPEG to help patients battling atopic
dermatitis (AtD), a chronic skin condition that afflicts nearly 10%
of Americans.
Specifically, the new and corrected data from the atopic
dermatitis study demonstrate that 12 weeks of REZPEG
therapy at the highest dose resulted in a mean Eczema Area and
Severity Index (EASI) score improvement of 83% with a p-value of
0.002 as compared to placebo and an EASI-75 response rate of 41%
(see corrected data found in Tables 1 and 2 below). REZPEG also
provided a more rapid and steep drop in EASI scores immediately
after therapy initiation than the previously reported erroneous
data indicated. This efficacy benefit was also maintained for 36
weeks without additional treatment after the 12-week induction
period.
Nektar discovered the EASI-related and Psoriasis Area and
Severity Index (PASI)-related clinical efficacy endpoints were
incorrectly calculated by Lilly after all rights to REZPEG
were returned to Nektar and the raw data files from the REZPEG
clinical studies were transferred to Nektar. This transfer of the
raw data files to Nektar was the first opportunity for Nektar to
review the complete patient data files. Subsequently, an
independent statistical firm was employed to analyze the raw data
de-novo, and the firm provided the new and corrected data in
the tables below.
The internal statistical and clinical teams in charge of the two
studies at Lilly were made aware that
Nektar discovered the data errors. Lilly confirmed
the errors in written communications with Nektar.
"These corrected data importantly demonstrate that REZPEG, a
novel and differentiated T regulatory cell mechanism, holds great
promise for treating patients with atopic dermatitis," said
Howard W. Robin, President & CEO
of Nektar Therapeutics. "The data further reinforce the importance
of Nektar's renewed strategic focus on advancing REZPEG into a
robust Phase 2b study in
biologic-naïve patients with moderate to severe atopic dermatitis
by October of this year."
Hyperlink to Supporting Slide Set
SECTION A: Corrected efficacy endpoints for the Phase
1b study in atopic
dermatitis
TABLE
1:
|
Study
Arm
|
EADV 2022
INCORRECT
INTERIM DATA
REPORTED1
Mean %
improvement
in EASI score
from baseline
at 12-weeks
|
p-value
|
CORRECTED
INTERIM DATA
(INDEPENDENT
STATISTICAL
AUDIT)
Mean %
improvement in
EASI score
from baseline
at 12-weeks
|
p-value
|
Placebo
|
49
|
|
47
|
|
12
µg/kg
|
53
|
NS
|
65
|
NS
|
24
µg/kg
|
66
|
NS
|
83
|
0.002
|
TABLE
2:
|
Study
Arm
|
EADV 2022
INCORRECT
INTERIM DATA
REPORTED1
Proportion of
Patients
Who Achieved an
EASI-75 Score (NRI
calculation)
|
CORRECTED
INTERIM
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of
Patients
Who Achieved an
EASI-75 Score (NRI
calculation)
|
CORRECTED
INTERIM
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of
Patients
Who Achieved an
EASI-75 Score (as observed)
|
Placebo
|
20 %
|
20 %
|
29 %
|
12
µg/kg
|
25 %
|
25 %
|
33 %
|
24
µg/kg
|
29 %
|
41 %
|
58 %
|
Note: Corrected results utilize a 72-point EASI scale,
and all patient data were included in the analyses. The continuous
endpoint of % improvement in EASI score from baseline is calculated
from observed data using a mixed model for repeated measures (MMRM)
as specified in the statistical analysis plan (SAP) defined in the
protocol. All statistical analyses on the efficacy endpoints are
post-hoc exploratory per the SAP.
SECTION B: Corrected efficacy endpoints for the Phase
1b study in psoriasis:
TABLE
3:
|
Study
Arm
|
EADV 2022
INCORRECT
FINAL DATA
REPORTED2
LS
Mean
% improvement in
PASI score from
baseline at 12-
weeks (as
observed)
|
p-value
|
CORRECTED
FINAL DATA
(INDEPENDENT
STATISTICAL
AUDIT)
LS
Mean
% improvement in
PASI score from
baseline at 12-
weeks (as
observed)
|
p-value
|
Placebo
|
19
|
NS
|
24
|
NS
|
24
µg/kg
|
40
|
NS
|
44
|
NS
|
TABLE
4:
|
Study
Arm
|
EADV 2022
INCORRECT
FINAL DATA
REPORTED2
Proportion of Patients
Who Achieved a PASI-50
Score (NRI)
|
CORRECTED FINAL
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of Patients
Who Achieved a PASI-50
Score (NRI)
|
CORRECTED
INTERIM
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of
Patients
Who Achieved a PASI-50
Score (as observed)
|
Placebo
|
20 %
|
20 %
|
20 %
|
24
µg/kg
|
26 %
|
32 %
|
55 %
|
TABLE
5:
|
Study
Arm
|
EADV 2022
INCORRECT
FINAL DATA
REPORTED2
Proportion of Patients
Who Achieved a PASI-75
Score (NRI)
|
CORRECTED
FINAL
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of Patients
Who Achieved a PASI-75
Score (NRI)
|
CORRECTED
INTERIM
DATA (INDEPENDENT
STATISTICAL AUDIT)
Proportion of
Patients
Who Achieved a PASI-75
Score (as observed)
|
Placebo
|
0
|
0
|
0
|
24
µg/kg
|
11 %
|
21 %
|
36 %
|
|
Note:
Corrected results utilize a 72-point PASI scale. The continuous
endpoint of % improvement in PASI score from baseline is calculated
from observed data using a mixed model for repeated measures (MMRM)
as specified in the SAP defined in the protocol. All statistical
analyses on the efficacy endpoints are post-hoc exploratory per the
SAP.
|
The two double-blind, randomized, placebo-controlled studies of
REZPEG evaluated safety, tolerability, and pharmacokinetics over a
12-week induction treatment period. Patients were followed for an
additional 36 weeks after the end of the treatment period. The
first study enrolled 44 patients with moderate-to-severe AtD who
had progressed on topical corticosteroids and the second study
enrolled 26 patients with plaque psoriasis who were candidates for
systemic therapy or phototherapy.
For the AtD study, efficacy endpoints related to the Eczema Area
and Severity Index (EASI), at an interim data cut-off date, were
miscalculated for the validated 72-point EASI scoring system
and excluded certain available patient data at the time of the
interim. The EASI is a validated and widely used tool in
atopic dermatitis studies that was clearly outlined in the REZPEG
protocol. The EASI measures the severity of AtD for patients
and scoring ranges from 0 (no disease) to 72 (maximal
disease)3. The corrected and audited interim data
analyses for the atopic dermatitis study utilizes the validated
72-point EASI scoring system and includes all patients in the
12-week induction period enrolled in the Phase 1b study.
For the psoriasis study, efficacy endpoints related to the
Psoriasis Area and Severity Index (PASI), at the final data cut-off
date, were miscalculated for the validated 72-point PASI
scoring system. The PASI is a validated and widely used tool
to measure the severity of psoriasis plaques for patients and
scoring ranges from 0 (no disease) to 72 (maximal
disease)4. The corrected and audited final data analyses
for the psoriasis study utilizes the validated 72-point PASI
scoring system from the Phase 1b
study.
Nektar plans to hold an investor meeting with key opinion
leaders in the coming weeks to discuss these corrected data as well
as new and final data for the 36-week follow-up period for REZPEG.
The final data strengthen the potential for REZPEG to provide a
remittive effect. Nektar will also announce the new study design
for the Phase 2b study of REZPEG in
biologic-naïve patients with moderate to severe atopic dermatitis
who have progressed on topical corticosteroids. This study is
planned to start in October of this year.
Conference Call to Discuss Second Quarter 2023 Financial
Results
Nektar management will host a conference call to discuss this
press release and announce its financial results for the second
quarter 2023 on Tuesday, August 8,
2023, beginning at 5:00 p.m. Eastern
Time/2:00 p.m. Pacific
Time.
This press release and live audio-only webcast of the conference
call can be accessed through a link that is posted on the Home Page
and Investors section of the Nektar website: http://ir.nektar.com/.
The web broadcast of the conference call will be available for
replay through September 8, 2023.
To access the conference call, please pre-register at Nektar
Earnings Call Registration. All registrants will receive dial-in
information and a PIN allowing them to access the live call.
About REZPEG
Autoimmune and inflammatory diseases
cause the immune system to mistakenly attack and damage healthy
cells in a person's body. A failure of the body's self-tolerance
mechanisms enables the formation of the pathogenic T lymphocytes
that conduct this attack. REZPEG is a potential first-in-class
resolution therapeutic that may address this underlying immune
system imbalance in people with many autoimmune and inflammatory
conditions. It targets the interleukin-2 receptor complex in the
body in order to stimulate proliferation of powerful inhibitory
immune cells known as regulatory T cells. By activating these
cells, REZPEG may act to bring the immune system back into
balance.
REZPEG is being developed as a self-administered injection for a
number of autoimmune and inflammatory diseases. It is wholly-owned
by Nektar Therapeutics.
About Nektar Therapeutics
Nektar Therapeutics is a
biopharmaceutical company with a robust, wholly owned R&D
pipeline of investigational medicines in immunology and oncology as
well as a portfolio of approved partnered medicines. Nektar is
headquartered in San Francisco,
California, with additional manufacturing operations in
Huntsville, Alabama. Further
information about the company and its drug development programs and
capabilities may be found online at http://www.nektar.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can
be identified by words such as: "will," "may," "advance,"
"develop," "provide," "potential" and similar references to future
periods. Examples of forward-looking statements include, among
others, statements regarding the therapeutic potential of, and
future development plans for rezpegaldesleukin, and our other drug
candidates in research programs, the prospects and plans for our
collaborations with other companies, the timing of the initiation
of clinical studies and the data readouts for our drug candidates.
Forward-looking statements are neither historical facts nor
assurances of future performance. Instead, they are based only on
our current beliefs, expectations and assumptions regarding the
future of our business, future plans and strategies, anticipated
events and trends, the economy and other future conditions. Because
forward-looking statements relate to the future, they are subject
to inherent uncertainties, risks and changes in circumstances that
are difficult to predict and many of which are outside of our
control. Our actual results may differ materially from those
indicated in the forward-looking statements. Therefore, you should
not rely on any of these forward-looking statements. Important
factors that could cause our actual results to differ materially
from those indicated in the forward-looking statements include,
among others: (i) our statements regarding the therapeutic
potential of rezpegaldesleukin, and our other drug candidates are
based on preclinical and clinical findings and observations and are
subject to change as research and development continue; (ii)
rezpegaldesleukin and our other drug candidates are investigational
agents and continued research and development for these drug
candidates is subject to substantial risks, including negative
safety and efficacy findings in ongoing clinical studies
(notwithstanding positive findings in earlier preclinical and
clinical studies); (iii) rezpegaldesleukin and our other drug
candidates are in various stages of clinical development and the
risk of failure is high and can unexpectedly occur at any stage
prior to regulatory approval; (iv) the timing of the commencement
or end of clinical trials and the availability of clinical data may
be delayed or unsuccessful due to challenges caused by the COVID-19
pandemic, regulatory delays, slower than anticipated patient
enrollment, manufacturing challenges, changing standards of care,
evolving regulatory requirements, clinical trial design, clinical
outcomes, competitive factors, or delay or failure in ultimately
obtaining regulatory approval in one or more important markets; (v)
we may not achieve the expected cost savings we expect from our
2022 corporate restructuring and reorganization plan or our 2023
cost restructuring plan and we may undertake additional
restructuring and cost-saving activities in the future, (vi)
patents may not issue from our patent applications for our drug
candidates, patents that have issued may not be enforceable, or
additional intellectual property licenses from third parties may be
required; and (vii) certain other important risks and uncertainties
set forth in our Annual Report on Form 10-Q filed with
the Securities and Exchange Commission on May 10,
2023. Any forward-looking statement made by us in this press
release is based only on information currently available to us and
speaks only as of the date on which it is made. We undertake no
obligation to update any forward-looking statement, whether written
or oral, that may be made from time to time, whether as a result of
new information, future developments or otherwise.
Contacts:
For Investors:
Vivian Wu of Nektar Therapeutics
(628) 895-0661
For Media:
Chris
Kittredge/Columbia Clancy/Michelle
Van Wyk
FGS Global
Nektar@fgsglobal.com
1.
|
Schleicher et. al.:
"Efficacy and Safety of a Selective Regulatory T-Cell Inducing
IL-2 Conjugate (LY3471851) in the Treatment of Atopic Dermatitis: A
Phase 1 Randomised Study"
|
2.
|
Forman et. al:
"Efficacy and Safety of a Selective Regulatory T-Cell Inducing
IL-2 Conjugate (LY3471851) in the Treatment of Psoriasis: A Phase 1
Randomised Study"
|
3.
|
Hanifin, J. M.;
Thurston, M.; Omoto, M.; Cherill, R.; Tofte, S. J.; Graeber, M.
(2001). "The eczema area and severity index (EASI): assessment of
reliability in atopic dermatitis. EASI Evaluator
Group". Experimental Dermatology. 10 (1):
11–18. doi:10.1034/j.1600-0625.2001.100102.x. PMID 11168575. S2CID 25864663.
|
4.
|
https://doi.org/10.5070/D318w9j736
|
View original content to download
multimedia:https://www.prnewswire.com/news-releases/nektar-announces-promising-new-and-corrected-rezpegaldesleukin-efficacy-data-which-were-previously-reported-in-2022-and-incorrectly-calculated-by-former-collaborator-eli-lilly--company-301894443.html
SOURCE Nektar Therapeutics