Conference call and webcast to be held today
at 8:00 a.m. Eastern Time
SOUTH
SAN FRANCISCO, Calif., June 8, 2022
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL)
today announced top-line efficacy and safety data from the FORWARD
Phase 3 clinical trial, a global, multi-center, randomized,
double-blind, placebo-controlled trial of fostamatinib in patients
with warm autoimmune hemolytic anemia (wAIHA). The trial did
not demonstrate statistical significance in the primary efficacy
endpoint of durable hemoglobin response in the overall study
population. In a post-hoc regional analysis of U.S., Canadian,
Australian, and Western European trial sites, patients treated with
fostamatinib had a favorable durable hemoglobin response compared
to placebo, whereas in the Eastern European trial sites patients
did not. Rigel plans to continue analyzing the data to
understand the geographical differences in patient disease
characteristics and outcomes and discuss these findings with the
U.S. Food and Drug Administration (FDA).
The safety and tolerability profile in the FORWARD trial was
consistent with the existing fostamatinib safety database.
Efficacy Results:
The trial includes 90 patients in
three pre-specified geographic regions, 14 sites in the U.S.,
Canada, and Australia; 16 sites in Western Europe (Austria, Germany, Spain, France, Italy, Belgium, U.K., Netherlands, Norway); and 16 sites in Eastern Europe (Bulgaria, Czech
Republic, Russia,
Ukraine, Georgia, Belarus, Serbia). Patients were randomized 1:1
to receive fostamatinib or matching placebo twice daily for 24
weeks. The primary efficacy endpoint of durable hemoglobin (Hgb)
response was defined as achieving a Hgb ≥10 g/dL with an increase
from baseline ≥2 g/dL on three consecutive available visits during
the 24-week treatment period. The data from the primary endpoint
are as follows:
Primary Endpoint
Results
|
Regions
|
Overall
|
U.S., Canada and
Australia
and Western Europe*
|
Eastern
Europe
|
Treatment
Group
|
Fostamatinib
(n=45)
|
Placebo
(n=45)
|
Fostamatinib
(n=25)
|
Placebo
(n=28)
|
Fostamatinib
(n=20)
|
Placebo
(n=17)
|
Durable
hemoglobin
response rate n (%)
|
16 (35.6%)
|
12 (26.7%)
|
9 (36.0%)
|
3 (10.7%)
|
7 (35.0%)
|
9 (52.9%)
|
P-Value
|
P=0.398
|
P=0.03
|
P=0.304
|
*Post-hoc
analysis
|
The trial also included key secondary endpoints, including
hemoglobin response on at least one visit, change in Hgb from
baseline of ≥2 g/dL, use of permitted rescue therapy after week 4,
change in Hgb from baseline to end of treatment and change from
baseline to week 24 in Functional Assessment of Chronic Illness
Therapy – Fatigue (FACIT-F) scale. The data from the secondary
endpoints are as follows:
Secondary Endpoint
Results
|
|
Overall
|
U.S., Canada and
Australia
and Western Europe*
|
Eastern
Europe
|
Fostamatinib
(n=45)
|
Placebo
(n=45)
|
Fostamatinib
(n=25)
|
Placebo
(n=28)
|
Fostamatinib
(n=20)
|
Placebo
(n=17)
|
Number of subjects
with
hemoglobin response
on at least one
visit
n
(%)
|
21 (46.7%)
|
16 (35.6%)
|
13 (52.0%)
|
5 (17.9%)
|
8 (40.0%)
|
11 (64.7%)
|
Number of subjects
with
change in Hgb from
baseline of ≥2 g/dL
n
(%)
|
22 (48.9%)
|
16 (35.6%)
|
14 (56.0%)
|
5 (17.9%)
|
8 (40.0%)
|
11 (64.7%)
|
Change in mean
Hgb
from baseline to end of
treatment
LS Mean
(95% CI)
|
1.8
(1.06, 2.54)
|
1.85
(1.07, 2.63)
|
2.25
(1.19, 3.31)
|
1.27
(0.12, 2.41)
|
1.28
(-0.07,
2.64)
|
2.27
(0.88, 3.66)
|
Number of subjects
free
(no use) of rescue
therapy after Week 4
n (%)
|
18 (40.0%)
|
18 (40.0%)
|
12 (48.0%)
|
8 (28.6%)
|
6 (30.0%)
|
10 (58.8%)
|
Change from baseline
to Week 24 in Functional
Assessment of Chronic
Illness Therapy – Fatigue
(FACIT-F) scale
LS Mean
(95% CI)
|
2.9
(-0.70,
6.50)
|
1.9
(-1.85,
5.69)
|
7.0
(2.05,
11.88)
|
0.7
(-4.25,
5.74)
|
-0.7
(-6.28,
4.86)
|
4.7
(-1.33,
10.73)
|
*Post-hoc
analysis
|
Safety Results:
Across the trial's overall patient
population, fostamatinib was generally well-tolerated. The
safety profile of the product was consistent with prior clinical
experience and no new safety issues were discovered. The most
common adverse events (≥10%) with fostamatinib and placebo were
diarrhea (26.7% and 6.7%), hypertension (24.4% and 17.8%), fatigue
(15.6% and 11.1%), pyrexia (13.3% and 6.7%), nausea (13.3% and
8.9%), and dyspnea (13.3% and 11.1%). There were five deaths on the
study (2 with fostamatinib and 3 with placebo), all of which were
determined to be unrelated to study drug. The safety results
were consistent with the overall safety profile data collected to
date, which includes more than 3,900 patients across multiple
diseases. Safety results are as follows:
Safety
Results
|
|
Overall
|
U.S., Canada and
Australia,
and Western Europe*
|
Eastern
Europe
|
Fostamatinib
(n=45)
|
Placebo
(n=45)
|
Fostamatinib
(n=25)
|
Placebo
(n=28)
|
Fostamatinib
(n=20)
|
Placebo
(n=17)
|
Patients with at
least 1
Adverse Event (AE) n (%)
|
42 (93.3%)
|
40 (88.9%)
|
25
(100.0%)
|
28
(100.0%)
|
17 (85.0%)
|
12 (70.6%)
|
Patients with at
least 1
Serious Adverse Event (SAE)
n (%)
|
15 (33.3%)
|
17 (37.8%)
|
8 (32.0%)
|
13 (46.4%)
|
7 (35.0%)
|
4 (23.5%)
|
Patients with
Treatment-
related SAEs n (%)
|
3 (6.7%)
|
2 (4.4%)
|
2 (8.0%)
|
1 (3.6%)
|
1 (5.0%)
|
1 (5.8%)
|
Patients with an AE
≥ grade 3 n (%)
|
24 (53.3%)
|
19 (42.2%)
|
15 (60.0%)
|
16 (57.1%)
|
9 (45.0%)
|
3 (17.6%)
|
Patients with at
least one
Treatment-related AE n (%)
|
24 (53.3%)
|
12 (26.7%)
|
16 (64.0%)
|
10 (35.7%)
|
8 (40.0%)
|
2 (11.7%)
|
Patients who
discontinued
from study due to AEs n (%)
|
4 (8.9%)
|
6 (13.3%)
|
2 (8.0%)
|
5 (17.9%)
|
2 (10.0%)
|
1 (5.8%)
|
*Post-hoc
analysis
|
"While we are disappointed in the overall results, which were
impacted by a large placebo response rate from Eastern European
clinical sites, we are encouraged by the top-line results from the
U.S., Canada, Australia, and Western Europe. We continue to believe
fostamatinib has the potential to benefit patients with wAIHA, a
population with a serious unmet medical need," said Raul Rodriguez, President and Chief Executive
Officer of Rigel Pharmaceuticals. "We will continue to analyze the
data and look forward to discussing our findings with the FDA. On
behalf of the entire Rigel team, we are grateful to the patients,
their caregivers, and the healthcare professionals who participated
in the trial."
"There are currently no approved therapies specifically
indicated for wAIHA and the treatments that are currently used have
shortcomings related to efficacy, safety, and quality of life,"
said David Kuter, M.D., D.Phil.,
Director of Clinical Hematology at Massachusetts General Hospital,
Professor of Medicine at Harvard Medical
School, and Lead Investigator. "On balance, the findings
from the U.S., Canadian, Australian, and Western European trial
sites are supportive of fostamatinib for the treatment of wAIHA,
however, the confounding results from the Eastern European trial
sites require further analysis of the data from this trial. I look
forward to working with Rigel to better understand these data."
Of the 90 patients that completed the FORWARD Phase 3 study, 71
(79%) enrolled in the open-label extension study. Data from this
study will be reported later.
Conference Call and Webcast Today at 8:00 a.m. Eastern Time
Rigel will hold a
live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time).
Participants can access the live conference call by dialing
(877) 407-3088 (domestic) or (201) 389-0927 (international).
The conference call will also be webcast live and can be accessed
from the Investor Relations section of the company's website at
www.rigel.com. The webcast will be archived and available for
replay after the call via the Rigel website.
About AIHA
Autoimmune hemolytic anemia (AIHA) is a
rare, serious blood disorder in which the immune system produces
antibodies that lead to the destruction of the body's own red blood
cells. Warm antibody AIHA (wAIHA), which is the most common form of
AIHA, is characterized by the presence of antibodies that react
with the red blood cell surface at body temperature. wAIHA affects
approximately 36,000 adult patients in the
U.S.1 and can be a severe, debilitating disease. To
date, there are no disease-targeted therapies approved for wAIHA,
despite the unmet medical need that exists for these patients.
About the FORWARD Phase 3 Study
Fostamatinib is
currently being evaluated in a Phase 3 randomized, double-blind,
placebo-controlled clinical study in 90 patients with wAIHA who
have failed at least one prior treatment. The study will evaluate
the efficacy of fostamatinib versus placebo in achieving a durable
hemoglobin response, defined as a hemoglobin level ≥ 10 g/dL, with
an increase from baseline level of ≥ 2 g/dL, with the response not
being attributed to rescue therapy, and durability measure in
hemoglobin on three consecutive available visits during the 24-week
treatment period. Secondary endpoints include other measures of
hemoglobin response, use of rescue medication, and safety.
The FDA has granted fostamatinib Orphan Drug and Fast Track
designations for the treatment of patients with wAIHA.
Fostamatinib, commercially available in the U.S. under the brand
name TAVALISSE® (fostamatinib disodium hexahydrate)
tablets, is the first and only FDA-approved SYK inhibitor indicated
for the treatment of thrombocytopenia in adult patients with
chronic ITP who have had an insufficient response to a previous
treatment.
About Rigel
Rigel Pharmaceuticals, Inc., is a
biotechnology company dedicated to discovering, developing and
providing novel small molecule drugs that significantly
improve the lives of patients with hematologic disorders, cancer
and rare immune diseases. Rigel's pioneering research focuses on
signaling pathways that are critical to disease mechanisms. The
company's first FDA approved product is
TAVALISSE® (fostamatinib disodium hexahydrate)
tablets, the only oral spleen tyrosine kinase (SYK) inhibitor for
the treatment of adult patients with chronic immune
thrombocytopenia who have had an insufficient response to a
previous treatment. The product is also commercially available in
Europe, the United Kingdom (TAVLESSE) and Canada (TAVALISSE) for the treatment of
chronic immune thrombocytopenia in adult patients.
Fostamatinib is currently being studied in a Phase 3 clinical
trial (NCT03764618) for the treatment of warm autoimmune
hemolytic anemia (wAIHA)2; a Phase 3 clinical
trial (NCT04629703) for the treatment of
hospitalized high-risk patients
with COVID-192; and an NIH/NHLBI-sponsored Phase 3
clinical trial (ACTIV-4 Host Tissue Trial, NCT04924660) for
the treatment of COVID-19 in hospitalized patients.
Rigel's other clinical programs include its interleukin
receptor-associated kinase (IRAK) inhibitor program, and a
receptor-interacting serine/threonine-protein kinase (RIPK)
inhibitor program in clinical development with partner Eli Lilly
and Company. In addition, Rigel has product candidates in
development with partners BerGenBio ASA and Daiichi
Sankyo.
For further information, visit www.rigel.com or follow
us on Twitter or LinkedIn.
1. Prevalence: A. Zanella, et
al, haematologica 2014; 99(10); % Warm AIHA: T.
Kalfa; Hematology Am Soc Hematol Educ Program. 2016 Dec 2; 2016(1): 690–697
2. The product for this use or indication is investigational and
has not been proven safe or effective by any regulatory
authority.
Forward Looking Statements
This release contains
forward-looking statements relating to, among other things, the
topline data from the FORWARD trial in patients with wAIHA and our
expectations related to the potential and market opportunity for
fostamatinib as therapeutic for, among other things, wAIHA. Any
statements contained in this press release that are not statements
of historical fact may be deemed to be forward-looking statements.
Words such as "potential", "may", "expects", and similar
expressions are intended to identify these forward-looking
statements. These forward-looking statements are based on Rigel's
current expectations and inherently involve significant risks and
uncertainties. 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, risks that the FDA, EMA or other
regulatory authorities may make adverse decisions regarding
fostamatinib; risks that clinical trials may not be predictive of
real-world results or of results in subsequent clinical trials;
risks that fostamatinib may have unintended side effects, adverse
reactions or incidents of misuses; the availability of resources to
develop Rigel's product candidates; market competition; as well as
other risks detailed from time to time in Rigel's reports filed
with the Securities and Exchange Commission, including its
Quarterly Report on Form 10-Q for the period ended March 31, 2022 and subsequent filings. Rigel does
not undertake any obligation to update forward-looking statements
and expressly disclaims any obligation or undertaking to release
publicly any updates or revisions to any forward-looking statements
contained herein, except as required by law.
Contact for Investors & Media:
Jodi Sievers - Rigel
Pharmaceuticals
Phone: 650.624.1232
Email: ir@rigel.com
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