TG Therapeutics Announces Results from the ULTIMATE I & II Phase 3 Trials of Investigational Ublituximab in RMS Published in The New England Journal of Medicine
August 25 2022 - 7:30AM
TG Therapeutics, Inc. (NASDAQ: TGTX), today announced results
from the ULTIMATE I & II Phase 3 trials evaluating ublituximab,
the Company’s investigational anti-CD20 monoclonal antibody, in
patients with relapsing forms of multiple sclerosis (RMS), were
published in The New England Journal of Medicine (NEJM). Michael S.
Weiss, Chairman and Chief Executive Officer of TG Therapeutics
stated, “We are extremely pleased that the results from the
ULTIMATE I & II trials have been published in The New England
Journal of Medicine. We believe ublituximab’s novel mechanism of
action, coupled with the convenience of a one-hour infusion
represents a potential advance for patients with RMS and we are
pleased that this publication will share the ULTIMATE I and II data
with a broad audience. We continue to be singularly focused on
working toward the potential approval of ublituximab by the
December 28, 2022 PDUFA goal date, and if successful, being
prepared to launch early next year. We once again want to thank the
patients that participated in ULTIMATE I and II and the healthcare
providers at the sites that worked so hard on these trials.”
Lawrence Steinman, MD, Zimmermann Professor of Neurology &
Neurological Sciences, and Pediatrics at Stanford University and
Global Study Chair for the ULTIMATE I & II trials stated, “The
ULTIMATE trials found ublituximab treatment, compared to
teriflunomide, produced significantly lower annualized relapse
rates, reduction in the total number of MRI-detectable lesions, as
well as improved rates of patients achieving no evidence of disease
activity (NEDA). If approved, the unique attributes of ublituximab,
particularly its ability to be infused in a one-hour infusion every
six months following the first dose, may offer benefits to patients
with relapsing forms of multiple sclerosis.” Key Data from
the ULTIMATE I & II Trials
Primary Endpoint: Annualized Relapse Rate (ARR) Results
- In ULTIMATE I, treatment with
ublituximab resulted in an ARR of 0.08 (n=271), compared to 0.19
for teriflunomide (n=274), (p<0.001).
- In ULTIMATE II, treatment with
ublituximab resulted in an ARR of 0.09 (n=272), compared to 0.18
for teriflunomide (n=272), (p=0.002).
MRI Results
- In the ULTIMATE I trial, the mean
total number of gadolinium enhancing lesions per T1-weighted MRI
scan was 0.02 in the ublituximab group and 0.49 in the
teriflunomide group (rate ratio, 0.03; 95% CI, 0.02 to 0.06;
P<0.001); in the ULTIMATE II trial, the corresponding numbers
were 0.01 and 0.25 (rate ratio, 0.04; 95% CI, 0.02 to 0.06;
P<0.001).
- In the ULTIMATE I trial, the mean
total number of new or enlarging hyperintense lesions per
T2-weighted MRI scan was 0.21 in the ublituximab group and 2.79 in
the teriflunomide group (rate ratio, 0.08; 95% CI, 0.06 to 0.10;
P<0.001); in the ULTIMATE II trial, the corresponding numbers
were 0.28 and 2.83 (rate ratio, 0.10; 95% CI, 0.07 to 0.14;
P<0.001).
No Evidence of Disease Activity (NEDA) Results
- In ULTIMATE I, NEDA was
observed in 44.6% of ublituximab treated patients and in
15% of the teriflunomide treated patients. In ULTIMATE
II, NEDA was observed in
43% of ublituximab treated patients and in 11.4% of
teriflunomide treated patients.
Prespecified Pooled Disability Results
- In the prespecified pooled analysis,
5.2% of the participants in the ublituximab group had worsening of
disability confirmed at 12 weeks, as compared with 5.9% of the
participants in the teriflunomide group (hazard ratio, 0.84; 95%
CI, 0.50 to 1.41; P = 0.51); 3.3% of the participants in the
ublituximab group had worsening of disability confirmed at 24
weeks, as compared with 4.8% of the participants in the
teriflunomide group (hazard ratio, 0.66; 95% CI, 0.36 to 1.21).
These results were not considered to be significantly different
between treatment groups.
- In the prespecified pooled tertiary
analysis that was not included in the hierarchical analysis and
from which no conclusions can be drawn, 12.0% of the participants
who received ublituximab had lessening of disability confirmed at
12 weeks, as compared with 6.0% of the participants who received
teriflunomide (hazard ratio, 2.16; 95% CI, 1.41 to 3.31); 9.6% of
the participants who received ublituximab had lessening of
disability confirmed at 24 weeks, as compared with 5.1% of the
participants who received teriflunomide (hazard ratio, 2.03; 95%
CI, 1.27 to 3.25).
Safety/Tolerability
- In a pooled analysis of the two
trials, 486 of 545 participants (89.2%) who received ublituximab
and 501 of 548 participants (91.4%) who received teriflunomide had
at least one adverse event. Grade 3 or higher adverse events
occurred in 116 participants (21.3%) who received ublituximab and
in 77 (14.1%) who received teriflunomide.
- The most common adverse event
associated with ublituximab was infusion related reactions (47.7%
of patients who received ublituximab experienced at least one
infusion-related reaction vs. 12.2% for the teriflunomide
group).
Based primarily on the results of the ULTIMATE I & II
trials, marketing applications for ublituximab to treat patients
with RMS have been accepted and are currently under review by the
US Food and Drug Administration (FDA) and the European Medicines
Agency (EMA). As previously announced, ublituximab was granted a
Prescription Drug Fee User Act (PDUFA) goal date of December 28,
2022 by the FDA.
ABOUT THE ULTIMATE I & II PHASE 3
TRIALSULTIMATE I and ULTIMATE II are two independent Phase
3, randomized, double-blinded, active-controlled, global,
multi-center studies evaluating the efficacy and
safety/tolerability of ublituximab (450mg dose administered by
one-hour intravenous infusion every 6 months, following a Day 1
infusion of 150mg over four hours and a Day 15 infusion of 450mg
over one hour) versus teriflunomide (14mg oral tablets taken once
daily) in subjects with relapsing forms of Multiple Sclerosis
(RMS). The ULTIMATE I & II trials enrolled a total of 1,094
patients with RMS across 10 countries. These trials were led by
Lawrence Steinman, MD, Zimmermann Professor of Neurology &
Neurological Sciences, and Pediatrics at Stanford University and
were conducted under a Special Protocol Assessment (SPA) agreement
with the U.S. Food and Drug Administration (FDA). As previously
announced, both studies met their primary endpoint with ublituximab
treatment demonstrating a statistically significant reduction in
annualized relapse rate (ARR) compared to teriflunomide over a
96-week period (p<0.005 in each trial). Additional information
on these clinical trials can be found at www.clinicaltrials.gov
(NCT03277261; NCT03277248).
ABOUT UBLITUXIMAB Ublituximab is an
investigational glycoengineered monoclonal antibody that targets a
unique epitope on CD20-expressing B-cells. When ublituximab binds
to the B-cell it triggers a series of immunological reactions,
including antibody-dependent cellular cytotoxicity (ADCC) and
complement dependent cytotoxicity (CDC), leading to destruction of
the cell. Additionally, ublituximab is uniquely designed to lack
certain sugar molecules normally expressed on the antibody. Removal
of these sugar molecules, a process called glycoengineering, has
been shown to enhance the potency of ublituximab, especially the
ADCC activity. Targeting CD20 using monoclonal antibodies has
proven to be an important therapeutic approach for the management
of B-cell malignancies and autoimmune disorders, both diseases
driven by the abnormal growth or function of B-cells.ABOUT
MULTIPLE SCLEROSIS Relapsing multiple sclerosis (RMS) is a
chronic demyelinating disease of the central nervous system (CNS)
and includes people with relapsing-remitting multiple sclerosis
(RRMS) and people with secondary progressive multiple sclerosis
(SPMS) who continue to experience relapses. RRMS is the most common
form of multiple sclerosis (MS) and is characterized by episodes of
new or worsening signs or symptoms (relapses) followed by periods
of recovery. It is estimated that nearly 1 million people are
living with MS in the United States and approximately 85% are
initially diagnosed with RRMS.1,2 The majority of people who
are diagnosed with RRMS will eventually transition to SPMS, in
which they experience steadily worsening disability over time.
Worldwide, more than 2.3 million people have a diagnosis of
MS.1
ABOUT TG THERAPEUTICSTG Therapeutics is a
biopharmaceutical company focused on the acquisition, development
and commercialization of novel treatments for B-cell diseases. In
addition to a research pipeline including several investigational
medicines, TG has completed a Phase 3 program for ublituximab, an
investigational glycoengineered monoclonal antibody that targets a
unique epitope on CD20-expressing B-cells, to treat patients with
relapsing forms of multiple sclerosis (RMS). For more information,
visit www.tgtherapeutics.com, and follow us on
Twitter @TGTherapeutics and Linkedin.Cautionary
StatementThis press release contains forward-looking
statements that involve a number of risks and uncertainties. For
those statements, we claim the protection of the safe harbor for
forward-looking statements contained in the Private Securities
Litigation Reform Act of 1995. Such forward-looking statements
include but are not limited to statements regarding the FDA review
of the Biologics License Application (BLA) for ublituximab for the
treatment of relapsing forms of Multiple Sclerosis (RMS) and the
commercial potential of ublituximab for the treatment of RMS if the
BLA is approved.
Any forward-looking statements in this press release are based
on management's current expectations and beliefs and are subject to
a number of risks, uncertainties and important factors that may
cause actual events or results to differ materially from those
expressed or implied by any forward-looking statements contained in
this press release. In addition to the risk factors identified from
time to time in our reports filed with the U.S. Securities and
Exchange Commission (SEC), factors that could cause our actual
results to differ materially include the following: the risk that
the clinical results from the ULTIMATE I & II trials will not
support regulatory approval of ublituximab to treat RMS for
efficacy, safety or other issues or, if approved, that we will not
receive regulatory approval within the timeline projected; the risk
that ublituximab will not be commercially successful, if approved;
the risk that the data from the ULTIMATE I & II trials that we
announce or publish may change, or the perceived product profile
may be impacted, as more data are analyzed; the risk that data may
emerge from future clinical studies or from adverse event reporting
that may affect the perceived safety and tolerability profile and
commercial potential of ublituximab; our ability to expand our
commercial infrastructure, and successfully launch, market and sell
ublituximab in RMS, if approved; the Company’s reliance on third
parties for manufacturing, distribution and supply, and a range of
other support functions for our commercial and clinical products,
including ublituximab; the uncertainties inherent in research and
development; and the risk that the ongoing COVID-19 pandemic and
associated government control measures have an adverse impact on
our research and development plans or commercialization efforts.
Further discussion about these and other risks and uncertainties
can be found in our Annual Report on Form 10-K for the fiscal year
ended December 31, 2021, our most recent Quarterly Report
filed on Form 10-Q, and our other filings with the U.S.
Securities and Exchange Commission. Any forward-looking
statements set forth in this press release speak only as of the
date of this press release. We do not undertake to update any of
these forward-looking statements to reflect events or circumstances
that occur after the date hereof. This press release and prior
releases are available at www.tgtherapeutics.com. The information
found on our website is not incorporated by reference into this
press release and is included for reference purposes only.
CONTACT:
Investor Relations Email:
ir@tgtxinc.comTelephone: 1.877.575.TGTX (8489), Option 4
Media Relations: Email:
media@tgtxinc.comTelephone: 1.877.575.TGTX (8489), Option 6
_________________________________________________________
1. MS Prevalence. National Multiple
Sclerosis Society
website. https://www.nationalmssociety.org/About-the-Society/MS-Prevalence.
Accessed October 26, 2020. 2. Multiple
Sclerosis International Federation, 2013 via Datamonitor p.
236.
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