TG Therapeutics, Inc. (NASDAQ: TGTX), today announced the
initiation of patient enrollment into the ULTRA-V Phase 3
randomized trial, evaluating the time-limited triple combination of
UKONIQ™ (umbralisib), the Company’s once-daily, inhibitor of
PI3K-delta and CK1-epsilon, ublituximab, the Company’s
investigational glycoengineered anti-CD20 monoclonal antibody, and
venetoclax, compared to the continuous doublet combination of
UKONIQ plus ublituximab (U2) in patients with both frontline and
relapsed or refractory chronic lymphocytic leukemia (CLL). The
primary endpoint for the ULTRA-V Phase 3 trial is Progression-free
Survival (PFS), and the trial is designed support the full approval
of the triple combination of U2 plus venetoclax.
The Company also announced completion of enrollment into the
ULTRA-V Phase 2 global, single arm trial evaluating the triple
combination of U2 plus venetoclax. This primary endpoint for this
trial is overall response rate (ORR) and complete response (CR)
rate, and the trial completed enrollment with approximately 165
patients enrolled. The trial enrolled patients with front line CLL,
as well as relapsed or refractory CLL, including patients who were
refractory to prior Bruton’s Kinase Inhibitor (BTK) therapy.
Richard R. Furman, MD, Director of CLL Research Center at Weill
Cornell Medicine and Study Chair for the ULTRA-V Phase 2 and Phase
3 trials stated, “We are excited to launch this pivotal Phase 3
study based on the promising Phase 1 clinical results reported to
date on the triplet combination of UKONIQ, ublituximab and
venetoclax in patients with CLL. While recent approvals provide
excellent treatment options for patients, disease progression and
treatment tolerability still remain problematic for many
patients. Our belief is that time-limited treatment regimens,
such as U2 plus venetoclax, have the potential to produce
meaningful responses without the need to expose patients to
continuous therapy and related toxicities. We look forward to
presenting the results of the Phase 2 portion of this study at a
future medical meeting. I want to thank my colleagues for their
strong support of the Phase 2 ULTRA-V trial and look forward to
continuing and expanding our efforts now in Phase 3.”
Michael S. Weiss, Executive Chairman and Chief Executive Officer
of TG Therapeutics stated, “We are extremely pleased with the rapid
enrollment seen in the ULTRA-V Phase 2 trial, with approximately
165 patients enrolled in approximately 16 months throughout a
limited number of U.S. trial sites, with the majority of the
enrollment taking place in 2020 during the height of the COVID-19
pandemic. We are further encouraged by the strong interest of new
trial sites to participate in the Phase 3 portion of the trial. We
believe the encouraging early results observed in the Phase 1 trial
of U2 plus venetoclax, led by Dr. Paul Barr at the University of
Rochester, which were most recently presented at the ASH annual
meeting in 2020, are supportive of our decision to quickly initiate
the ULTRA-V Phase 2 and 3 trials. We look forward to providing an
update from the Phase 1 trial later this year and initial results
from the Phase 2 portion of the ULTRA-V trial in
2022.”ABOUT ULTRA-V PHASE 3 TRIAL The ULTRA-V
Phase 3 trial is an open-label, multicenter, randomized controlled
clinical trial comparing the time-limited triple combination of
UKONIQ and ublituximab (U2) plus venetoclax, to an active control
arm of continuous U2. The Phase 3 trial includes two independent
randomized cohorts of CLL subjects: a treatment-naïve cohort and a
previously treated cohort, with each cohort being enrolled and
evaluated independently of each other. The primary endpoint for the
trial is Progression-free Survival (PFS). This trial is being led
by Richard R. Furman, MD, Director of CLL Research Center at Weill
Cornell Medicine and targeting over 60 U.S. trial
sites.ABOUT ULTRA-V PHASE 2 TRIAL The ULTRA-V
Phase 2 trial, (NCT03801525), is an open-label, multicenter, trial
designed to investigate the efficacy and safety of ublituximab and
UKONIQ combined with venetoclax in subjects with CLL. The primary
endpoint of the trial is overall response rate (ORR) and Complete
Response (CR) rate. The trial enrolled approximately 165 patients
with front line and previously treated CLL at 26 sites throughout
the United States.
ABOUT U2 PLUS VENETOCLAX PHASE 1 TRIAL The
Phase 1/2 trial, (NCT03379051), is a multi-center, dose-escalation
trial designed to assess the safety and efficacy of U2 plus
venetoclax in patients with relapsed or refractory CLL. The primary
objective of the trial is to evaluate the safety of venetoclax
after U2 induction. The secondary objectives are clinical efficacy
as defined by ORR (including CR rate), PFS, and undetectable
minimal residual disease (MRD) rate after 12 cycles of therapy. The
trial enrolled approximately 50 CLL patients, and interim results
were most recently presented on 43 CLL patients at the American
Society of Hematology (ASH) annual meeting in December 2020.
ABOUT CHRONIC LYMPHOCYTIC LEUKEMIAChronic
lymphocytic leukemia (CLL) is the most common type of adult
leukemia. It is estimated there will be more than 20,000 new cases
of CLL diagnosed in the United States in 2020 and approximately
45,000 new cases globally in 2020.1,2 Although signs and
symptoms of CLL may disappear for a period of time after initial
treatment, the disease is considered incurable and many people will
require additional treatment due to the return of malignant
cells.
ABOUT TG THERAPEUTICS, INC. TG
Therapeutics is a fully-integrated, commercial stage
biopharmaceutical company focused on the acquisition, development
and commercialization of novel treatments for B-cell malignancies
and autoimmune diseases. In addition to an active research pipeline
including five investigational medicines across these therapeutic
areas, TG has received accelerated approval from
the U.S. FDA for UKONIQ™ (umbralisib), for the
treatment of adult patients with relapsed/refractory marginal zone
lymphoma who have received at least one prior anti-CD20-based
regimen and relapsed/refractory follicular lymphoma who have
received at least three prior lines of systemic therapies.
Currently, the Company has two programs in Phase 3 development for
the treatment of patients with relapsing forms of multiple
sclerosis (RMS) and patients with chronic lymphocytic leukemia
(CLL) and several investigational medicines in Phase 1 clinical
development. For more information,
visit www.tgtherapeutics.com, and follow us on
Twitter @TGTherapeutics and Linkedin.UKONIQ™ is
a trademark of TG Therapeutics, Inc.
ABOUT
UKONIQ™ (umbralisib) UKONIQ is the
first and only oral inhibitor of phosphoinositide 3 kinase
(PI3K) delta and casein kinase 1 (CK1) epsilon.
PI3K-delta is known to play an important role in supporting
cell proliferation and survival, cell differentiation,
intercellular trafficking and immunity and is expressed in both
normal and malignant B-cells. CK1-epsilon is a regulator of
oncoprotein translation and has been implicated in the pathogenesis
of cancer cells, including lymphoid malignancies.
UKONIQ is indicated for the treatment of adult patients with
relapsed or refractory marginal zone lymphoma (MZL) who have
received at least one prior anti-CD20-based regimen and for the
treatment of adult patients with relapsed or refractory follicular
lymphoma (FL) who have received at least three prior lines of
systemic therapy.
These indications are approved under accelerated approval based
on overall response rate. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory trial.
IMPORANT SAFETY
INFORMATIONInfections: Serious, including
fatal, infections occurred in patients treated with UKONIQ. Grade 3
or higher infections occurred in 10% of 335 patients, with fatal
infections occurring in <1% . The most frequent Grade ≥3
infections included pneumonia, sepsis, and urinary tract infection.
Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and
consider prophylactic antivirals during treatment with UKONIQ to
prevent CMV infection, including CMV reactivation. Monitor for any
new or worsening signs and symptoms of infection, including
suspected PJP or CMV, during treatment with UKONIQ. For Grade 3 or
4 infection, withhold UKONIQ until infection has resolved. Resume
UKONIQ at the same or a reduced dose. Withhold UKONIQ in patients
with suspected PJP of any grade and permanently discontinue in
patients with confirmed PJP. For clinical CMV infection or viremia,
withhold UKONIQ until infection or viremia resolves. If UKONIQ is
resumed, administer the same or reduced dose and monitor patients
for CMV reactivation by PCR or antigen test at least
monthly.Neutropenia: Serious neutropenia occurred
in patients treated with UKONIQ. Grade 3 neutropenia developed in
9% of 335 patients and Grade 4 neutropenia developed in 9%. Monitor
neutrophil counts at least every 2 weeks for the first 2 months of
UKONIQ and at least weekly in patients with neutrophil count <1
x 109/L (Grade 3-4) neutropenia during treatment with UKONIQ.
Consider supportive care as appropriate. Withhold, reduce dose, or
discontinue UKONIQ depending on the severity and persistence of
neutropenia.Diarrhea or Non-Infectious Colitis:
Serious diarrhea or non-infectious colitis occurred in patients
treated with UKONIQ. Any grade diarrhea or colitis occurred in 53%
of 335 patients and Grade 3 occurred in 9%. For patients with
severe diarrhea (Grade 3, i.e., > 6 stools per day over
baseline) or abdominal pain, stool with mucus or blood, change in
bowel habits, or peritoneal signs, withhold UKONIQ until resolved
and provide supportive care with antidiarrheals or enteric acting
steroids as appropriate. Upon resolution, resume UKONIQ at a
reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis
of any grade, discontinue UKONIQ. Discontinue UKONIQ for
life-threatening diarrhea or
colitis.Hepatotoxicity: Serious hepatotoxicity
occurred in patients treated with UKONIQ. Grade 3 and 4
transaminase elevations (ALT and/or AST) occurred in 8% and <1%,
respectively, in 335 patients. Monitor hepatic function at baseline
and during treatment with UKONIQ. For ALT/AST greater than 5 to
less than 20 times ULN, withhold UKONIQ until return to less than 3
times ULN, then resume at a reduced dose. For ALT/AST elevation
greater than 20 times ULN, discontinue UKONIQ. Severe
Cutaneous Reactions: Severe cutaneous reactions, including
a fatal case of exfoliative dermatitis, occurred in patients
treated with UKONIQ. Grade 3 cutaneous reactions occurred in 2% of
335 patients and included exfoliative dermatitis, erythema, and
rash (primarily maculo-papular). Monitor patients for new or
worsening cutaneous reactions. Review all concomitant medications
and discontinue any potentially contributing medications. Withhold
UKONIQ for severe (Grade 3) cutaneous reactions until resolution.
Monitor at least weekly until resolved. Upon resolution, resume
UKONIQ at a reduced dose. Discontinue UKONIQ if severe cutaneous
reaction does not improve, worsens, or recurs. Discontinue UKONIQ
for life-threatening cutaneous reactions or SJS, TEN, or DRESS of
any grade. Provide supportive care as appropriate. Allergic
Reactions Due to Inactive Ingredient FD&C Yellow No.
5: UKONIQ contains FD&C Yellow No. 5 (tartrazine),
which may cause allergic-type reactions (including bronchial
asthma) in certain susceptible persons, frequently in patients who
also have aspirin hypersensitivity.Embryo-fetal
Toxicity: Based on findings in animals and its mechanism
of action, UKONIQ can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. Advise females and males with female partners of
reproductive potential to use effective contraception during
treatment and for at least one month after the last
dose.Serious adverse reactions occurred in 18% of
221 patients who received UKONIQ. Serious adverse reactions that
occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia
(3%), sepsis (2%), and urinary tract infection (2%). Permanent
discontinuation of UKONIQ due to an adverse reaction occurred in
14% of patients. Dose reductions of UKONIQ due to an adverse
reaction occurred in 11% of patients. Dosage interruptions of
UKONIQ due to an adverse reaction occurred in 43% of patients.
The most common adverse reactions
(>15%), including laboratory abnormalities, in 221 patients who
received UKONIQ were increased creatinine (79%), diarrhea-colitis
(58%, 2%), fatigue (41%), nausea (38%), neutropenia (33%), ALT
increase (33%), AST increase (32%), musculoskeletal pain (27%),
anemia (27%), thrombocytopenia (26%), upper respiratory tract
infection (21%), vomiting (21%), abdominal pain (19%), decreased
appetite (19%), and rash (18%).Lactation: Because
of the potential for serious adverse reactions from umbralisib in
the breastfed child, advise women not to breastfeed during
treatment with UKONIQ and for at least one month after the last
dose.Please visit
www.tgtherapeutics.com/prescribing-information/uspi-ukon for full
Prescribing Information and Medication Guide.
__________________________________________________
1 Cancer Stat Facts: Leukemia — Chronic Lymphocytic
Leukemia (CLL). National Cancer Institute Surveillance,
Epidemiology, and End Results Program
website. https://seer.cancer.gov/statfacts/html/clyl.html.
Accessed October 26, 2020.2 EpiCast Report: Chronic Lymphocytic
Leukemia – Epidemiology Forecast to 2025. Available
at: https://store.globaldata.com/report/gdhcer164-17–epicast-report-chronic-lymphocytic-leukemia-epidemiology-forecast-to-2025/.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 U.S. Private Securities
Litigation Reform Act of 1995. Such forward-looking statements
include but are not limited to statements regarding the
expectations and plans for the clinical trials evaluating
UKONIQ™ (umbralisib) and ublituximab (U2) in combination with
venetoclax, the availability of results from those trials, and the
potential of U2 in combination with venetoclax as a treatment for
CLL.
In addition to the risk factors identified from time to time in
our reports filed with the U.S. Securities and Exchange
Commission, factors that could cause our actual results to differ
materially are the following: the risk that we will not be able to
meet the clinical trial or regulatory submission timelines that we
project or achieve other anticipated milestones; the risk that
interim, top-line, or other early clinical trial results, that may
have influenced our decision to proceed with additional clinical
trials, including the clinical studies evaluating U2 in combination
with venetoclax, will not be reproduced in final data sets or in
future studies; the risk that the safety profile observed with
UKONIQ, ublituximab, or combinations thereof, may change as
additional patients are exposed for longer durations; the risk that
the combination of U2 with venetoclax will not prove to be a safe
and efficacious regimen; the risk that the ULTRA-V clinical trials,
if positive, will not support regulatory approval of U2 in
combination with venetoclax in the U.S. or additional geographies,
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, 2020 and in 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:
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