TG Therapeutics, Inc. (NASDAQ: TGTX), today announced the
completion of the rolling submission of a Biologics License
Application (BLA) to the U.S. Food and Drug
Administration (FDA) requesting approval of ublituximab, the
Company’s investigational glycoengineered anti-CD20 monoclonal
antibody, in combination with UKONIQTM (umbralisib) , the Company’s
once-daily, oral, inhibitor of PI3K-delta and CK1-epsilon, as a
treatment for patients with chronic lymphocytic leukemia (CLL).
The U.S. FDA previously granted Fast Track designation to the
combination of ublituximab and umbralisib (U2) for the treatment of
adult patients with CLL and orphan drug designation for
ublituximab in combination with umbralisib for the treatment of
CLL. The BLA submission was based on the results of the UNITY-CLL
trial, a global Phase 3 trial evaluating the combination of
umbralisib plus ublituximab (U2) compared to obinutuzumab plus
chlorambucil in patients with previously untreated and
relapsed/refractory chronic lymphocytic leukemia (CLL).
Michael S. Weiss, Executive Chairman and Chief Executive Officer
of TG Therapeutics stated, “The rapid completion of this BLA
submission is a critical step forward in our mission to bring our
first proprietary combination regimen to patients with both
treatment naïve and relapsed or refractory chronic lymphocytic
leukemia. The FDA has previously granted the U2 combination both
fast track designation as well as orphan drug designation for
patients with CLL and we look forward to continuing to work closely
with the FDA with the goal of bringing this novel treatment regimen
to patients as quickly as possible.” Mr. Weiss continued, “I want
to thank the patients, their families and caregivers, as well as
the research teams who participated in the UNITY-CLL trial, and
also commend the TG team for their hard work to get this submission
completed ahead of schedule.”ABOUT UNITY-CLL PHASE 3
TRIAL UNITY-CLL is a global Phase 3 randomized controlled
clinical trial comparing the combination of ublituximab plus UKONIQ
(umbralisib), or U2, to an active control arm of obinutuzumab plus
chlorambucil in patients with both treatment-naïve and relapsed or
refractory chronic lymphocytic leukemia (CLL). The trial randomized
patients into four treatment arms: ublituximab single agent, UKONIQ
single agent, ublituximab plus UKONIQ, and an active control arm of
obinutuzumab plus chlorambucil. A prespecified interim
analysis was conducted to assess the contribution of ublituximab
and UKONIQ in the U2 combination arm and allowed for the
termination of the single agent arms. Accordingly, the UNITY-CLL
Phase 3 trial continued enrollment in a 1:1 ratio into the two
combination arms: the investigational arm of U2 and the control arm
of obinutuzumab plus chlorambucil. Approximately 420 subjects
enrolled to the two combination arms and approximately 60% of
patients were treatment-naïve and 40% were relapsed or refractory.
The primary endpoint for this study was superior progression-free
survival (PFS) for the U2 combination compared to the control arm
to support the submission of the U2 combination in CLL. The trial
met its primary endpoint and results were presented at the American
Society of Hematology (ASH) Annual Meeting in December 2020. The
UNITY-CLL Phase 3 trial is being conducted under a Special Protocol
Assessment (SPA) agreement with the U.S. Food and Drug
Administration (FDA).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 FAST TRACKFast Track is a program
designed to expedite the development and review of drugs that treat
serious conditions and that demonstrate the potential to address an
unmet medical need. Filling an unmet medical need is defined as
providing a therapy where none exists or providing a therapy that
may be potentially better than available therapy. A drug that
receives Fast Track designation is eligible for more
frequent interactions with the FDA, priority review if relevant
criteria are met, and rolling submission of the Biologics License
Application or New Drug Application.ABOUT ORPHAN DRUG
DESIGNATIONOrphan drug designation is granted by
the FDA to drugs and biologics which are defined as those
intended for the safe and effective treatment, diagnosis or
prevention of rare diseases/disorders that affect fewer than
200,000 people in the U.S. Orphan drug designation
provides certain incentives which may include tax credits towards
the cost of clinical trials and prescription drug user fee waivers.
If a product that has orphan drug designation subsequently receives
the first FDA approval for the disease for which it has
such designation, the product is entitled to orphan product
exclusivity.
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, UKONIQTM (umbralisib) received accelerated approval
from the U.S. FDA 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 programs in Phase 3
development for the treatment of patients with relapsing forms of
multiple sclerosis (RMS) and for the treatment of patients
with chronic lymphocytic leukemia (CLL) as well as several
investigational medicines in Phase 1 clinical development. For
more information, visit www.tgtherapeutics.com, and follow us
on
Twitter @TGTherapeutics and Linkedin.UKONIQTM 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 within the meaning of the U.S. Private
Securities Litigation Reform Act of 1995, including statements
relating to the BLA submission of ublituximab in combination with
UKONIQTM (umbralisib), the clinical development of our product
candidates, and anticipated milestones. 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: risk
that the FDA will not accept the BLA submission of ublituximab in
combination with UKONIQ in patients with CLL, or if accepted, the
risk that the FDA will not approve the BLA submission; the risk
that fast track designation may not actually lead to a faster
regulatory review or approval process; the risk that safety issues
or trends will be observed in the UNITY-CLL study or in other
studies that prevent approval of ublituximab in combination with
UKONIQ; the risk that ublituximab in combination with UKONIQ, or
any other product candidates, will not be commercially successful
if approved; the risk that the differentiated tolerability profile
for UKONIQ previously observed in clinical trials will not be
reproduced in the UNITY-CLL trial or any other on-going studies;
our ability to successfully and cost effectively complete
preclinical and clinical trials; 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:
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
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