TG Therapeutics, Inc. (NASDAQ: TGTX), today announced that the
U.S. Food and Drug Administration (FDA) has accepted the
Biologics License Application (BLA) for ublituximab, the Company’s
investigational glycoengineered anti-CD20 monoclonal antibody, in
combination with UKONIQ® (umbralisib), the Company’s
once-daily, oral, inhibitor of PI3K-delta and CK1-epsilon, as a
treatment for patients with chronic lymphocytic leukemia (CLL) and
small lymphocytic lymphoma (SLL). The FDA has set a Prescription
Drug User Fee Act (PDUFA) goal date of March 25, 2022. The FDA also
notified the Company that it is not currently planning to hold an
advisory committee meeting to discuss this application.
Michael S. Weiss, Executive Chairman and Chief Executive Officer
of TG Therapeutics stated, “We are extremely pleased that the
ublituximab BLA has been accepted by the FDA. This is an important
milestone for us as it brings us one step closer to our goal of
providing a novel combination treatment option to patients with
both treatment naive and relapsed or refractory CLL and SLL. We
look forward to collaborating with the FDA throughout this review
process.”
The BLA submission was based on the results of the UNITY-CLL
trial, a global Phase 3 trial evaluating the combination of
ublituximab plus UKONIQ (U2) compared to obinutuzumab plus
chlorambucil in patients with treatment naive and relapsed or
refractory CLL. The U.S. FDA previously granted Fast
Track designation to the combination of ublituximab and UKONIQ for
the treatment of adult patients with CLL and orphan drug
designation for ublituximab in combination with UKONIQ for the
treatment of CLL.
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. 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, 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 three 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 registered 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
UKONIQ® (umbralisib), the FDA review and potential approval of the
BLA and the timing thereof, the potential benefits, safety and
efficacy of ublituximab in combination with UKONIQ in CLL, 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: 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, as updated by our subsequent Quarterly Reports on Form
10-Q, 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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