TG Therapeutics, Inc. (NASDAQ: TGTX) today announced the
publication of results from an integrated safety analysis of
UKONIQ® (umbralisib), the Company’s inhibitor of PI3k-delta
and CK1-epsilon, in patients with relapsed or refractory lymphoid
malignancies in Blood Advances, a journal of the American
Society of Hematology. Michael S. Weiss, the Company’s Chairman and
Chief Executive Officer stated, “We are pleased that the integrated
safety analysis of 371 patients treated with UKONIQ has been
published in Blood Advances. We believe these data further support
the differentiated safety profile of UKONIQ, the first and only
PI3k-delta and CK1-epsilon inhibitor, which is now commercially
available to patients with relapsed or refractory marginal zone
lymphoma and follicular lymphoma. As we strive toward obtaining FDA
approval of the investigational combination of UKONIQ and
ublituximab, U2, in CLL by the PDUFA goal date of March 25, 2022,
furthering our understanding of the safety and tolerability profile
of UKONIQ remains paramount to us.”Matthew S. Davids, MD, MMSc,
lead author of the integrated safety study and Director of Clinical
Research in the Division of Lymphoma at Dana-Farber Cancer
Institute stated, “Historically, the use of PI3K-delta inhibitors
has been limited by high discontinuation rates. The integrated
safety data analysis of umbralisib published [today/yesterday] is
encouraging for patients, especially given the low rate of
discontinuations due to adverse events observed. Our analysis
further underscores the potential role of umbralisib in the
treatment of relapsed or refractory marginal zone and follicular
lymphoma and may support the future utilization of umbralisib in
combination therapies for patients with lymphoid malignancies.”The
manuscript includes integrated comprehensive toxicity data from 4
open-label phase 1 and 2 studies that included 371 adult patients
with relapsed or refractory non-Hodgkin lymphoma (NHL), including
patients with follicular lymphoma (n=147), marginal zone lymphoma
(n=81), diffuse large B-cell lymphoma/mantle cell lymphoma (n=74),
chronic lymphocytic leukemia (n=43) and other (n=25). All patients
were treated with umbralisib at 800mg or higher once daily. At data
cutoff, median duration of umbralisib treatment was 5.9 months
(range, 0.1-75.1), and 107 patients (28.8%) received umbralisib for
≥12 months.
Key highlights from this manuscript include:
- The most common grade ≥3
treatment-emergent adverse events (TEAEs) were neutropenia (11.3%),
diarrhea (7.3%), and increase aminotransferases (5.7%).
- AEs of special interest were limited
and included pneumonia in 29 patients (7.8%), noninfectious colitis
in 9 patients (2.4%), and pneumonitis in 4 patients (1.1%).
- Treatment-emergent serious AEs
occurred in 95/371 patients (25.6%).
- AEs led to discontinuation of
umbralisib in 51 patients (13.7%).
- No cumulative toxicity over time was
observed.
These data are described further in the manuscript entitled,
“Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε
inhibitor, in relapsed/refractory lymphoid malignancies,” which was
published online in Blood Advances. The online version of the
article can be accessed at
https://pubmed.ncbi.nlm.nih.gov/34547767/. 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
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.IMPORTANT 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. 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 UKONIQ® (umbralisib) for the treatment of
relapsed or refractory (R/R) marginal zone lymphoma (MZL) and
follicular lymphoma (FL); the safety and tolerability profile of
UKONIQ; and ongoing research of combination regimens that include
UKONIQ. In addition to the risk factors identified from time to
time in our reports filed with the Securities and Exchange
Commission, factors that could cause our actual results to differ
materially include the following: the risk that as UKONIQ or any
future approved products are used more widely or for a longer
duration after being brought to market, data may emerge from
clinical studies, including confirmatory or other post-marketing
studies, or from adverse event reporting that may affect the
perceived safety and tolerability profile and commercial potential
of our products; the Company’s ability to maintain a commercial
infrastructure and to successfully market and sell UKONIQ or future
products, if approved; approval of expanded or additional
indications for UKONIQ and for our product candidates, including
ublituximab, in the U.S.or to our ability to obtain marketing
approval for any of our products in additional geographies, outside
of the U.S.; 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
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