TG Therapeutics, Inc. (NASDAQ: TGTX) today announced the
publication of results from the UNITY-NHL Phase 2b trial evaluating
UKONIQ™ (umbralisib), the Company’s inhibitor of PI3k-delta and
CK1-epsilon, in patients with relapsed or refractory indolent
non-Hodgkin Lymphoma (NHL) in the Journal of Clinical Oncology
(JCO).
Michael S. Weiss, the Company’s Executive Chairman and Chief
Executive Officer stated, “We are extremely pleased that the
results of the UNITY-NHL trial which supported the recent approval
of umbralisib, now called UKONIQ, in relapsed or refractory
marginal zone and follicular lymphoma, have been published in the
prestigious Journal of Clinical Oncology. The data published
yesterday, and previously presented at the ASH 2020 conference,
highlight the utility of UKONIQ across these diseases. As the first
and only inhibitor of both PI3K-delta and CK1-epsilon, which is now
commercially available, we believe UKONIQ offers an important new
treatment option for patients.”
Pier Luigi Zinzani, MD, PhD, Professor, Institute of Hematology,
“L. e A. Seràgnoli”, University of Bologna, and Global Chair of the
UNITY-NHL Phase 2b study stated, “The data published yesterday as
well as the recent U.S. FDA approval of umbralisib in relapsed or
refractory marginal zone lymphoma and follicular lymphoma, are
encouraging for patients suffering from these diseases, especially
given the lack of a standard of care in these settings. As we see
from the UNITY-NHL publication, umbralisib offers meaningful
clinical activity across both marginal zone and follicular lymphoma
and a manageable safety profile with relatively low rates of immune
mediated toxicities and discontinuations due to adverse events.”
The manuscript includes data from 208 patients with relapsed or
refractory iNHL, including 69 marginal zone lymphoma (MZL), 117
follicular lymphoma (FL), and 22 small lymphocytic lymphoma (SLL)
patients who were unresponsive to prior treatments (≥1 MZL; ≥2
FL/SLL), including anti-CD20–based therapy. Patients were
administered umbralisib 800 mg orally once-daily until disease
progression, unacceptable toxicity, or study withdrawal. The
primary end point was overall-response-rate (ORR) as assessed by an
independent review committee (IRC) based on the Lugano
classification.
Key highlights from this manuscript include:
- The ORR was 47.1% across all
relapsed or refractory iNHL patients treated (n=208)
- At a median follow-up of 27.8 months
patients with relapsed or refractory MZL demonstrated:• 49.3%
ORR with 16% Complete response (CR) rate (IRC
assessed)• Median duration of response (DOR) was not reached
(95% CI, 10.3 – not estimable) and• Median Progression Free
Survival (PFS) was not reached (95% CI, 12.1 – not estimable)
- At a median follow-up of 27.5 months
patients with relapsed or refractory FL demonstrated:• 45.3%
ORR with 5.1% achieving a CR (IRC assessed)• Median DOR of
11.1 months (95% CI, 8.3–15.6)• Median PFS was 10.6
months
- Grade ≥3 treatment emergent adverse
events (TEAEs) reported in ≥10% of patients included: neutropenia
(11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥3) occurred
in 6.7%/7.2% of patients.
- Other AEs of special interest
included pneumonitis (1.4%; grade >3 1.0%) and non-infectious
colitis (1.9%; grade >3 0.5%).
- A total of 31 patients (14.9%)
discontinued due to a treatment-related adverse event.
These data are described further in the manuscript
entitled, “Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients with
Relapsed/Refractory Indolent Lymphoma,” which was published online
yesterday in the Journal of Clinical Oncology. The online version
of the article can be accessed
at https://ascopubs.org/doi/full/10.1200/JCO.20.03433.
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 UKONIQTM (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.
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.
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 expectations for the commercial launch and
availability of UKONIQ™ (umbralisib) for relapsed or refractory
(R/R) marginal zone lymphoma (MZL) and follicular lymphoma (FL);
anticipated healthcare professional and patient acceptance and use
of UKONIQ for the FDA-approved indications; and perceptions of the
UNITY-NHL data.
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 Company’s ability to establish and
maintain a commercial infrastructure, and to successfully launch,
market and sell UKONIQ or future products, if approved; failure to
obtain and maintain requisite regulatory approvals, including the
risk that the Company fails to satisfy post-approval regulatory
requirements, such as the submission of sufficient data from a
confirmatory clinical study; 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 profile
and commercial potential of our products; the potential for
variation from the Company’s projections and estimates about the
potential market for UKONIQ or the Company’s product candidates due
to a number of factors, including for example, limitations that
regulators may impose on the required labeling for the proposed
treatment population for UKONIQ or our other product candidates;
the Company’s ability to meet post-approval compliance obligations
(on topics including but not limited to product quality, product
distribution and supply chain, pharmacovigilance, and sales and
marketing); potential regulatory challenges to the Company’s plans
to seek expanded or additional indications for UKONIQ in the U.S.
or plans to seek marketing approval for the product in additional
geographies, outside of the U.S.; the Company’s reliance on third
parties for manufacturing, distribution and supply, and a range of
other support functions for our clinical and commercial products,
including UKONIQ; 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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Investor Relations |
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Email: ir@tgtxinc.com |
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Telephone: 1.877.575.TGTX (8489), Option 4 |
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Media Relations: |
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Email: media@tgtxinc.com |
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Telephone: 1.877.575.TGTX (8489), Option 6 |
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