TG Therapeutics, Inc. (NASDAQ: TGTX), today announced data
presentations at the XIX International Workshop on Chronic
Lymphocytic Leukemia (iwCLL). Data highlights from each
presentation are included below.
The Company will also host a virtual investor and analyst event
today, September 20, 2021 at 8:30 AM ET, to review the updated
Phase 1 data evaluating the investigational combination of UKONIQ®
(umbralisib) and ublituximab (U2) plus venetoclax presented at
iwCLL, as well as provide an overview of the ULTRA-V Phase 2/3
trial.
Michael S. Weiss, the Company's Chairman and Chief Executive
Officer, stated, “The iwCLL conference this past weekend was an
exciting meeting, where we were able to share data from four
combination trials, including updated data from our Phase 1/2 study
of U2 plus venetoclax. Our goal has been to develop combination
therapies utilizing U2 as a backbone and we believe the data
presented this weekend showcase the breadth of the program, which
includes combinations with targeted therapy as well as
immunotherapy. With a March 25, 2022 PDUFA date in the US, we are
excited about the potential approval of the U2 regimen for CLL
patients and hope you all can join us this morning for our virtual
event to review some of the encouraging data presented this past
weekend.”
IwCLL 2021 DATA HIGHLIGHTSOral
Presentation Title: Umbralisib Plus
Ublituximab (U2) Is Superior to Obinutuzumab Plus Chlorambucil
(O+Chl) in Patients with Treatment-Naïve (TN) and
Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL):
Results from the Phase 3 UNITY-CLL Study
- 421 patients were randomized to the U2 (n=210) or O+Chl (n=211)
arms; 57% of patients were treatment-naïve and 43% had
relapsed/refractory (R/R) CLL
- At a median follow-up of 36.7 months, U2 significantly
prolonged independent review committee (IRC) assessed
progression-free survival (PFS) vs O+Chl (median 31.9 months vs
17.9 months; hazard ratio 0.546 (p<0.0001))
- PFS improvement with U2 vs O+Chl was consistent across all
subgroups examined including treatment naïve patients (median 38.5
months vs 26.1 months, hazard ratio 0.482) and relapsed/refractory
patients (median 19.5 months vs 12.9 months, hazard ratio
0.601)
- Overall response rate (ORR) was significantly higher with U2
compared to O+Chl (83.3% vs 68.7%; p<0.001)
- For the U2 arm, at a median treatment exposure of 21 months,
most adverse events (AEs) were Grade 1 or 2 in severity and were
relatively balanced between the treatment naïve and previously
treated populations
- Grade 3/4 Adverse Events (AEs) of clinical interest (U2 vs
O+Chl) included elevated ALT (8.3% vs 1.0%), elevated AST (5.3% vs
2.0%), non-infectious colitis (1.9% vs 0%), infectious colitis
(0.5% vs 0.5%), pneumonitis (0.5% vs 0%), rash (2.4% vs 0.5%), and
opportunistic infections (5.8% vs. 1.5%)
Oral Presentation Title: A
Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax in
Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
(CLL)
- Regimen was administered with 3 cycles of U2 as induction in
cycles 1 through 3, U2 plus venetoclax in cycles 4, 5 and 6,
followed by umbralisib plus venetoclax in cycles 7 through 12 in
patients with relapsed or refractory (R/R) CLL. Patients with
centrally confirmed undetectable minimal residual disease (uMRD) in
the bone marrow after cycle 12 were permitted to stop all therapy,
while MRD detectable patients continued on single agent
umbralisib.
- 47 patients have now been treated as of the data cutoff with
57% of patients previously exposed to a BTK inhibitor
- Best Overall Response Rate (ORR) was 100% amongst evaluable
patients (n=46), including 37% complete response (CR) rate
- At cycle 12, 91% of patients (n=34) achieved undetectable
minimal residual disease (uMRD) in the peripheral blood (PB), and
72% of patients (n=32) achieved uMRD in the bone marrow (BM)
- At a median follow up of 24.5 months, median progression-free
survival has not been reached
- Grade 3/4 adverse events (AEs) occurring in >5% of patients
were neutropenia (28%), leukopenia (15%), lymphocytopenia (15%),
infusion related reactions (9%), diarrhea (9%), and anemia (6%). No
TLS events were observed during venetoclax administration
Oral Poster Presentation
Title: TG-1701, a Selective Bruton
Tyrosine Kinase (BTK) Inhibitor, as Monotherapy and in Combination
with Ublituximab and Umbralisib (U2) in Patients with Chronic
Lymphocytic Leukemia
- A total of 50 patients with R/R CLL have been treated with
TG-1701, with patients receiving monotherapy in the dose-escalation
cohort (n=6), 200 mg in a dose-expansion cohort (n=20), 300 mg in a
dose-expansion cohort (n=20), or TG-1701 in combination with U2 in
the dose escalation cohort (n=4).
- TG-1701 monotherapy was well tolerated and the maximum
tolerated dose was not reached up to 400 mg QD.
- Grade 3/4 AEs occurring in patients treated with 200 mg QD of
TG-1701 (n=20), included neutropenia (10%), anemia (5%) and
arthralgia (5%). Grade 3/4 AEs occurring in patients treated with
300 md QD of TG-1701 (n=20), included neutropenia (20%), COVID-19
(5%), ALT increased (5%) and AST increased (5%).
- 100% ORR observed in the 300 mg QD monotherapy expansion cohort
at a median follow up of 12 months (n=19)
- 95% ORR observed in the 200 mg QD monotherapy expansion cohort
at a median follow up of 19 months (n=20)
- 100% ORR observed in the 1701+U2 dose escalation (using doses
of 100 mg to 300 mg QD of TG-1701) at a median follow up of 19
months (n=3)
Poster Presentation Title:
Phase I/II Study of Umbralisib (TGR-1202), Ublituximab (TG-1101),
and Pembrolizumab in Patients with Relapsed or Refractory Chronic
Lymphocytic Leukemia and Richter’s Transformation: 5-Year
Follow-up
- A total of 20 patients with R/R CLL or Richter’s Transformation
(RT) were treated with the triple combination of ublituximab,
umbralisib, and pembrolizumab. Patients with CLL received 2
cycles of the U2 regimen before pembrolizumab was added for an
additional 4 cycles, followed by umbralisib maintenance. Patients
with RT received U2 + pembrolizumab for the first 4 cycles,
followed by U2 maintenance. Twenty patients
were evaluable for safety (11 CLL patients and 9 RT patients) and
19 were evaluable for efficacy (11 CLL and 8 RT).
- The triple combination was well tolerated, with immune mediated
toxicities not appearing above what would be expected with either
umbralisib or pembrolizumab alone. Grade 3/4 AEs occurring in
>20% of patients (n=20) include, neutropenia (45%),
thrombocytopenia (15%), ALT increase (15%), leukopenia (10%),
nausea (5%), fatigue (5%), and anemia (5%).
- In this heavily pre-treated cohort with a median of 2 (1-9)
prior lines of therapy: -- 91% ORR in patients with R/R
CLL (n=11)-- 83% ORR in BTK refractory CLL patients
(n=6), with 4 of 5 responders achieving a response to U2 alone at
the patient’s first efficacy assessment, prior to the addition of
pembrolizumab -- 25% ORR in patients with RT (n=8),
including 25% CR rate
The above data presentations are available on the Publications
page, located within the Pipeline section, of the Company’s website
at www.tgtherapeutics.com/publications.cfm.INVESTOR &
ANALYST VIRTUAL EVENT INFORMATIONThe Company will host a
virtual event today, September 20, 2021 at 8:30 AM ET, to discuss
the updated Phase 1 data evaluating UKONIQ® (umbralisib) and
ublituximab (U2) in combination with venetoclax in patients with
CLL as well as provide an overview of the Phase 2/3 ULTRA-V
program.
To attend the live event, please visit the Events page, located
within the Investors & Media section, of the Company's website
at http://ir.tgtherapeutics.com/events. Following the live event,
an archive file will be available for replay, for a period of 30
days after the call.ABOUT U2 PLUS VENETOCLAX PHASE 1
TRIALThe Phase 1/2 trial, (NCT03379051), is a
multi-center, dose-escalation trial designed to assess the safety
and efficacy of UKONIQ and ublituximab (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 overall response rate (ORR), including complete response
(CR) rate, progression-free survival (PFS), and undetectable
minimal residual disease (uMRD) rate after 12 cycles of therapy.
The trial enrolled approximately 50 CLL patients and is being led
by Dr. Paul Barr of the Wilmot Cancer Institute, University of
Rochester Medical Center.
ABOUT ULTRA-V PHASE 2 TRIALThe ULTRA-V Phase 2
trial, (NCT03801525), is an open-label, multicenter, trial designed
to investigate the efficacy and safety of UKONIQ and ublituximab
(U2) 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 ULTRA-V PHASE 3 TRIALThe 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 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.
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 our clinical
programs, including our clinical trials evaluating the
investigational combination of UKONIQ® (umbralisib) and ublituximab
(U2) plus venetoclax.
Any forward-looking statements in this press release are based
on management's current expectations and beliefs and are subject to
a number of risks, uncertainties and important factors that may
cause actual events or results to differ materially from those
expressed or implied by any forward-looking statements contained in
this press release. In addition to the risk factors identified from
time to time in our reports filed with the U.S. Securities and
Exchange Commission (SEC), factors that could cause our actual
results to differ materially include the following: the risk that
interim, top-line or other early clinical trial results, that may
have supported the acceptance of our data for presentation or
influenced our decision to proceed with additional clinical trials,
will not be reproduced in final data sets or in future studies; the
risk that the safety profile observed with umbralisib, ublituximab
or TG-1701, or combinations thereof, may change as additional
patients are exposed for longer durations; the risk that the U2
combination will not prove to be a safe and efficacious
combination, or backbone for triple therapy combinations, including
with venetoclax and TG-1701; the risk that the clinical development
of our products and regimens will take longer and/or cost more than
planned; the uncertainties inherent in research and development;
the risk that the clinical results from our registrational trials
will not support regulatory approval of our investigational
products or regimens, including the risk that FDA will not approve
ublituximab in combination with umbralisib for the treatment of
CLL; the risk that if approved, our products will not be
commercially successful; 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 SEC.
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.com
Telephone: 1.877.575.TGTX (8489), Option 6
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