Full Press Release Details
TG Therapeutics Announces Positive Topline Data from Phase 3
GENUINE Study of TG-1101 in Combination with Ibrutinib in Patients
with High Risk Chronic Lymphocytic Leukemia (CLL)
Study met its primary endpoint, with TG-1101 (ublituximab) plus
ibrutinib increasing Overall Response Rate (ORR) by >70% over
The combination was well tolerated with a safety profile consistent
with the Phase 2 study of ublituximab plus ibrutinib recently
published in the British Journal of Haematology
Targeting full data presentation at a medical meeting in 1H17 and
meeting with FDA in 2H17 to discuss the results and filing for
accelerated approval
Conference call to be held today, Monday March 6,
2017 at 8:30 am ET, with Dr. Anthony Mato from the
University of Pennsylvania, a lead enroller in the GENUINE
New York, NY, March 6, 2017 TG Therapeutics
(NASDAQ:TGTX) today announced positive topline results from its
Phase 3 GENUINE clinical trial of TG-1101 (ublituximab) plus
ibrutinib in patients with previously treated high risk Chronic
Lymphocytic Leukemia (CLL). For the study, high risk was defined as
having any one or more of the following: 17p deletion, 11q deletion
The multicenter, randomized trial (NCT02301156), which assessed the
efficacy and safety of TG-1101 plus ibrutinib, met its primary
endpoint, demonstrating a statistically significant improvement in
Overall Response Rate (ORR) compared to ibrutinib alone in both the
Intent to Treat (ITT) population (p=0.001) and Treated population
(p<0.001). The ITT population includes all 126 randomized
patients (64 in the TG-1101 + ibrutinib arm and 62 in the ibrutinib
alone arm) while the Treated population includes all ITT patients
that received at least one dose of either study drug (59 in the
TG-1101 + ibrutinib arm and 58 in the ibrutinib alone
Overall Response Rates
| TG-1101 plus Ibrutinib | Ibrutinib | P-value | |
| Treated Population (n) | n=59 | n=58 | |
| Overall Response Rate | 80% | 47% | P<0.001 |
responses were assessed by independent blinded central review using
the iwCLL 2008 guidelines. Per iwCLL guidelines, responders require
confirmation of response for a minimum duration of 2 months. As of
the date of the analysis, each arm had responders that were
awaiting confirmation visits which are scheduled to occur over the
next two months. During the study it was infrequent (less than 3%
in the combination arm) for initial responses to fail to be
confirmed. Median follow-up for the study was approximately 12
GENUINE study was designed to demonstrate the value of adding
TG-1101, a highly potent next
generation glycoengineered anti-CD20 monoclonal antibody to
ibrutinib monotherapy in high risk CLL, and was powered to show a
statistically significant improvement in ORR, with a minimal
absolute detectable difference between the two arms of
approximately 20%. The absolute difference between the arms was
approximately 30% resulting in a p-value of < 0.001. Results from
registration directed studies included in the ibrutinib prescribing
information demonstrate single agent ibrutinib response rates
ranging from 43% to 58% in patients with previously treated CLL,
with the findings from the GENUINE study of 47% ORR for ibrutinib
fitting well within historical experience.
In addition to ORR, observed advantages were seen for the
combination in a number of secondary and other efficacy measures,
including radiographic Complete Response (CR) rate, Progression
Free Survival and Time to Response. Sufficient data on MRD
negative status and bone marrow confirmation of radiographic CRs
were not available at the time of analysis. From a safety
standpoint, the combination was well tolerated with a safety
profile consistent with the Phase 2 study of ublituximab plus
ibrutinib recently published in the British Journal of
A full analysis of the Phase 3 GENUINE data along with detailed
efficacy and safety results will be submitted for presentation at a
medical meeting in the first half of 2017 and the Company plans to
meet with the FDA as soon as possible thereafter to discuss the
filing of the data for accelerated approval.
"TG-1101 is a highly potent next generation glycoengineered
anti-CD20 monoclonal antibody. We believe the data today
demonstrate that the addition of TG-1101 to ibrutinib enhances the
therapeutic benefit of ibrutinib in patients with previously
treated high risk CLL, the patient population with the poorest
outcome on ibrutinib. We believe the results observed in the
combination arm are extremely compelling and the regimen has the
potential to become the standard of care for treating patients with
high risk CLL that have progressed from other therapies," said
Michael S. Weiss, Executive Chairman and Chief Executive Officer of
TG Therapeutics. Mr. Weiss continued, "We believe that using
combination therapy to accelerate and deepen response in poor
prognosis high risk CLL is critically important for patient
outcomes and we look forward to sharing these data with the FDA in
the coming months to discuss filing for accelerated approval. Most
importantly, we would like to thank the investigators and their
patients for participating in this significant
Jeffrey Sharman, the GENUINE Phase 3 Study Chair and the Medical
Director for Hematology Research for the US Oncology Network,
commenting on the results stated, Ibrutinib has been a great
addition to our CLL armamentarium, however we have long believed
that ibrutinib alone may not be enough, particularly for patients
with high-risk disease. This study demonstrates that the
addition of ublituximab, can significantly enhance the response
rates without compromising safety. We believe that the rapid
responses seen in our Phase 2 study with ublituximab plus ibrutinib
are validated here in our Phase 3 GENUINE study and are important
markers of improved overall efficacy and patient outcomes. I
look forward to the presentation of the results at an upcoming
ABOUT THE PHASE 3 GENUINE STUDY
The Phase 3 GENUINE study is a randomized, open label, multicenter
clinical trial to evaluate the safety and efficacy of TG-1101
(ublituximab) plus ibrutinib compared to ibrutinib alone in adult