New York, November 30, 2021 (Global News Agency)-TG Therapeutics, Inc. (NASDAQ: TGTX) today announced that the U.S. Food and Drug Administration (FDA) has notified the company of its plans to host an oncology The Pharmaceutical Advisory Committee (ODAC) for its review of the pending biologics licensing application (BLA)/supplemental new drug application (sNDA) for the combination of ublituximab and UKONIQ® (umbralisib) (combination referred to as U2) has chronic lymphocytic leukemia Adult patients with (CLL) and small lymphocytic lymphoma (SLL).

Michael S. Weiss, Chairman and CEO of TG Therapeutics, said: "We thank the FDA for its efforts in reviewing U2 BLA/sNDA and its interest in obtaining ODAC's views on the benefits-risks of the combination of UKONIQ and U2. We believe in UKONIQ is a unique PI3K inhibitor with different toxicity and tolerability characteristics, and it is believed that the data submitted so far supports the approval of U2 in CLL.” Mr. Weiss continued, “We look forward to the ODAC meeting because we believe It will provide us with an opportunity to emphasize the important role that U2 can play in the treatment of CLL. As we pointed out before, although many CLL patients are well served in the currently available therapies, there is a lack of service Of the population, for a variety of reasons, including tolerance issues, access issues and treatment failures, they will benefit from alternative treatment options."

About ODAC meetings Generally speaking, ODAC will review and evaluate data on the safety and effectiveness of marketed and under-development human drug products for the treatment of cancer, and make appropriate recommendations to the Food and Drug Commissioner. Although the FDA will consider the ODAC committee's recommendations, the final decision on product approval is entirely made by the FDA. 

The FDA has notified the company that potential problems and discussion topics of ODAC include: the benefits and risks of U2 combination treatment of CLL or SLL, and the benefits and risks of UKONIQ in relapsed/refractory marginal zone lymphoma (MZL) or follicular lymphoma (FL). In addition, as part of the benefit-risk analysis, the overall safety of the U2 regimen is expected to be reviewed, including adverse events (serious and grade 3-4), discontinuations and dose adjustments caused by adverse events. The FDA’s concerns about the ODAC meeting seem to stem from an early analysis of the overall survival of the UNITY-CLL trial.

Overall survival was designated as a secondary efficacy outcome in the UNITY-CLL protocol, but it was not part of the primary analysis based on the statistical analysis plan of the study agreed through the Special Protocol Evaluation (SPA), so it was not analyzed or included in the BLA/sNDA . In addition, the study is not sure about overall survival. As part of the ongoing BLA/sNDA review, the FDA requires an early analysis of the overall survival of the UNITY-CLL trial. As of September 2021, the deadline for the overall survival analysis required by the FDA during its review period, it is conducive to the imbalance in the control group (HR: 1.23) although this result is not statistically significant. However, when COVID-19-related deaths were excluded, the two groups were roughly balanced (HR: 1.04), and there was no statistically significant difference in overall survival between the treatment groups. The overall survival results are preliminary. As more events emerge, the company will continue to evaluate this endpoint and continue to analyze how COVID-19 may affect the analysis.

The date of the ODAC meeting has not yet been determined, although the FDA has stated that its goal is to hold ODAC in March or April 2022. Given this time, we believe that it is unlikely that the FDA will sNDA with a BLA/PDUFA target date of March 25, 2022.   

About UNITY-CLL Phase 3 trial and BLA/sNDA submission UNITY-CLL is a global phase 3 randomized controlled clinical trial that compares the combination of ublituximab plus UKONIQ (umbralisib) or U2 with the active control group of obinutuzumab Mustard is used to treat patients with newly treated and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomly divided patients into four treatment groups: ublituximab single-agent, UKONIQ single-agent, ublituximab plus UKONIQ, and an active control group of obinutuzumab plus chlorambucil. A pre-specified interim analysis was performed to evaluate the contribution of ublituximab and UKONIQ in the U2 combined arm and to allow termination of the single-agent arm. Therefore, the UNITY-CLL Phase 3 trial continues to include two combination groups at a 1:1 ratio: the U2 study group and the obinutuzumab plus chlorambucil control group. Approximately 420 subjects participated in the two combination treatment groups, approximately 60% of patients had not received treatment, and 40% of patients relapsed or refractory to treatment. The primary endpoint of this study is that the U2 combination has a higher progression-free survival (PFS) compared to the control group. The trial reached its primary endpoint. At a median follow-up of 36.7 months, U2 significantly extended PFS and controls assessed by the Independent Review Committee (IRC) (median 31.9 months vs. 17.9 months; hazard ratio 0.546 (p< 0.0001)), and the results have been announced at the American Society of Hematology (ASH) annual meeting in December 2020. The UNITY-CLL Phase 3 trial is underway under a Special Agreement Evaluation (SPA) agreement with the U.S. Food and Drug Administration (FDA).

U2 BLA/sNDA submission for the treatment of CLL is based on the results of the UNITY-CLL trial. The FDA previously granted U2 combination fast track designation for the treatment of adult CLL patients, and the combination of ublituximab and UKONIQ for the treatment of CLL orphan drug designation. On May 25, 2021, the FDA accepted U2's BLA as a treatment for patients with CLL and SLL, and set the target date for the Prescription Drug User Fee Act (PDUFA) as March 25, 2022. About Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia (CLL) is the most common type of adult leukemia. It is estimated that there will be more than 20,000 newly confirmed CLL cases in the United States in 2020, and approximately 45,000 newly confirmed cases worldwide in 2020. 1,2 Although the signs and symptoms of CLL may disappear within a period of time after initial treatment, the disease is considered incurable, and due to the return of malignant cells, many people will require additional treatment.

Conference call information The company will host a conference call today (November 30, 2021) at 8:30 am Eastern Time to discuss regulatory updates.

To participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside U.S.), conference name: TG Therapeutics Update Call. The "Events" page in the "Investors and Media" section of the company's website http://ir.tgtherapeutics.com/events will provide live audio webcasts. The recording of the conference call will also be available within 30 days after the end of the conference call. About TG THERAPEUTICS TG Therapeutics is a fully integrated commercial-stage biopharmaceutical company focused on the acquisition, development and commercialization of new therapies for B-cell malignancies and autoimmune diseases. In addition to an active research pipeline that includes five investigational drugs across these therapeutic areas, TG has also received accelerated approval from the U.S. FDA for UKONIQ® (umbralisib) for the treatment of adult patients with relapsed/refractory marginal zone lymphoma These patients have received at least one previous anti-CD20-based regimen and relapsed/refractory follicular lymphoma, and have received at least three previous systemic treatments. Currently, the company has three projects in phase 3 development for the treatment of patients with relapsing multiple sclerosis (RMS) and chronic lymphocytic leukemia (CLL), as well as some investigational drugs in phase 1 clinical development. For more information, please 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) δ and casein kinase 1 (CK1) ε. It is known that PI3K-delta plays an important role in supporting cell proliferation and survival, cell differentiation, cell-to-cell transport and immunity, and is expressed in normal and malignant B cells. CK1-epsilon is a regulator of oncoprotein translation and is related to the pathogenesis of cancer cells, including lymphoid malignancies. UKONIQ is suitable for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have previously received at least one anti-CD20 regimen, as well as for the treatment of relapsed or refractory follicular lymphoma (FL) Adult patients have received at least three previous systemic treatments. These indications were approved under accelerated approval based on the overall response rate. Continued approval for this indication may depend on the verification and description of clinical benefits in confirmatory trials.

Important safety information Infection: Patients treated with UKONIQ have serious, including fatal infections. 10% of the 335 patients had grade 3 or higher infections, and the incidence of fatal infections was <1%. The most common infections of grade ≥3 include pneumonia, sepsis, and urinary tract infections. Provide prevention of Pneumocystis pneumonia (PJP), and consider preventive antiviral drugs during treatment with UKONIQ to prevent CMV infection, including CMV reactivation. Monitor any new or worsening signs and symptoms of infection during treatment with UKONIQ, including suspected PJP or CMV. For grade 3 or 4 infections, UKONIQ is not given until the infection is resolved. Resume UKONIQ at the same or reduced dose. UKONIQ is not given to patients with suspected PJP of any grade, and it is permanently terminated in patients with confirmed PJP. For clinical CMV infection or viremia, do not give UKONIQ until the infection or viremia resolves. If UKONIQ is restored, give the same or reduced dose and monitor the patient's CMV reactivation by PCR or antigen testing at least monthly. Neutropenia: Patients treated with UKONIQ developed severe neutropenia. Of the 335 patients, 9% had grade 3 neutropenia, and 9% had grade 4 neutropenia. Monitor the neutrophil count at least every 2 weeks for the first 2 months of UKONIQ, and in patients with neutropenia during treatment with UKONIQ that the neutrophil count is less than 1 x 109/L (grade 3-4) Monitor at least once a week. Consider supportive care as appropriate. According to the severity and persistence of neutropenia, withhold, reduce the dose or discontinue UKONIQ. Diarrhea or non-infectious colitis: Patients treated with UKONIQ have severe diarrhea or non-infectious colitis. 53% of the 335 patients had any grade of diarrhea or colitis, and 9% of the patients had grade 3. For patients with severe diarrhea (Grade 3, that is,> 6 bowel movements per day) or abdominal pain, mucus or blood in the stool, changes in bowel habits, or peritoneal signs, UKONIQ will not be given until resolved and provided with antidiarrheal drugs or enteric-coated drugs Use steroids as appropriate for supportive care. After resolution, resume UKONIQ with a reduced dose. For any grade of recurrent grade 3 diarrhea or recurrent colitis, discontinue UKONIQ. Discontinue UKONIQ for life-threatening diarrhea or colitis. Hepatotoxicity: Severe hepatotoxicity occurred in patients treated with UKONIQ. Among 335 patients, the incidence of grade 3 and 4 elevated transaminases (ALT and/or AST) were 8% and <1%, respectively. Monitor liver function at baseline and during treatment with UKONIQ. For ALT/AST greater than 5 times to less than 20 times ULN, do not give UKONIQ until recovery to less than 3 times ULN, and then resume with a reduced dose. For ALT/AST elevations greater than 20 times the ULN, discontinue UKONIQ. Severe skin reactions: Patients treated with UKONIQ experienced severe skin reactions, including a fatal case of exfoliative dermatitis. Grade 3 skin reactions occurred in 2% of 335 patients, including exfoliative dermatitis, erythema, and rash (mainly maculopapular rash). Monitor patients for new or worsening skin reactions. Check all concomitant medications and stop any medications that might work. Do not give UKONIQ for severe (grade 3) skin reactions until resolved. Monitor at least once a week until it is resolved. After resolution, resume UKONIQ with a reduced dose. If severe skin reactions do not improve, worsen, or recur, discontinue UKONIQ. Stop using UKONIQ due to a life-threatening skin reaction or any level of SJS, 10 or DRESS. Provide supportive care as appropriate. Allergic reactions caused by the inactive ingredient FD&C Yellow No. 5: UKONIQ contains FD&C Yellow No. 5 (Tartrine Yellow), which may cause allergic reactions (including bronchial asthma) in certain susceptible people, and is common in patients allergic to aspirin . Embryo-fetal toxicity: Based on findings in animals and its mechanism of action, administering UKONIQ to pregnant women can cause harm to the fetus. Inform pregnant women of the potential risks to the fetus. It is recommended that women and men with female partners of reproductive potential use effective contraception during treatment and at least one month after the last dose. Serious adverse reactions occurred in 18% of the 221 patients treated with UKONIQ. Serious adverse reactions that occurred in ≥ 2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). 14% of patients permanently discontinued UKONIQ due to adverse reactions. 11% of patients reduced the dose of UKONIQ due to adverse reactions. 43% of patients discontinued the dose of UKONIQ due to adverse reactions. Among the 221 patients treated with UKONIQ, the most common adverse reactions (>15%), including laboratory abnormalities were increased creatinine (79%), diarrhea-colitis (58%, 2%), fatigue (41%) ), nausea (38%), neutropenia (33%), increased ALT (33%), increased AST (32%), musculoskeletal pain (27%), anemia (27%), thrombocytopenia ( 26%), upper respiratory tract infection (21%), vomiting (21%), abdominal pain (19%), decreased appetite (19%) and skin rash (18%). Lactation period: Since umbralisib may have serious adverse reactions in breastfed children, women are advised 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 complete prescription information and medication guidelines.

1 Cancer statistics: Leukemia-Chronic Lymphocytic Leukemia (CLL). National Cancer Institute Surveillance, Epidemiology, and Final Results Program website. https://seer.cancer.gov/statfacts/html/clyl.html. Visited on October 26, 2020. 2 EpiCast report: Chronic Lymphocytic Leukemia-Epidemiological predictions to 2025. Available from the following URL: https://store.globaldata.com/report/gdhcer164-17-epicast-report-chronic-lymphocytic-leukemia-epidemiology-predicted to 2025/. Cautionary Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the BLA/sNDA submission of ublituximab and UKONIQ® (umbralisib). This is an ODAC meeting planned by the FDA to review the UKONIQ bill Benefits-risks of drug therapy and combination with ublituximab, FDA review and potential approval of BLA/sNDA and its timing, potential benefits, safety and effectiveness of ublituximab combined with UKONIQ in CLL, clinical development of our product candidates, and expected milestones. In addition to the risk factors identified from time to time in our report to the US Securities and Exchange Commission, the factors that may cause significant differences in our actual results are as follows: FDA will not approve the risk of BLA/sNDA submission; FDA will withdraw UKONIQ for the treatment of recurrence Or the risk of approval of refractory MZL or FL; safety issues or trends observed in the UNITY-CLL study, including the incidence of serious adverse events and adverse events of grade 3 or higher, and the rate of discontinuation caused by adverse events The risk of dose adjustment caused by adverse events and adverse events will prevent the joint approval of ublituximab with UKONIQ or, if approved, will lead to REMS or other risk management measures; after further analysis of the data from the UNITY-CLL study, the company will voluntarily withdraw ublituximab and UKONIQ The risk of the combined BLA/sNDA; the risk of unfavorable results of the ODAC meeting, or even if it is favorable, the FDA does not approve the U2 combination or approve or impose certain restrictions or warnings in the narrower sense of the population, which has a negative impact on the commercial potential of U2 in CLL. UKONIQ is currently Approved indications, or any future indications for UKONIQ or ublituximab; risk of FDA not taking action on BLA/sNDA before the PDUFA target date March 25, 2022; overall survival from UNITY-CLL included in this press release The risk of negative changes in data with additional analysis and time; FDA disagrees with the company’s assessment of the impact of COVID-19-related deaths on the overall survival analysis proposed in this press release; if approved, ublituximab and UKONIQ or Any other candidate product portfolio will not be commercially successful; the differential tolerance characteristics of UKONIQ previously observed in clinical trials will not be a risk that will be reproduced in the UNITY-CLL trial or any other ongoing research, or The FDA will not agree with our interpretation of the safety of UKONIQ, ublituximab, or any of our drug candidates; our ability to successfully and cost-effectively complete preclinical and clinical trials, including clinical trials involving the U2 program; Certainty; and the risk that the ongoing COVID-19 pandemic and related government control measures will adversely affect our R&D plans or commercialization efforts.

Further discussion of these and other risks and uncertainties can be found in our annual report on Form 10-K for the fiscal year ending December 31, 2020, which is updated by our subsequent quarterly report on Form 10-Q, and Among the other documents we filed with the US Securities and Exchange Commission. Any forward-looking statements made in this press release are only effective 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 this date.

This press release and previous versions are available at www.tgtherapeutics.com. The information on our website has not been incorporated into this press release by reference and is for reference only. get in touch with:

Investor Relations Email: ir@tgtxinc.com Tel: 1.877.575.TGTX (8489), option 4

Media Relations: Email: media@tgtxinc.com Phone: 1.877.575.TGTX (8489), option 6

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