On September 15, 2014 TG Therapeutics reported that it has reached an agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design, endpoints and statistical analysis approach of a Phase 3 clinical trial for TG-1101 (ublituximab), its glycoengineered anti-CD20 monoclonal antibody, in combination with Imbruvica (ibrutinib) for the treatment of Chronic Lymphocytic Leukemia (CLL) in patients with high risk cytogenetics (Press release TG Therapeutics, SEP 15, 2014, View Source [SID:1234500747]). The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that would support the regulatory submission for drug approval.

Full details of the Phase 3 clinical trial will be released at the launch of the study, which is expected to occur before the end of the year. In this randomized controlled trial, patients will receive either TG-1101 plus ibrutinib or ibrutinib alone. The trial will enroll approximately 330 patients, with approximately the first two-thirds of the patients included in the ORR assessment. As per the SPA, the Company plans to use the ORR data from the trial as the basis for submission of a Biologics License Application (BLA) for accelerated approval for TG-1101. All patients will then be followed for PFS assessment, which is designed to support full approval.

Additionally, the Company reported that enrollment into the CLL cohort of its ongoing combination Phase 2 study of TG-1101 plus ibrutinib is now closed. The Company expects it will have over 30 CLL patients evaluable for safety and efficacy available for presentation at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) this December.

Dr. Jeff Sharman, Medical Director of Hematology Research for the US Oncology Network, and currently the lead investigator on the Company’s Phase 2 combination trial of TG-1101 plus ibrutinib, will be the Study Chair for this Phase 3 trial. Dr. Sharman commented, “We have been very pleased with the safety and activity profile of the combination seen thus far in our Phase 1/2 trial, and are excited to lead this important clinical trial. Combining a glycoengineered anti-CD20 monoclonal antibody with ibrutinib has the potential to materially increase the number of patients benefitting from treatment with ibrutinib therapy. The Phase 2 trial has enrolled very quickly throughout our clinical research network with patients, physicians, and nurses recognizing the benefits of this study.”

Michael S. Weiss, Executive Chairman and Interim Chief Executive Officer of TG Therapeutics, stated, “The TG-1101 SPA agreement is a major milestone for us as it represents the first clearly defined development and regulatory pathway for the approval of TG-1101 for the treatment of CLL. As we’ve mentioned previously, reaching agreement with the FDA on this combination trial with ORR as a primary endpoint for accelerated approval was our number one priority. We are thrilled to get this first SPA in place earlier than anticipated, which puts us in an excellent position to build out the remainder of our registration program for both TG-1101 and TGR-1202. We would like to thank the FDA for its invaluable guidance throughout this process. The speed at which the FDA reviewed the submission demonstrates a real commitment to drive novel medicines to the patients who need them as rapidly as possible.” Mr. Weiss continued, “We look forward to launching this trial by year end and are excited to continue to work with Dr. Sharman, the entire US Oncology team, and all investigators, who have been instrumental in our development of this important combination.”