TG Therapeutics suffered a blow Tuesday morning after it was announced that the FDA would convene an adcomm ahead of the biotech’s upcoming PDUFA appointment for combination blood cancer therapy, which would peg a possible decision.
Although the exact date has not yet been set, regulators plan to hold a meeting of the Oncological Medicines Advisory Committee sometime in March or April, TG said in a press release. Given that timing, the biotech says it is now unlikely for the FDA to make an approval decision by March 25th.
“We look forward to the ODAC meeting as we believe it will be an opportunity for us to highlight the important role U2 can play in the treatment of CLL,” CEO Michael Weiss said in a statement.
In the wake of the news, TG shares soared nearly 45% as the market opened on Tuesday morning.
The program in question is a combination of ubituximab and umbralisib, which the biotech has named U2 (no reference to the Bono-led band). TG is researching therapy to treat adults with chronic lymphocytic leukemia and small lymphoid lymphoma.
According to TG, the FDA is calling ODAC over questions about the overall survival benefits of the program, which the interim analysis failed to analyze, Weiss said in an investor call Tuesday. The OS had been included as a secondary measure but was instead used to measure progression-free survival.
TG provided survival information to regulators as part of the BLA and sNDA review, but Weiss noted that it was not originally included. The CEO said TG and the FDA agreed prior to the study that the survival data would have been too immature and “too small to be meaningful” if the company had tried to measure the OS.
The data that TG eventually provided included an early analysis that showed no statistically significant difference in survival between the treatment arms, Weiss said. He emphasized that the hazard ratio of 1.23 appeared to show an imbalance in favor of the control arm, although the HR decreased to 1.04 when the deaths related to Covid-19 were excluded – again with no statistically significant difference.
Weiss also tried to allay investor concerns about the hearing, stating that there was a “precedent” for approving drugs that appear to favor survival control arms. Citing Roche’s AbbVie and Venclexta as an example, he noted in response to an analyst question that the drug “had no ODAC and the OS was clearly in favor of the GC arm at the time of approval”.
Time will tell if ODAC takes the FDA’s concerns to heart, but the news marks another boost in TG’s quest to get the U2 combo across the finish line – the timing remains up in the air. The biotech was scheduled to read ORR data for therapy in September 2018, but the safety oversight panel said at that point the data was not mature enough.
However, TG brought investors back to the table in May 2020 by exiting positive Phase III results, which showed that the PFS threshold had been reached in an interim analysis. In the full dataset published by ASH in December 2020, TG showed excellent p-values in PFS and ORR (p <0.0001 and p <0.001, respectively), while umbralisib as monotherapy also achieved an overall response rate of 49.3%.