FDA raises concerns over TG Therapeutics' survival data, plans to convene ODAC
TG Therapeutics took a hit Tuesday morning after announcing the FDA will convene an adcomm ahead of the biotech’s upcoming PDUFA date for a blood cancer combo therapy, throwing a potential decision into limbo.
Though the exact date has not been determined, regulators are looking to hold a meeting of the Oncologic Drugs Advisory Committee sometime in March or April, TG said in a release. Given that timing, the biotech says it’s now unlikely the FDA will reach an approval decision by the March 25 deadline.
“We look forward to the ODAC meeting as we believe it will provide us an opportunity 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 $TGTX cratered by nearly 45% as the market opened Tuesday morning.
The program in question is a combination of ublituximab and umbralisib, which the biotech has referred to as U2 (no relation to the Bono-led band). TG has been researching the therapy to treat adults with chronic lymphocytic leukemia and small lymphocytic lymphoma.
According to TG, the FDA is calling ODAC together over questions about the program’s overall survival benefits, something that was not analyzed in the interim analysis, Weiss said in an investor call Tuesday. OS had been included as a secondary measure, but was instead powered to measure progression-free survival.
TG provided survival info to regulators as part of the BLA and sNDA review, but Weiss noted it was not included originally. The CEO said TG and the FDA had agreed before the study that the survival data would have been too immature and “too small to be informative” had the company attempted to measure OS.
The data TG eventually provided included an early analysis showing no statistically significant difference in survival between the treatment arms, Weiss said. He highlighted that the hazard ratio of 1.23 appeared to show an imbalance in favor of the control arm, though when excluding deaths related to Covid-19, the HR fell to 1.04 — again with no statistically significant difference.
Weiss also attempted to ease investor concerns over the hearing, explaining that there is “precedent” for the approval of drugs that seemingly favor survival control arms. He pointed to AbbVie and Roche’s Venclexta as one example, noting the drug had “no ODAC and OS was clearly in favor of the GC arm at the time of approval,” in response to an analyst question.
Time will tell whether ODAC heeds the FDA’s concerns, but the news marks another bump in TG’s quest to get the U2 combo past the finish line — timing that remains up in the air. In September 2018, the biotech was supposed to read out ORR data for the therapy but the safety monitoring board said at the time the data weren’t mature enough.
TG brought investors back to the table in May 2020, however, reading out positive topline Phase III results that showed it hit the PFS threshold in an interim analysis. In the full dataset revealed at ASH in December 2020, TG showed off stellar p-values in PFS and ORR (p<0.0001 and p<0.001, respectively) while saying umbralisib as a monotherapy also hit a 49.3% overall response rate.