The troubles are stacking up for TG Therapeutics' U2 cancer combo. The FDA has told the biotech to stop enrolling patients in certain trials for various cancers, which comes on top of a planned advisory committee meeting scheduled for March or April and after the agency requested more data for the regulatory filing in November.
The news could be summed up by a one-word U2 song: "Bad." Jefferies analysts noted the partial clinical hold, disclosed at an investor conference Thursday, "is not a good signal, but we do not think it will affect ongoing studies." It surely affected the biotech's stock: TG's shares were down 43% to around $8 apiece in pre market trading Friday morning.
U2 is a combination of TG's approved relapsing lymphoma med Ukoniq and an investigational treatment called ublituximab. The duo is being tested across multiple studies in patients with chronic lymphocytic leukemia, CLL, and non-Hodgkin lymphoma, or NHL.
The combo is in a midstage trial for NHL and two phase 3 studies in CLL. TG is also testing the drug combo with AbbVie and Roche's Venclexta in another midstage trial in CLL. Further yet, the duo is paired with investigational med TG-1701 in a phase 1 trial in CLL and NHL.
But, here's the dinger: TG won't say which of those studies were hit with the partial clinical hold. The biotech did disclose, though, that "most studies" impacted by the FDA's decision had already been closed to new enrollment or the company had put them on administrative hold.
Jefferies analysts said they'll keep their eyes peeled on the triple combination study with Venclexta. That trial, dubbed ULTRA-V, is "likely very important for commercial success in this indication," the analysts wrote, referring to CLL. The phase 3 trial is paused until the outcome of the advisory committee meeting, the analysts said.
U2 has been under regulator scrutiny since November when the FDA asked to see more data on the phase 3 UNITY-CLL trial before a decision on the combo could be made. The FDA set up an advisory committee meeting for March or April to discuss the drug.
Now, TG says it was close to completing a submission of the requested updated overall survival (OS) data to the FDA, which improved from the preliminary data disclosed on Nov. 30 but still wasn't statistically significant. The drug met its main objective of progression-free survival by beating out the control arm, which included Roche's Gazyva along with chemotherapy chlorambucil, but the FDA wanted additional data on OS, a secondary efficacy goal.
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The drug combo had an OS hazard ratio of 1.23, or 1.04 when removing data from patients who died due to COVID-19. A ratio above 1 implies the therapy is potentially causing harm.
While some of the studies were put on partial clinical hold, some patients might be able to continue on the combo therapy if they are "deriving clinical benefit" after being reconsented, TG said.