- Shares in TG Therapeutics Inc. fell nearly 16% Monday after the biotech provided an update on a meeting with the Food and Drug Administration to discuss a potential filing for accelerated approval of its blood cancer combination therapy next year.
- According to the company, the FDA said using overall response rate (ORR) data from TG's GENUINE Phase 3 study of ublituximab combined with ibrutinib to obtain conditional approval would be classified as a "review issue" — e.g., a substantive concern that could impact the regulator's ability to issue an approval.
- TG had altered the study protocol for GENUINE last year, cutting the trial's enrollment and making ORR the trial's sole primary endpoint. As part of the recent meeting, the FDA suggested TG consider future available therapies in its analysis for any potential Biologics License Application aimed at accelerated approval.
GENUINE paired TG's ublituximab with AbbVie Inc.'s Imbruvica (ibrutinib) in adults with previously treated, high-risk chronic lymphocytic leukemia (CLL), testing whether adding TG's drug would improve on Imbruvica's efficacy.
The changes in the study protocol last October accelerated the trial's timeline, but necessitate review with the FDA to ensure any future application's acceptability.
"We had a very productive meeting with the FDA regarding the GENUINE study and its use for approval of TG-1101 in combination with ibrutinib," said company CEO Michael Weiss in a Oct. 16 statement. "We look forward to our follow-up meeting and working with the FDA in an effort to reach an agreement on the potential use of PFS for full approval in a similar timeframe as accelerated approval."
The recent meeting, as Weiss noted, also focused on the possible use of progression-free survival (PFS) from the GENUINE study for full approval. This will be discussed further in a meeting with the FDA before the end of 2017, TG said.
This apparent willingness to consider use of PFS for full approval could be a positive, despite the concerns over a potential regulatory snag, wrote Jefferies analyst Matthew Andrews in a Oct. 17 note. The elimination last year of a study arm aimed at PFS meant GENUINE is no longer powered for detecting a benefit on that measure. If the FDA is more flexible on this matter, Andrews suggests, that could be a positive for the company.
TG said it plans to monitor the market for new approvals of agents for CLL, and hopes to submit a BLA in second quarter 2018.
TG stock lost nearly a fifth of its value last year when the company altered the GENUINE study and cut patient enrollment. While the company now has positive data in hand, the impact of those changes on the regulatory process is now being felt.
Also on Monday, TG announced it has completed enrollment of its UNITY-CLL Phase 3 trial which combines ublituximab with the company's PI3K delta inhibitor umbralisib in treatment-naïve and relapsed or refractory CLL patients.
The study, conducted under a special protocol assessment agreement, will compare the combination with Roche's Gazyva (obinutuzumab) plus chlorambucil. Top-line data from that study are expected in the second quarter of 2018, with a potential new drug application for the combination in the second half of next year. If this timeline holds, submissions for the two combinations based on GENUINE and UNITY could come very close together.