Freeline Therapeutics slams the brakes on gene therapy trial plans as FDA seeks more clarity on manufacturing
Freeline Therapeutics is joining a growing lineup of companies called to account for CMC issues while walking its gene therapy candidate through clinical trials.
The UK-based biotech’s stock $FRLN slipped nearly 2% on Monday morning after the company announced it’s delaying plans for a pivotal trial by two years in order to work on CMC feedback from the FDA. The hemophilia B program, dubbed FLT180a, was initially slated to enter a pivotal Phase IIb/III study in the second half of this year.
“The modification to the FLT180a clinical development plan is intended to address feedback Freeline received from the (FDA) relating to the characterization and comparability of the investigational drug product used in its Phase 1/2 B-AMAZE trial that was produced at smaller scale, as compared to its current investigational drug product that is produced at commercial scale,” Freeline said in a statement.
Despite the setback, Freeline says it can remain on track by conducting dose confirmation in an ongoing Phase I/II trial, instead of Phase IIb as originally planned. The dose-escalation portion is expected to launch by the end of 2021. It’ll be a six-month, single-dose safety and efficacy trial with a data readout by the end of 2022.
Freeline plans on initiating a pivotal Phase III trial by mid-2023, which would set it up to approach regulators by the end of 2024 if the data pan out. The late-stage study would be “nearly identical” to the old Phase III portion of the previously planned Phase IIb/III, according to the company.
“We believe conducting dose confirmation in a Phase 1/2 trial should allow us to achieve similar objectives as our previously planned trial, whilst also enabling us to work with FDA on CMC prior to initiating the Phase 3 pivotal trial,” CEO Theresa Heggie said in a statement. “To streamline the development path for our subsequent programs, we have developed our entire pipeline from Phase 1 onward using the same commercial-scale manufacturing platform that we are now using for FLT180a.”
Hemophilia is a genetic bleeding disorder in which a protein made by the body to help clot blood is either partly or completely missing (also known as a clotting factor). In hemophilia B, there is a deficiency of the clotting Factor IX protein.
Back in December, Freeline announced that FLT180a showed “durable Factor IX activity” up to a period of nearly three years, with no bleeds reported requiring FIX supplementation in the Phase I/II B-AMAZE study. The company also said it had an “End of Phase II” meeting with the FDA in November, which suggested it was on a “clear path” to begin the pivotal Phase IIb/III by the end of this year.
Freeline isn’t the only gene therapy player to be hampered by CMC issues. Bluebird bio, BioMarin and Voyager have also run into their own problems. A couple months ago, bluebird pushed back the filing for its gene therapy in sickle cell disease by a year due to a new data requirement from the FDA.