ADC's accelerated review troubles signal FDA's tough new stance on confirmatory studies
ADC Therapeutics seems to have run headlong into the FDA’s new strict policy on accelerated reviews: Get your confirmatory study in line before filing, or wait.
The biotech’s biologics license application for camidanlumab tesirine, or cami, has been pushed back to next year following meetings with the FDA in September and October, ADC said in a third-quarter earnings report. The agency advised that in order for cami to be considered for the accelerated approval path, ADC must have a phase 3 confirmatory study “well underway and ideally fully enrolled” before filing for a BLA.
ADC was hoping to file the therapy for an advanced approval in relapsed or refractory Hodgkin lymphoma following a phase 2 study that showed an overall response rate of 70% and a complete response rate of 33%. Cami would have been ADC's second approval request, after Zynlonta, which nabbed accelerated approval for relapsed or refractory large B-cell lymphoma after two or more lines of treatment.
The company will also pause investments in Hodgkin lymphoma and evaluate options “with a disciplined and strategic approach to resource allocation.” ADC estimates that getting a randomized confirmatory phase 3 enrolled and off the ground would take about two years.
If that’s not enough, ADC also reported that cami in combination with Merck’s Keytruda failed to meet expectations in a phase 1b solid tumor study. The combination showed signs of activity, but the biotech said they ultimately were not enough to continue. The trial will not proceed, but ADC is open to the combo moving forward under the direction of “a partner with immuno-oncology development expertise.”
The FDA’s reluctance to accept cami for accelerated review seems to be a signal of things to come for companies seeking to use this pathway. Therapies can be approved for use early via accelerated approval based on biomarker data that suggest a clinical benefit, and the path is often used for diseases with limited options. Companies must perform a confirmatory trial to seal a full approval.
The pathway was vaulted into the public spotlight last year when the FDA approved Biogen and Eisai’s Alzheimer’s disease drug Aduhelm under it, providing nine years to perform the confirmatory study.
FDA Commissioner Robert Califf, M.D., has spoken out about the need to reform the process and has signaled that he wants confirmatory studies to be in the works earlier, and, ideally, at the time of filing. But the disclosure from ADC appears to be one of the first times that Califf’s idea has been put into action.
In June, BIO Chairman and Nkarta Therapeutics CEO Paul Hastings pushed back against reforms to the accelerated review process, warning that requiring confirmatory trials to be underway before BLA consideration would slow down patients’ access to therapies.
The FDA did not return a request for comment on the new confirmatory study policy as of publication.
ADC continues to work with the FDA on “the potential regulatory path forward” for cami.
Published Nov. 8, 2022
