Drugmakers developing experimental multiple myeloma drugs may have a quicker path to market under new guidance the Food and Drug Administration published this week.
According to the new framework, the regulator may grant accelerated approvals in some settings based on a therapy’s ability to induce “minimal residual disease” or “complete responses,” both of which are achieved when drugs drastically reduce levels of dysfunctional blood cells in people with the disease.
The FDA has recently handed accelerated approvals to multiple myeloma drugs like Johnson & Johnson’s Tecvayli and Talvey based on the “objective response rate” — a measure of remissions determined by the presence of disease on a scan — observed in clinical testing.
But because existing treatments have gone on to achieve better outcomes for people with multiple myeloma, demonstrating a drug’s effectiveness using objective response rates “may require infeasibly large clinical trials,” the regulator said.
Minimal residual disease, by comparison, is defined as having no detectable myeloma cells using a particular type of sensitive genetic test. Complete response, meanwhile, has two definitions. One is based on reducing diseased cells, as well as eliminating tumors and biomarkers in the blood and urine. The other is a “stringent” response that includes further biomarker analysis and confirmation of no diseased cells in bone marrow.
Reaching either threshold is associated with improved long-term outcomes, the FDA said.
For drugmakers to win an accelerated approval, the FDA said it will consider either single arm or randomized trials using either minimal residual disease or complete responses as an endpoint. Randomized trials are preferred, though, because “they provide robust assessments for comparative safety,” the agency said.
The agency will still require proof of a survival benefit to convert accelerated clearances to standard ones. To get those results, drugmakers have two options. One is to continue following enrollees in an ongoing, randomized trial. The other is to follow a single-arm trial with a randomized one that measures survival.
In notes to clients this week, multiple analysts covering the developers of multiple myeloma cell therapies — such as Legend Biotech and Arcellx — wrote that the new guidelines should help speed the time it takes to gain approvals in new settings. The guidance is “a win for the field,” wrote Evercore ISI’s Cory Kasimov.
The framework is also a sign “the current FDA is not moving the regulatory bar higher,” even with Vinay Prasad, a critic of accelerated review procedures, serving as the head of the agency office regulating cell therapies, Kasimov wrote.
