During the SVB Leerink event, Woodcock said the FDA has been adapting to pharma's shift toward developing therapies for serious, difficult-to-treat diseases. “The FDA has heard from patients with these diseases that they have a willingness to assume a higher risk of uncertain efficacy and toxicity from investigational drugs and the agency has incorporated this into their review and approval decisions," the report said.
That has resulted in more flexibility on the part of the FDA, particularly when it comes to clinical trial design. Woodcock acknowledged that the “gold standard”—randomized, placebo-controlled, double-blind studies—may no longer be realistic because “many patients do not want to potentially receive a placebo,” the SVB Leerink note said. “As a result, the FDA is supportive of non-inferiority and other trial protocols, such as dose comparisons and delayed start trials.”
But what seems like good news for the drug industry and patients could backfire in more ways than one, Woodcock warned. An immediate challenge is that the Center for Biologics Evaluation and Research (CBER) might not have enough resources to handle a potential flood of new drug applications stemming from advances like gene therapy, she said.
Woodcock also noted a “wide skill gap” in the industry when it comes to preparing adequate regulatory applications. Small companies in particular lack expertise in clinical development, she said, and often push for endpoints in clinical trials like biomarker measurements that don’t really matter to patients or physicians. And companies of all sizes often fall into the trap of continuing to develop questionable drugs based on “post hoc analyses” of subsets of patients in previous trials who seemed to be responding—an exercise that often leads “to erroneous conclusions.”
The FDA’s more flexible stance towards drug development in recent years has resulted in some drugs for orphan diseases being approved for use beyond what was studied in clinical trials. During the SVB Leerink event, Woodcock said the agency is open to doing that if it’s clear the therapy’s mechanism of action could benefit a wider group of patients.
The FDA’s approvals of therapies to treat spinal muscular atrophy (SMA), Biogen’s Spinraza and Novartis’ gene therapy Zolgensma, included labels that allowed for broad use, for example. But Woodcock warned that even when the FDA is lenient with labeling, insurance companies might not follow suit.
Novartis is learning that lesson the hard way. Last week, analysts at Bernstein released a report revealing that only 11 of the 30 top insurance companies have agreed to cover Zolgensma so far, and that those companies have slapped major restrictions on the use of the $2.1 million gene therapy. Four of the insurers will not cover SMA patients who are pre-symptomatic, for example, even though the FDA approved the therapy for use in those people.
During the SVB Leerink event, Woodcock “stressed that the FDA’s philosophy and objectives are different from insurance agencies, which may restrict access to an approved drug…based on a lower value proposition,” the note said.
So what’s next for the FDA? Woodcock noted that the agency’s previously announced office on new drugs needs Congress’ approval before it can be established. But the agency intends to create a neuroscience division within that new unit, which will review drugs for psychiatric disorders, neurodegenerative disease, pain and addiction, she said. The creation of that new office is a recognition on the part of the agency that the neuroscience field will see “tremendous advances” in coming years.