In December 2012, US Food and Drug Administration (FDA) officials had regulatory intelligence professionals and the news media in a tizzy: The agency had accepted the first two "breakthrough product designations" in the agency's history, but refused to divulge which company or companies owned the submissions, citing confidentiality procedures.
The speculation continued through much of December, with FDA staff members presumably "in the know" at various conferences fending off questions from curious questioners, saying only that two had been accepted and that other manufacturers had already expressed interest in filing applications.
That speculation has now come to an end, with Cambridge, MA-based Vertex Pharmaceuticals announcing that two of its submissions, one for Kalydeco (ivacaftor) and a combination of Kalydeco and another compound (VX-809), have been re-accepted for consideration for additional treatment indications and designated as "breakthrough products."
Kalydeco was first approved in early 2012 for the treatment of cystic fibrosis patients with a rare gene defect (the G551D mutation). The product has since been hailed by many as one of the most innovative and important new drug approvals of 2012, though its high market price raised some questions at the time.
But what does a breakthrough product designation mean, and what specifically for Vertex? It's complicated.
In a December 2012 statement announcing that FDA had accepted for review its first two breakthrough products, Janet Woodcock, director of FDA's Center for Drug Evaluation and Research (CDER) explained it thus: "A breakthrough drug is one that may offer important new benefits for patients with serious or life-threatening disease who are especially in need of new safe and effective treatments."
The designation was passed as part of the FDA Safety and Innovation Act (FDASIA) of 2012, which defined eligibility for the pathway as a product that is "intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints."
The designation opens up new incentives for companies, giving their application access to faster reviews. This is particularly important for combination therapies, as in the case of Vertex's Kalydeco/VX-809 combination therapy. Prior to the breakthrough designation, the therapy might not have been eligible for priority review status or other incentives despite its intended use.
Woodcock's statement also made clear that Vertex could be eligible for expedited collection of evidence, giving the company access to FDA review staff to assist in the design of any clinical trials done in support of the product application.
Vertex, though, said it wasn't exactly sure what the designation would mean for either it or its submission. "The implications of Breakthrough Therapy Designation cannot be determined at this time," the company said in its statement. "Vertex is working with FDA and other global regulatory agencies to determine any potential implications of the Breakthrough Therapy Designations to its ongoing and planned development activities, and subsequent regulatory submissions, for ivacaftor monotherapy and the combination regimen of VX-809 with ivacaftor."