Some innovative, high-need therapies could reach the market using just Phase I clinical trials data, Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration (FDA), explained, raising the prospect of unprecedented speed to market for some drugs.
Woodcock's remarks, made at a Bloomberg-sponsored healthcare conference on 11 February 2013 and first reported by Bloomberg, pertain to the new breakthrough product designation, which was created by the FDA Safety and Innovation Act of 2012.
The pathway is intended for any 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."
That had at least some in the industry confused as to its utility, especially in regards to existing incentives such as fast-track status, priority review and accelerated approval.
Like those three expedition mechanisms, the breakthrough products designation provides a powerful incentive for companies to develop product: faster review scheduling.
The benefit, as explained by its advocates, is that novel combination therapies involving already-approved products will now be better able to obtain those faster review times, further assisting patients.
But until guidance is developed by FDA-it's in the midst of doing just that, it says-it's difficult to determine what practical benefits this designation will afford sponsors, products or patients.
In December 2012, Woodcock lauded the submission of the first breakthrough product requests.
"We're delighted now to have another tool to help expedite the development and approval of products with the 'breakthrough' designation," Woodcock wrote. "We'll continue to use our existing tools and the new 'breakthrough' authority to make our expedited drug development process even more effective, with the ultimate goal of benefiting patients with unmet medical needs."
The first sponsor would later be revealed to be Vertex Pharmaceuticals, whose cystic fibrosis drug Kalydeco (ivacaftor) was granted two designations: one for its use as a stand-alone treatment for additional forms of cystic fibrosis, and in combination with another drug (VX-809) to treat even more forms.
But Vertex, too, wasn't all that sure about the designation's benefit to its products. "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."
A Single Trial?
But now Woodcock has shed light on the agency's thinking, and potentially the upcoming draft guidance document, in regards to the breakthrough products designation.
If companies are able to conduct a single, robust Phase I clinical trial, Woodock said, a drug could very well see approval based on that data.
"We expect many of these would come available very quickly with Phase 1 data," Bloomberg reported Woodcock as saying.
At present, most trials require at least three phases of clinical trials data, and sometimes multiples of each. FDA is also increasing requirements as a condition of approval postmarketing (Phase IV) trials to follow up on issues identified or suspected in pre-market settings.
At least 12 drug products have already applied for breakthrough product designation status, Woodcock said, raising the prospect that companies will soon have a better sense of whether FDA would feel comfortable approving such a drug without the usual standards of evidence.
The plan raises a number of questions. Most obviously, can a product generate enough evidence to support an informed regulatory approval using just Phase I data, no matter how robust? FDA's recent enriched clinical trials guidance makes the case that such evidence generation is possible so long as the trial is highly targeted. Kalydeco, for example, was originally approved based on its effectiveness in those specifically with the G551D gene mutation. Narrow approvals based on trials with highly targeted patients could, in theory, mitigate many of the concerns associated with such an approval.
But other issues might also come up. For example, FDA review officials, including Bob Temple, have in the past noted that manufacturing issues could slow down such a rapid approval. The manufacturing facilities and scaled-up processes associated with a drug need to be inspected before approval, which is itself a time-intensive process.
Weighing the use of resources could come to be problematic as well. Though FDASIA included a substantial amount of new funding for FDA, none of that was specifically bookmarked for the review of breakthrough products, explained Bloomberg. If too many resources are diverted, it would come to "disadvantage" other drugs, Woodcock noted.
But difficulties aside, Woodcock observed that the benefits of such a paradigm have been eagerly noticed by industry. "It's probably going to take a while for this program to become established in the United States, but there's robust interest," she said.