| WASHINGTON, July 24
WASHINGTON, July 24 A new regulatory pathway
could shave years off the traditional drug approval process in
the United States, according to some companies whose drugs have
been given "breakthrough therapy" designation by the U.S. Food
and Drug Administration.
Speaking at a briefing in Washington to raise awareness of
the drug review process, Dr. Jay Siegel, head of global
regulatory affairs at Johnson & Johnson, said he expects
two years to be knocked off the time it would typically take the
FDA to review ibrutinib, the company's experimental cancer drug.
To be granted breakthrough designation, an experimental drug
must show early indication of clinical improvement over existing
therapies, even if the clinical trial is small. It might apply,
for example, to a new type of cancer drug that shows strong
J&J's ibrutinib, which it is developing with Pharmacyclics
Inc, would be the first in a class of oral medicines
that block a protein known as Bruton's tyrosine kinase. It is
being developed for patients with chronic lymphocytic
leukemia/small lymphocytic lymphoma and for patients with mantle
cell lymphoma, both cancers of the blood.
Dr. Jeffrey Leiden, the chief executive of Vertex
Pharmaceuticals Inc, who also spoke at the briefing and
whose cystic fibrosis drug Kalydeco was approved under the
designation, said his company's experience working with the FDA
was dramatically different from the normal drug approval
Under breakthrough designation, he said, "everything is on
the table" for discussion in order to move the process along as
quickly as possible. Communications that might typically take
weeks and months, under the breakthrough pathway take minutes.
"We pick up the phone and talk in real time," Leiden said.
"It makes the process immeasurably smoother."
The breakthrough pathway was spearheaded by Friends of
Cancer Research, a patient advocacy organization. It received
bipartisan support in Congress and was signed into law in July
2012. As of July 12, the FDA had received 67 requests for
breakthrough designation. It had granted 24 and denied 18.
Dr. Janet Woodcock, director of the FDA's drugs division,
said during the discussion that the breakthrough pathway was
designed to accommodate new science, particularly targeted
therapies that may work in people with certain genetic
mutations. She noted that just because the review process is
speeded up there is no guarantee of approval.
In the 1990s, she said, the agency was not seeing drugs
whose promise could be detected in early clinical trials.
"We didn't see these therapies in Phase I or II where you
said 'bingo,' you've got a likely winner," she said.
Still, there are challenges associated with speeding up a
drug's development timeline. For one thing, other nations might
not be willing to approve the products based on the FDA's more
flexible clinical trial standards under the breakthrough
"Our hope is that foreign regulators will catch up," Siegel
Moreover, he said, it is not clear that insurers will pay
for drugs if the data do not show improved survival or other
clear benefit they are used to seeing when drugs are approved.
One task, he said is to figure out "how to bring payors on
The panelists did not discuss what happens once a drug
reaches the market under the breakthrough designation.
Under a separate pathway known as "accelerated approval"
drugs may be approved based on a so-called surrogate endpoint -
a measure, such as tumor shrinkage - that might reasonably be
expected to confer a clinical benefit such as improved survival.
Companies that win approval for a product under the
accelerated approval process are required subsequently to prove
through further clinical trials that the surrogate measure does
in fact correlate with improved survival or a reduction in
"A discussion on this topic is reckless if it doesn't
discuss the next stage after the drug reaches the market," said
Sidney Wolfe, co-founder and senior adviser to Public Citizen's
Health Research Group, a watchdog organization that has
frequently criticized the FDA for approving, or failing to
withdraw, drugs it considers unsafe.
Woodcock said the FDA is now working to develop a mechanism
to speed the development of breakthrough diagnostics that can be
used in conjunction with new drugs to help identify which
patients will respond to a particular therapy.