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 early promise.
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 process.
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 designation.
“Our hope is that foreign regulators will catch up,” Siegel said.
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 board.”
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 disease symptoms.
“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.