On the heels of FDA’s first approval of a tissue-agnostic cancer treatment, cancer research advocates are eagerly awaiting an FDA public workshop scheduled for May 9 on the scientific and regulatory issues associated with granting orphan drug designation to these therapies. The head of a major cancer think tank hopes the meeting will provide some clarity on whether these treatments, which in aggregate can treat more patients than traditional orphan drugs, will still be eligible for the designation. While the stakes are high for cancer drug developers, next week’s meeting is just the latest in a series of actions taken by FDA to update its disease definitions in the context of orphan drug designation, one industry attorney explained.
In February, FDA announced it is considering expanding the definition of certain cancers from a tissue- or organ-specific disease to a tissue-agnostic one, and is weighing whether these tissue-agnostic treatments could be eligible for orphan designation.
Orphan designation is currently available for drugs “intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug,” FDA’s website explains. Such designation carries with it seven years of exclusivity.
While each rare cancer that could be treated with a tissue-agnostic therapy may have a small enough patient population to merit orphan designation, a drug that can treat multiple types of rare cancers could expand the patient population beyond 200,000.
“In these rare cancers that are now perhaps being aggregated together based on genetic alterations rather than just the infrequently occurring site for the tumor, it may have implications to their eligibility for the orphan drug designation,” said Jeff Allen, president of Friends of Cancer Research, in an interview with Inside Health Policy.
“I think that’s one of the things that the FDA is interested in thinking through from a medical policy standpoint: How should the orphan drug designation be applied under today’s modified scientific landscape as opposed to when the designation was first developed several decades ago, and does it need to be modified?” Allen added.
Allen traced the impetus for the workshop to Keytruda, an orphan drug produced by Merck that FDA approved in 2017 for certain solid tumors with specific genetic anomalies such as microsatellite instability, he explained. It marked the first time FDA approved such a drug based on genetics rather than the location of the tumor or the type of tissue. The think tank president said the drug opened the door for a more efficient cancer drug development process to potentially take shape.
“It’s opened up the possibility for: Could it be possible for researchers to identify different cancers based on common biomarkers that could be tested together rather than running six different clinical trials?” he said. “That’s sort of in oncology the potential that I think the field is looking towards.”
However, Allen said that the new development process also opens questions for how such a process would be regulated by FDA, especially when it could expand a patient population to beyond 200,000 people.
Still, one industry lawyer said that this new development is only the latest in a long line of episodes where FDA had to redefine what constitutes a particular disease or condition for purposes of orphan designation.
“This is not uncommon, FDA has done this in other contexts before,” said Kurt Karst, attorney at Hyman, Phelps & McNamara. FDA maintains a list on its website of diseases or conditions for which the agency has modified its definition for the purposes of orphan drug designation. For example, FDA clarifies how the agency considers ovarian cancer, fallopian tube cancer and primary peritoneal cancer to be one distinct disease or condition. Likewise, the agency writes, a breast cancer that has metastasized to the brain is a distinct disease from breast cancer.
“So this is really a continuation of FDA’s always-evolving thinking on these types of issues,” Karst said
The upcoming workshop could have implications for the development of future cancer drugs. Allen said that there are plenty more Keytruda-esque products currently in development.
“There are four other PD-1 inhibitors that are on the market currently and dozens expected in the next couple years,” he said. ‘PD-1’ refers to Keytruda’s trait of inhibiting the association of certain proteins on the surface of cells. “But I don’t think it’s just isolated to PD-1 inhibitors, as there’s been a greater understanding of the immune system. This has opened up the potential for treating different types of cancers in a similar way.”