Bigger Regulatory Challenges in Diagnostics Than in Therapeutics, Industry Expert Says

For makers of cancer therapies, the regulatory environment in Europe is likely to become more like that of the United States, and the FDA may extend its reach to areas such as next-generation sequencing.

That’s what an industry expert told attendees gathered Sunday at a joint symposium of the American Society of Hematology (ASH) and the European Hematology Association, during the 56^th Annual Meeting of ASH being held at the Moscone Center in San Francisco.

David R. Parkinson, MD, of New Enterprise Associates, Inc., in Menlo Park, California, offered an industry perspective on the current regulatory climate, while Ann T. Farrell, MD, spoke on behalf of the FDA. Both Dr Farrell and Dr Parkinson spent time discussing the growing challenges in the molecular diagnostic area, an area where the FDA seeks increased oversight to ensure reliability.

As reported throughout 2014 by Evidenced-Based Oncology, a publication of The American Journal of Managed Care, the diagnostics industry has been rocked by uncertainty over reimbursement, which has caused the loss of some small companies and lawsuits. As Dr Parkinson discussed, payers began demanding evidence of clinical utility relatively recently from an industry with “no tradition” of providing such studies. Regulation of diagnostics lacks the maturity seen on the therapeutic side, Dr Parkinson said.

And yet the need to match the right drugs to the right patients—and the increased focus on smaller groups of patients and therapeutic targets—makes molecular diagnostic testing increasingly important, which demands more regulatory stability and policy solutions, he said.

Fifteen years ago, if one had suggested widespread investment by pharmaceutical companies in orphan disease, “you would have been laughed out of the room,” Dr Parkinson said. But over time, the combination of incentives created by 1983 legislation and poor returns on other investments by the drugmakers have caused the industry to look to smaller groups of patients for whom the return on investment may not be huge, but at least more certain. Collaborations with academia and more unique financial arrangements with philanthropy to manage risk have changed the playing field.

“If the field is to move forward, there needs to be investment,” he said. Without it, “treatment will not advance.”

Before Dr Parkinson spoke, Dr Farrell discussed the factors that go into FDA decision-making: essentially, regulators balance known benefits against known risks. The EMA has “exceptional circumstance, and the FDA now has an “accelerated approval” process for therapies to treat life-threatening illnesses that are superior to available treatments. FDA’s increased flexibility in the cancer area in particular has been praised. Post-marketing studies are typically needed. When it comes to orphan diseases, Dr. Farrell said the FDA aims for regular approval because the agency realizes how difficult it is to do a clinical trial in the first place.

Despite the increased flexibility, the US drug approval process is viewed worldwide as the most expensive and least certain in the world. Dr Parkinson concluded the session with a call for Congress to act to give regulators and CMS new tools, or drugs will never come down.

“All regulatory agencies are data driven,” Dr Farrell said. The data provided by drugmakers must inform product labeling to ensure safety and effectives “whether it’s a drug, a biologic, or a device.”

With an accelerated approval, the FDA wants to see evidence in the published literature, which can be based on a surrogate endpoint. The FDA will likely ask to see additional studies after approval is granted.

The agency defines clinical benefit not only as improvement in survival, Dr Farrell said, but in “how a patient feels, and how a patient functions.”

In the diagnostic area, Dr Farrell said there are 4 areas where the FDA envisions oversight in the development of companion diagnostic devices:

• The identification of patients who are likely to benefit from a therapy
• The identification of patients who are likely to be adversely affected by therapy
• Monitoring responses to treatment with therapy
• Indications and approval

Some companion diagnostics were developed in tandem with therapies, but Dr Farrell said that is not always possible, and FDA developed protocols that recognized it does not always make sense to withhold therapy just because the diagnostic is not yet available.

When ponatinib appeared for chronic myeloid leukemia, for example, FDA looked at prior approvals for imatinib, nilotinib, and dasatinib for guidance, Dr Farrell said. “We decided to approve it without reference to the test,” she said, but, “We took our post-marketing tests very seriously.”

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