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Pink Sheet — US FDA Commissioner Pushes Real-World Evidence To Guide Use Of Alzheimer’s, Obesity Drugs

Pink Sheet — US FDA Commissioner Pushes Real-World Evidence To Guide Use Of Alzheimer’s, Obesity Drugs

The “biggest area” where FDA Commissioner Rob Califf believes real-world evidence will “make a difference” is in the post-market phase, “where there are all kinds of issues that often involve other parts of the ecosystem.” He pointed to drug developers’ new focus on Alzheimer’s disease and obesity: “we’ve got these enormous markets” and significant patient need. “Do we really know exactly who should get the treatment?”

During a Friends of Cancer Research meeting on 11 September, Califf pointed specifically to Accelerated Approval as an example of where RWE can be useful: Until recently, Accelerated Approvals were mostly in cancer and rare diseases, which are often “highly segmented populations,” he said.

But now there are Accelerated Approvals in Alzheimer’s disease, and Califf feels RWE can help resolve unanswered questions. (See sidebar.)

With obesity, the products are following the traditional approval pathway, and “we know the drugs are safe and effective for the indications that were studied. But there’s a heck of a lot to be learned,” Califf continued. “Should 65% of the US population be treated with obesity drugs? I don’t know. We need to find out where the risks and benefits are actually distributed. And we’re going to have like 16 different obesity drugs, as an example. Which ones are most effective for which people?”

Califf has previously raised questions about the use of GLP-1 inhibitors to treat obesity (Novo Nordisk Pharma AG’s Wegovy and Eli Lilly and Company’s Mounjaro), noting that the data raises questions about which populations of patients should be taking those medications. (Also see “‘Anti-Aging’ R&D? One Drug To Prevent Many Diseases Is Possible, But Endpoints First Need Outside Work, FDA’s Califf Says” – Pink Sheet, 9 May, 2023.)

‘A System In Shambles’

Califf has been particularly interested in using real-world evidence in the post-approval setting, which he described as a “system in shambles.” He reiterated that “we’re not talking about the fundamental structure of drug and device approval. I think that works pretty well. We are talking about what happens after that, where FDA is only part of the system.”

Califf reiterated his view that other countries have a longer life expectancy and a better quality of life (he mentioned Singapore, specifically), “because they have organized approaches to information.” Israel uses real-time electronic health data, he noted, and the UK National Health Service enables a streamlined approach in which clinical trials are integrated directly into clinical care, “in other words, real-word evidence.”

That is a refrain that Califf has been vocalizing more often. In a commentary in Clinical Trials entitled, “Now is the time to fix the evidence generation system,” Califf writes about the stark contrast between health outcomes in the US and other countries. An evidence generation system that integrates high-quality data from a variety of sources (clinical trials, electronic health records, and wearable devices/sensors) is needed, he wrote.

He has repeatedly lamented relying on Israel for real-world data on the COVID booster doses with the emergence of new variants, promising a “very significant effort” across federal agencies to collaborate on a system to track long COVID.

At the Friends event, Califf said that “fragmentation in the clinical research ecosystem is just a reflection of our health system overall. So then you ask the question: Well, so what can we do to fix it? You could argue just ‘forget about it’, because you can’t really fix it until the health system gets fixed, but we’re going to be waiting a long time for that.”

“I would argue the health system in the US is headed the wrong direction. At some point we’re going to wake up and realize that integration of care is what matters, not each individual part sub-optimizing its own finances,” he said, pointing specifically to recent news of private equity firms purchasing cardiology clinics.

“It’s not necessarily the wrong thing to do, but it signals what’s happening is these practices then optimize their own well-being. But a patient with heart disease, particularly older people, have multiple other problems – and we have a system which is almost designed purposely not to integrate,” Califf said. “There’s lot of aggregation going on for the financial benefit of elements of that system, where does it integrate for the benefit of the patient?”

[Editor’s note: This story has been updated to clarify Califf’s remarks about the pathway for the approval pathway for obesity products.]