FDA’s Decision-Making Process is Immune to Buyer’s Remorse
(Thursday, July 22, 2021)
Once FDA has approved a product, it almost never reverses that decision unless there are compelling safety reasons such as previously unknown life-threatening events related to the drug. FDA vigorously defends its decisions and never expresses “buyer’s remorse”. A recent case emphasized this policy when FDA rejected a petition filed by a professor at Ohio State University to withdraw approval of a drug due to the lack of efficacy of that drug in patients. The drug in question is Otsuka’s kidney disease drug tolvaptan, that was approved as a 505(b)(2) drug in 2018 for an orphan indication, autosomal dominant polycystic kidney disease (ADPKD). Otsuka also holds the original approval for tolvaptan granted in 2009 with patent protection till the year 2026. Like many recent controversial decisions, FDA approved Otsuka’s tolvaptan (trade name Jynarque) for ADPKD despite questionable efficacy data since the indication was a rare disease with no treatment options. The drug approval required Otsuka to conduct post-market studies over the next 10 years, and collect post-market safety data from patients who used the drug. Jynarque is a block-buster drug making more than $700 million for Otsuka. In its rejection of the petition, FDA stated that the petitioner had not presented any new evidence or information to support the safety risks with tolvaptan. And this is true. FDA’s adverse event database lists about 25 adverse events reported for Jynarque, and almost 5900 overall adverse event reports for the previously approved Otsuka product from 2009 (Samsca). Almost all the adverse events are expected AEs with the two drugs. FDA’s policy of holding its ground despite pressure from outside parties protects both the manufacturers and patients. Regulatory decisions are based on multi-dimensional aspects of a given product - a combination of the target indication, patient population, available data, and feasible studies. In its approval decision for Jynarque, FDA pointed to the non-feasibility of long-term clinical trials and that evidence from short-term studies indicated potential benefit to patients. While it is easy to argue that the data was limited, but the approval by FDA was based on standards established for such indications. In the last few years, FDA has been aggressive to approve drugs based on non-perfect data tacitly acknowledging that perfect data, while highly desirable, should not limit availability of critically needed drugs to patients. Ultimately, patients and their doctors should decide if they want to use a drug or not. One sentence in the approval letter for Jynarque summarizes FDA’s opinion on such approvals; “Ultimately it will be for patients to decide if tolvaptan is the drug for them”.  This unwritten FDA policy has been applied multiple times in recent years and it does not seem that the controversies have given FDA the buyer’s remorse. That said, knowing that patients’ opinions can be manipulated by advertisement campaigns, should FDA take a stricter approach to any product approval, blinded to the patients’ opinions? Depends on who you ask.

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AUTHOR               

 Dr. Mukesh Kumar
​ Founder & CEO, FDAMap

 Email: [email protected]
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