In reaction to major market events over the past several months, analysts at Spherix recently captured an increasingly negative sentiment towards the US FDA – included in a new Special Topix™ report offered by the market intelligence firm. According to Paul Zimmerman, Vice President of Insights at Spherix, “As an independent voice responsible for bringing to light the experience and opinions of community physicians, we have been hearing rumblings over the past several weeks questioning recent FDA activity. We decided to survey a broader number of specialists and the results are not favorable.”
A survey of 252 specialists in dermatology, gastroenterology, nephrology, neurology, and rheumatology, fielded on July 25, revealed confidence in the FDA is swiftly dwindling. Only 36% express a high level of assurance in the agency, with nearly one-half reporting that their confidence with the FDA has eroded in the past year. Sentiment is most negative as it relates to being unbiased/apolitical, the speed of New Drug Application (NDA) reviews, and transparency with the medical community. The dissatisfaction seems to stem from unpredictable and unexpected moves from the agency, which differ by specialty.
The regulatory decision resulting in the approval of Biogen’s Aduhelm (aducanumab) for the treatment of Alzheimer’s disease, following a “no” vote by the Advisory Committee, has left neurologists especially frustrated – reflected in more than 80% stating their confidence has decreased. The approval of Aduhelm is fraught with questions regarding how involved industry was in the decision to override the Advisory Committee’s recommendation against approval.
According to one respondent, “The erosion [of my confidence] is based on the disastrously bad decision to approve aducanumab, which seems like a poorly developed and even possibly corrupt decision. I cannot remember a similar situation in which there was so much dismay and disbelief created by an FDA decision. We do not plan to use aducanumab at this time and we no longer know what to think about and how much to trust any future FDA decisions.”
Nephrologists are not far behind in their dismay and disappointment, struggling with recent events that are likely to keep two novel therapeutics, Fibrogen/AstraZeneca’s roxadustat and Ardelyx’s tenapanor, from reaching patients. Sheldon Shore, MD, a practicing nephrologist in Atlanta weighed in, “The FDA needs to work harder to help us get these new drugs approved for use in our patients. I feel it has gotten too political, making it harder and harder for new drugs to get approved.”
Despite the controversy surrounding the potential approvals, more than half of surveyed nephrologists indicate they very much want to see tenapanor approved and approximately one-third say the same for roxadustat; less than five percent are against the approval of either drug. In fact, regarding the approval of roxadustat for non-dialysis and dialysis patients with CKD-related anemia, 44% agree that they would rather see an approval contingent on a post-marketing study then a denial and requirement of additional clinical trials.
Among specialists treating autoimmune conditions, the seemingly unending scrutiny of the JAK inhibitors is raising questions about the review process the FDA is employing for several agents (AbbVie’s Rinvoq, Eli Lilly’s Olumiant, Pfizer’s abrocitinib, and Incyte’s ruxolitinib). These reviews have been extended on multiple occasions as the FDA evaluates results from ORAL Surveillance, a five-year post-marketing safety study on Pfizer’s Xeljanz ordered by the FDA when it first approved the drug for rheumatoid arthritis in 2012.
Over two-thirds of rheumatologists and dermatologists agree that the FDA should focus on each JAK individually as opposed to considering the post-marketing data from Xeljanz’s ORAL surveillance trial in relation the pending approvals of other agents within the class. One rheumatologist commented, “The delays have a negative impact on doctors and patients in the real world who are struggling to manage harmful diseases. We need direction and soon.”
Moving forward, more than 70% of all surveyed physicians agree that the FDA should establish a standard for the holding of an Advisory Committee, and approximately 40% feel that the agency should always follow the recommendations of the Advisory Committee. In the case of a split Advisory Committee decision, only 42% trust the FDA to make the final decision on a product with the patient’s best interest in mind. Additionally, many raise the question of whether the FDA’s focus on COVID-19 vaccines/treatments is causing other product approvals to be delayed and/or deprioritized.
Chris Raymond, managing director and senior research analyst at Piper Sandler, commented on recent and unexpected approval delays, “Following hundreds of drugs through all stages of development, we are finding it hard to understand how a drug that meets all primary and secondary endpoints in clinical trials – endpoints agreed to with the agency – are being denied approval. This is not the FDA we have observed in the past two decades.”
From the perspective of specialty physicians, it is not a matter of being too lax or too stringent, but rather a lack of consistency and transparency when evaluating new drugs for approval that has led to physician wariness.
